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DIGESTIVE PROTEASES FROM THE STOMACHLESS CUNNER FlSH (TAUTOGOLABRUS ADSPERSUS): PREPARATION AND USE AS FOOD PROCESSING AID BY MARY ABENA KYEl A Thesis subrnitted to the Faculty of Graduate Studies and Research in partial fulfilment of the requirements for the degree of Master of Science Department of Food Science and Agricultural Chemistry Macdonald Campus of McGill University Montreal, Canada January, 1997 O Mary A.Kyei, 1997.

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Page 1: DIGESTIVE PROTEASES FROM THE STOMACHLESS CUNNER … · 2005-02-09 · DIGESTIVE PROTEASES FROM THE STOMACHLESS CUNNER FlSH (TAUTOGOLABRUS ADSPERSUS): PREPARATION AND USE AS FOOD PROCESSING

DIGESTIVE PROTEASES FROM THE STOMACHLESS CUNNER FlSH (TAUTOGOLABRUS ADSPERSUS): PREPARATION AND USE AS FOOD

PROCESSING AID

BY

MARY ABENA KYEl

A Thesis subrnitted to the Faculty of Graduate Studies and Research in partial fulfilment of the requirements for the degree of Master of Science

Department of Food Science and Agricultural Chemistry Macdonald Campus of McGill University

Montreal, Canada

January, 1997

O Mary A.Kyei, 1997.

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The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantid extracts Fom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation.

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ABSTRACT

Digestive proteases were isolated from the pancreas of the stomachless

cunner fish (Tautogolabrus adspersus) and characterized in terms of their

physicochemical properties, their ability to hydrolyze native pectin

methylesterase (PME) from orange and polyphenol oxidases (PPO) from

mushroom and the ability of the cunner enzyme(s) to maintain the stability of

orange juice cloud.

Optimization of the steps used for the preparation of the proteases

resulted in an increase in specific activity from 0.55 to 2.04 unitslrng (i.e. from the

crude to the trypsin fraction), a purity of 3.7 fold and a yield of 1.4 %. The

ammonium sulfate, acetone and trypsin fractions showed good stability when

stored for four weeks on ice and -20°C, with observed specific activity decreasing

in the order trypsin fraction, acetone fraction, and ammonium sulfate fractions.

The trypsin fraction had two protein bands with pl in the ranges of 6.24-6.83 and

9.66-10.25. The molecular weights of the 2 proteases were 24,000 and 14,400

@ kDA respectively. The 24,000 kDA protease was described as trypsin and the

14,000 kDA protease as trypsin-like, based on their action on the synthetic

substrate BAPNA. The cunner trypsin had 220 amino acid residues with a

relatively low basic amino acid content. Soybean trypsin inhibitor (SBTI)

competitively inhibited the cunner trypsin with V,,, ranges of 1.39 ic 0.001 to 1.42

k 0.002, and Km values of 0.99 f 0.002 to 4.94 i 0.040 mM. The K, values

decreased from 3.48 to 3.3 x IO ' mM. Aprotinin showed a mixed type of

inhibition, with V,, decreasing from 0.74 k 0.037 to 0.42 t 0.051 unitslminlmg

and Km also decreased from 1.81 f 0.23 to 0.3 f 0.10 mM. The K, values also

decreased from 13.7 k 0.001 to 1.9 k 0.003 x 10' mM. Furthermore, the cunner

trypsin exhibited a type 3 Km dependence on temperature, suggesting that the

affinity of the enzyme for its substrate was highest at 10°C which coincides with

the habitat temperature of cunner.

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a The cunner trypsin fraction exhibited exceptional capacity to hydrolyze

native proteins versus the bovine trypsin. Incubation of native PME with cunner

or bovine trypsin resulted in a loss of 75% or 35% in PME activity respectively.

Similarly, a 75% or 55 % loss in PPO activity was observed after treatment with

cunner and bovine trypsin respectively. Bovine trypsin, however, hydrolyzed the

heat-denatured PME and PPO better than the cunner trypsin. Also, there was no

reactivation of both PME and PPO activity after treatment with either the cunner

or bovine enzyme during storage at 4 O C for 3 weeks. However, PPO retained up

to 20% or 50% of the initial activity after treatment with cunner or bovine trypsin,

respectively.

A 3 x 3 factorial design involving the factors of temperature, enzyme

concentration and incubation time carried out gave an r' of 0.92 and 0.95 for

cunner and bovine trypsin treated PME respectively. On the other hand, an r' of

0.91 and 0.94 was obtained for the combined effects using cunner and bovine

trypsin for PPO inactivation. Validation of the mode1 of PME inactivation

measured as the % cloud remaining revealed that the cunner trypsin fraction

upheld the cloud stability of cloud juice better than bovine trypsin, with cunner

trypsin retaining more than 90% of the cloud whereas the juice treated with

bovine trypsin only resulted in a 70% retention of the juice cloud.

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RÉSUMÉ

Des protéases digestives ont été extraites du pancréas d'un poisson, la

tanche-tautogue (Tautogolabrus adspersus) et caractérisées en termes de leurs

propriétés physico-chimiques, de leur capacité à hydrolyser des pectine-

methylestérases natives d'oranges et des polyphénol oxydases de champignons

et de leur capacité a maintenir la turbidité d'un jus d'orange.

Les différentes étapes du protocole utilisé pour la préparation des

protéases ont permis une augmentation de I'activité spécifique de 0,55 à 2'04

unitéshg (de l'extrait brut a la fraction trypsine), un taux de purification de 3,7 et

un rendement de 1,4%. Les fractions sulfate d'ammonium, acétone et trypsine

ont montré une bonne stabilité pendant quatre semaines de conservation a - 20°C, l'activité spécifique diminuant le plus dans la fraction trypsine, puis dans la

fraction acétone et enfin dans les fractions sulfate permettait d'ammonium. La

fraction trypsine possède deux bandes de protéines avec des pl de 6,24-6,83 et

9,66-10'25. Les poids moléculaires des deux protéases sont respectivement de

0 24.000 et 14.400 kDa. La protéase de 24.000 kDa a été décrite comme une

trypsine alors que celle de 14.400 kDa comme étant de type trypsine, en se

basant sur leur action sur le substrat synthétique BAPNA. La trypsine de la

tanche-tautogue comprend 220 résidus d'acides aminés avec une teneur en

acides aminés basiques relativement faible. L'inhibiteur de la trypsine de soja

(SBTI) a inhibé de façon compétitive la trypsine de la tanche-tautogue avec des

V,,, compris entre 1,39 + 0,001 et 1,42 I 0,002. et des valeurs de Km comprises

entre 0,99 + 0,002 et 4'94 t 0,040 mM. Les valeurs de Ki ont diminué de 3,48 a

3,3 x 10-4 mM. L'aprotinine a démontré une inhibition de type mixte, avec un V,,,

diminuant de 0,74 k 0,037 à 0,42 k 0,051 unitéslminlmg et un Km diminuant de

1'81 + 0,23 à 0'3 +_ 0,10 mM. Les valeurs de Ki ont également chuté de 13,7 k

0,001 à 1,9 I 0,003 x 10-3 mM. De plus, la trypsine de la tanche-tautogue a

démontré une dépendance à la température de type 3 Km, ceci suggérant que

a l'affinité de l'enzyme pour son substrat est plus élevée à 10°C et coïncidant avec

la température d'habitat de la tanche-tautogue

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0 La fraction trypsine de la tanche-tautogue a montré une capacité

exceptionnelle d'hydrolyse de protéines natives en comparaison de la trypsine

bovine. L'incubation de PME native avec la trypsine de la tanche-tautogue ou la

trypsine bovine s'est soldée, respectivement, par une perte de 75% ou 35 % de

I'activité de la PME. De même, une perte de 75% ou 55 % de l'activité de la PPO

a été observée apres traitement avec la trypsine de la tanche-tautogue et la

trypsine bovine, respectivement. Cependant, l'hydrolyse de la PME et la PPO

dénaturées par la chaleur a été meilleure par l'action de la trypsine bovine que

celle de la trypsine de la tanche-tautogue. De plus, il n'y a pas eu de réactivation

des activités de la PME et de la PPO après traitement avec la trypsine de la

tanche-tautogue ou la trypsine bovine et après conditionnement à 4°C pendant 3

semaines. Cependant, la PPO a retenu 20 % ou 50% de son activité initiale,

respectivement, après traitement avec la trypsine de la tanche-tautogue ou la

trypsine bovine.

Un modèle factoriel de type 3x3 incluant les facteurs de température, de

a concentration de l'enzyme et du temps d'incubation mis en oeuvre a donné,

respectivement, un de 0,92 et de 0'95 pour la PME traitée avec trypsine de la

tanche-tautogue et la trypsine bovine. D'autre part, un ? de 0.91 et de 0,94 a été

obtenu par les effets combinés de la trysine de la tanche-tautogue et de la

trypsine bovine pour l'inactivation de la PPO. La validation du modèle

d'inactivation de la PME mesurée comme le pourcentage de turbidité restante a

révélé que la fraction trypsine de la tanche-tautogue de maintenir la turbidité

d'un jus plus efficacement que la trypsine bovine, avec la trypsine de la tanche-

tautogue retenant plus de 90% de la turbidité alors que le jus traité avec la

trypsine bovine ne retenait que 70% de la turbidité.

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ACKNOWLEDGEMENTS

I would like to express my sincere gratitude to my supervisor Dr. B. K.

Simpson for his guidance, patience, encouragement in various manner,

assistance and invaluable advice throughout the course of this study.

I wish to also acknowledge the assistance of Mr. Benny Gibbs in the

amino acid analysis, to Dr. 1. Alli (Chair of Food Science Department), Ms Lise

Stiebel, Ms Barbara Laplaine, and to al1 the staff of the Food Science

Department. I also express my sincere thanks to my colleagues, Mr. Amaral

Sequeira, Ms Luzette Teruel, Mr. Victor Awafo and Mr. Farag Eltaib, for their

help and advice any time I called on them. I also want to thank al1 the students of

Food Science Department for creating an atmosphere conducive for both

studying and socializing. For supporting me financially, I would like to thank ... I would like to thank the following for their friendship, and also making a home

away from home for me: Dr. and Mrs. 1. N. A. Ashie, Mr. and Dr. (Mrs.) F.

Yeboah, Dr. and Mrs. S. Aggrey, Dr. and Mrs. G. B. Awuah, Mrs. Eva Yapo, Ms

Wigdan Madani, Mr. and Mrs. S. Chimpango, Mr. and Mrs. R. Molenaar, Mr. and

Mrs. V. Awafo, Ms Ramon Sareevoravitkul, Mr. Michael Owusu-Manu and Mr.

Virgil Mensah Dartey.

I would like to deeply thank my husband, Mr. Nana Kwesi Agyepong, for his love,

enormous support, assistance and patience during rny absence from home. i

also appreciate deeply my parents, Mr. and Mrs. Kyei and my brothers and

sisters, my parents-in-law Mr. and Mrs. Agyepong and family for their support

love and unceasing prayers.

Above all, I am extremely grateful to the Lord God Almighty for strength and

comfort during my long stay away from my family.

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vii

TABLE OF CONTENTS

. . ........................................................................................................... ABSTRACT II .............................................................................................................. RÉSUMÉ iv

................................................................................... ACKNOWLEDGEMENTS vi ........................................................................................ TABLE OF CONTENT vii

LIST OF FIGURES .............................................................................................. x ... .............................................................................................. LIST OF TABLES XIII

LIST OF ABBREVIATIONS .............................................................................. xiv

.......................................................................................... I INTRODUCTION 1

.................................. 2.1 Endogenous and exogenous enzymes in food processing 3 ................................................................................. 2.1.1 Endogenous enzymes 3

....................................................................................... 2.2 Exogenous enzymes 3 ...................................................................................... 2.2.1 Microbial sources 5

............................................................................................ 2.2.2 Plant sources 5 ......................................................................................... 2.2.3 Animal sources 7

2.3 Marine enzymes ................................................................................................... 7 ..................................................... 2.3.1 Trypsin(ogen)s from the marine sources 10

. . . .

2.3.2. Trypsin from the stomachless cunner ..................................... 2.3.2. Hydrolysis of native and denatured proteins ..........................

.......................................................... 2.3.3: Comparative biochemistry 2.3.4: Applications and potential applications of marine enzymes ir

.......................................................... ............................... industry .. 2.4 Pectin methylesterase and the citrus juice industry ......................

................... IO

..........S........ 12

................... 13 the food ................... 16 ................... 19

.......................................... 2.4.1 .Pectins. the substrate of pectin methylesterase 20 2.4.2. Citrus juices. pectin and cloud stability ...................................................... 21

...................................................................... 2.4.3. Methods of PME inactivation 22 O .................................................................. (a) Thermal inactivation (90-1 15 C) 22

(b) Low pH inactivation of PME ......................................................................... 23 .............................. (c) Supercritical carbon dioxide (Coq) inactivation of PME 23

............................................................ (d) High pressure inactivation of PME 2 4 (e) Degradation of PME substrates using pectinase ......................................... 24 (9 Use of PME inhibitors ................................................................................... 24

................................................ (g) Inactivation of PME by proteolytic enzymes 25 ...................................... 2.5 Polyphenol oxidases (PPO) and enzymatic browning 26

2.5 Inactivation of polyphenol oxidases (PPO) .................................................... 27 ..................................................................................... (a) Thermal inactivation 28

(b) Reducing agents .......................................................................................... 28 .......................................................................................... (c) Chelating agents 29

............................................................................................. (d) PPO in hibitors -29

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viii

(e) Oxygen exclusion ........................................................................................ 30 ............................................................................................ 2.6. Rationale for study 30

....................................................................................................... 2.7. 0 bjectives 3 2

................................................................... I II MATERIALS AND METHODS 33 .......................................................................................... 3.1 Biological specimen: 33

............................................................................................................ 3.2 Reagents 33 ...................................................................................................... 3.3 Methodology 3 4

.......................................................... 3.3.1 Recovery and purification of trypsin : 3 4 ................................................................................................ 3.3.2 Enzyme assay 3 5

....................................................................................... 3.3.2.1 Amidase activity 3 5 3.4 Protein determination ......................................................................................... 36

............................................................ 3.5 SDS polyacrylamide gel electrophoresis 36 ............................................................................................. 3.5.1 Casting of gels 37

.............. 3.5.2 Sample preparation and SDS polyacrylamide gel electrophoresis 37 ................................................................ 3.5.6 Molecular weight determinations -40

............................................................................................. 3.6 lsoelectric focusing 41 ...................................................................................... 3.6.8 Fraction screening -43

........................................................................................... 3.6.7 Refractionation -43 ....................................................................... 3.7 Amino acid composition analysis 43

............................................................................................... 3.8 Inhibition studies -45 ..................................................... 3.8 Pectin methylesterase activity determination 46 ...................................................... 3.8.1 Effect of cunner trypsin on PME activity 47

......................................... 3.8.2 Effects of cunner trypsins on heat-treated PME 47 ............................................................................. 3.9 PPO activity determination 47

.................................................................. 3.9.1 Effect of cunner on PPO activity 48 3.9.2 Effect of cunner trypsin on heat-treated PPO activity .................................. 48

................................................... 3.10.1 Optimization studies 1 experimental design 48 .................................................................................... 3.10.2 Statistical analysis 49

............................................................................. 3.11 . 1 Treatment of orange juice 49 3.1 1.2 pH measurements ..................................................................................... 51

................................................................. 3.1 1.3 Storage of treated orange juice 51

................................................................ IV RESULTS AND DISCUSSIONS 52 ............................................................................. 4.1.1 Recovery of trypsin fraction 52

4.1.2 Elution profile of the trypsin fraction on SBTI-Sepharose Affinity media ...... 52 .......................................................... 4.1.3 Electrophoresis of the trypsin fraction 52

4.1.4 Stability of Various Fractions at Different Storage Temperatures ................ 58 .................................................... 4.1.5 lsoelectric focusing of the trypsin fraction 58

................................................................. 4.1.6 Amino acid composition analysis 62 .................................................... 4.2 The Effect of Inhibitors on the trypsin fraction 65

.................................................................. 4.3. Dependence of Y, on Temperature 68 4.4 Effects of trypsins on Native PME and PPO ...................................................... 73

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........................................ 4.5 Effects of trypsins on heat-denatured PME and PPO 79 4.6. Reactivation studies of trypsin-treated PME and PPO ...................................... 83 4.7 Combined effect of [E]/[S] ratio. incubation time and temperature on PME and PPO ................................................................................................................... 86

................................................................................................. 4.8 Model Validation 95

V CONCLUSIONS ............................................................................................................................................. 98

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LIST OF FIGURES

Flgure Title

Calibration curve for protein content determination using the enhanced lowry method and bovine serurn albumin (BSA) as standard.

Elution Profile of the acetone fraction on SBTI-Sepharose Affinity media.

Calibration curve for molecular weight determination for SDS-PAGE electrophoresis.

SDS-PAGE gel showing the migration of the proteins

Effect of storage temperature on the stability of the ammonium sulfate, acetone and trypsin fractions, (a) storage on ice and (b) storage at -20°C

(a) Fractionation and (b) Refractionation of the trypsin fraction after isoelectric focusing at 4 O C on Biorad Rotofor System

Chromatogram of amino acid standards at 570 nm using norleucine as interna1 standard

Effect of increasing BAPNA concentration on s bti-ln hibition. (a ) cunner trypsin and (b) bovine trypsin

Effects of increasing BAPNA concentration on aprotinin inhibition. (a) cunner trypsin and (b) bovine trypsin

Lineweaver-Burk plots for the trypsins using SBTl as inhibitor. (a) bovine trypsin and (b) cunner trypsin, with 1 mM BAPNA (pH 8.2) as substrate

Lineweaver-Burk plot for the trypsins using aprotinin as inhibitor. (a) bovine trypsin and (b) cunner trypsin with 1 mM BAPNA (pH 8.2) as substrate

Dependence of cunner trypsin Km on temperature.

Calibration curve for PME activity assay

Page

54

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Effect of cunner and bovine trypsins on native PME activity using an [E]/[S] ratio 0.5 and (a) 0.35% and (b) 0.5% pectin solutions.

Effect of cunner and bovine trypsins on native PME activity using an [E]I[S] ratio of 1 and (a) 0.35% and (b) 0.5% pectin solutions

Effect of cunner and bovine trypsins on native PME activity using an [E]/[S] ratio of 2 and (a) 0.35% and (b) 0.5% pectin solutions

Effect of cunner and bovine trypsins on native PPO activity, using 5 mM DOPA as substrate at 25°C

(a) Effect of heat treatment on PME activity and the effect of cunner and bovine trypsins on heat-denatured PME at (b) 50°C and (c) 55°C.

(a) Effect of heat treatment on PPO activity and the effect of cunner and bovine trypsins on heat-denatured PPO ai (b) 40°C and (c) 50°C.

Reactivation studies of trypsin treated PME with (a)cunner and (b) bovine.The substrate was 0.5 % pectin at 25°C. The storage studies were carried out at 4°C.

Reactivation studies of trypsin treated PPO at 4"C, using 5 mM DOPA (pH 6.5) as substrate.

Three dimensional response surface plots showing the effects of [cunner trypsin]/[S], incubation time and temperature, on PME activity. (a) effect of temperature and [E]/[S] ratio at constant time (2.5h) (b) effect of [E]I[S] ratio and time at constant temperature (25°C) and (c) effect of time and temperature at a constant [E]/[S] ratio (1).

Three dimensional response surface plots showing the effects of [bovine trypsin]l[S] ratio, incubation time and temperature, on PME activity. (a) effect of temperature and [E]/[S] ratio at constant time (2.5h) (b) effect of [E]/[S] ratio and time at constant temperature (25°C) and (c) effect of tima and temperature at a constant [E]/[S] (1).

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xii

@ 4.24 Three dimensional response surface plots showing the 93 effects of [cunner trypsin]/[S] ratio, incubation time and temperature, on PPO activity. (a) effect of temperature and [E]I[S] ratio at constant time (2.5h), (b) effect of [E]/[S] ratio and time at constant temperature (25°C) and (c) effect of time and temperature at a constant [E]/[S] ratio (1).

4.25 Three dimensional response surface plots showing the 94 effects of [bovine trypsin]l[S] ratio incubation time and temperature, on PPO activity. (a) Effect of temperature and [E]/[S] ratio at constant time (2.5h), (b) effect of [E]/[S] ratio and time at constant temperature (25°C) and (c) effect of tirne and temperature at a constant [E]/[S] ratio (1).

4.26 (a) An [E]I[S] ratio of 0.3 and 1.5 bovine and cunner trypsin 96 at 35" for 1.3 and 0.4 h respectively and (b) [E]/[S] ratio of 1.5 and 0.9 of bovine and cunner trypsin at 15°C for 2.5 h. The juice were stored at 4OC

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. . . X l l l

LIST OF TABLES

Table Title

Examples of some endogenous enzymes and their effects

Examples of Microbial Enzymes used in Food Processing

Examples of plant enzymes used in food processing

Some examples of animal enzymes used in food

processing

Some examples of animal enzymes used in food

processing

Hydrolysis of protein substrates by cunner enzymes

Relative Activities of Trypsins from various sources

Formulations of SDS PAGE Resolving Gel

Formulations of SDS-PAGE stacking Gel

Solutions for running electrophoresis and staining Gets

Program for amino acid analysis on Beckman HPLC

System 6300

Values of coded Ievels in Experimental design

Recovery of trypsin from the pancreas of the cunner fish

One-way ANOVA of storage at O OC and -20 OC

Amino acid composition of trypsin fraction

Kinetic data on SBTl and aprotinin inhibition of cunner and

bovine trypsin

Parameter Estimates for percent PME and PPO

inactivation

Page

4

6

8

9

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xiv

4 8 0

Ala

ANOVA

Arg

Asn

A ~ P BAPNA

BSA

CYS

dA/min

DOPA

Gln

Glu

G ~ Y

H is

IIE

KDa

Ki

Kr" Leu

LYS

Met

MPa

Phe

PME

PPO

Pro

R f

S BTl

LIST OF ABBREVIATIONS

Absorbance at 280 nm

Alanine

Analysis of variance

Arginine

Asparagine

Aspartic acid

N-a-Benzoyl-arginine-p-nitroanilide

Bovine serum alburnin

Cystein

Change in absorbance pet- minute

Dihydroxyphenylalanine

Glutamine

Glutamic acid

Glycine

Histidine

lsoleucine

Kilodaltons

Inhibitor dissociation constant

Substrate affinity constant

Leucine

Lysine

Methionine

Megapascal

Phenylanine

Pectin methylesterase

Polyphenol oxidase

Proline

Mobility

Soybean trypsin inhibitor

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a PAGE

Ser

TAME

Thr

T ~ P

TY r Val

v m a x

Polyacrylamide gel electrophoresis

Serine

Tosylargine methyl ester

Threonine

Tryptophan

Tyrosine

Valine

Maximum velocity

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CHAPTER 1

INTRODUCTION

Enzymes have been used to accomplish specific desirable changes in foods, for centuries. In brewing, malted barley have been used for starch conversions, the addition of saliva to starchy products in preparing fermented liquors, and the tenderization of meat by wrapping it in bruised leaves of papaya tree to tenderize it are a few examples of ancient use of enzymes (Whitaker, 1994). These techniques were handed down from generation to generation without complete understanding of the reactions and changes involved. Sorne of these traditional practices have been refined to the present-day uses of enzymes like chymosin, a-amylase, and papain in the food industry (Simpson and Haard,

their 1987a). The importance of enzymes in food processing has resulted in the more recent application of irnmobilized enzyme systems to the processing of foods and the production of food and chemical ingredients (Whitaker, 1994).

I ) Examples of some of the applications of immobilized enzyme technology are (a) immobilization of a-galactosidase used in the hydrolysis of raffinose in sugar

beet juice which hinders crystallization of sucrose in sucrose production (Reilly, 1980), and (b) the production of fructose from glucose using immobilized glucose isomerase (Burke, 1980).

Also with the advent of genetic engineering, a wider range of enzymes will become available on a larger scale and thus increase the scope of enzyme technoiogy (Price and Stevens, 1985). In genetically engineered enzymes, one or two aspects of the enzyme are improved and include (i) modification of the effect of pH andlor heat on the stability, (ii) altering the temperature andlor pH optimum, (iii) adjusting the substrate specificity and binding efficiency, (iv) increasing the resistance to solvents, or inhibitors, and (v) modifying the enzyme to catalyze an aitogether new reaction. Examples of applications of genetically engineered enzymes in food processing are (i) improving the quality of tomatoes by modifications of the enzymes polygalacturonase and PME. The modifications lowers the production of these enzymes in tomatoes. The modification also helps

O to improve the appearance of tomato paste made from the engineered tomato (Schuch, 1994), (ii) the production of genetically engineered acetolacetate decarboxylase for use in reducing the maturation time in brewing (Dornenburg

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a and Lang-Hinricks, 1994) and (iii) the production of chymosin, which is used in the curdling of milk, by cloning the eukaryotic gene into microorganism so that the enzyme can be produced by normal fermentation (Dornenburg and Lang- Hinricks, 1994).

Enzymes have remarkable catalytic properties, especially when compared with other catalysts. The advantages include high catalytic activity under mild conditions of pH and temperature, high specificity, thus obviating undesirable side reactions. lndustrial catalysts lack this specificity of reaction, which precludes their use for modifying specific components of food systems. In addition, enzymes are natural and non-toxic substances, they are active at low concentrations. Furthermore, the rate of the reaction catalyzed by the enzymes can be controlled by adjusting the temperature, pH and the amount of enzyme employed, and they can be inactivated after use. These features of enzymes make them highly desirable for use as processing aids for various industrial products. In recent years they have been exploited on an increasing scale in food, pharmaceutical and chemical industries (Richardson and Hyslop, 1985).

Enzymes are widely distributed in biological systems and the main

a sources of enzymes used in food processing are from plants, animais and microorganisms. In plants, the enzymes are distributed in the latex, fruits, leaves, seed, flower, rhizome, sprouts and Sap of the plant (Macdonald et al., 1993; Robinson and Dry, 1992; Rillo et al., 1992; Seymour et al., 1991; Wicker and Temelli, 1988; Schwimmer, 1983). In animal sources, the enzymes are distributed mainly in the stomach, oral tissues, the pancreatic tissues, intestines, liver and the muscles. Other underutilized animal source is the protease-rich fish offal which often pose a disposa1 and pollution problem (Simpson et al. 1991; Schwimmer, 1981). In microbial sources the type of microorganism and the type of media is a prerequisite for the type of enzyme to be produced.

Homologous (anaiogous) enzymes from different sources and species exhibit different physical, chemical and biochemical properties. These properties include temperature optimum and stability, pH optimum and stability. These in turn affect the catalytic efficiency and thereby its applicability as food processing aid for a particular industrial bioconversion. In some conversions, a high temperature stability is of benefit, e.g., the production of corn-syrups, the step of

O the conversion of dextrins to glucose by glucoamylase, an enzyme with a high temperature stability is advantageous and makes the selection of rnicrobial glucoamylases beneficial over those from other sources (Spradlin, 1989).

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CHAPTER II

2.1 ENDOGENOUS AND EXOGENOUS ENZYMES IN FOOD PROCESSING

2.1 .l ENDOGENOUS ENZYMES

Foods are complex biological materials, and as such subject to a wide variety of modifying agents. Among these are microorganisms that cause undesirable spoilage or beneficial fermentation, endogenous biochemicals that undergo such changes as autoxoidation, and endogenous enzymes that cause nurnerous desirable and undesirable changes (Richardson and Hysslop, 1 985). Majority of food-related enzymes can either improve or impair food quality depending on the extent of enzyme action on (i) the food material, (ii) the processing, or (iii) the final product, as well as such variables as time,

0 temperature, pH, and past history of the food (Schwimmer, 1981). Examples of some endogenous enzymes and their effects on foods are shown in Table 2.1

2.2 EXOGENOUS ENZYMES

There are three main sources of enzymes used in food processing, namely microorganisms, plants and animals. The greatest variety of industrial enzymes are presently derived from microbiat sources, with lesser diversity coming from plant and animal sources (Godfrey and Reichelt, 1983). The group of enzymes that find the most use in industry is proteolytic enzymes. Proteases from various sources differ in their catalytic and physical properties, and whether

a particular enzyme would be suitable for use in a particular industrial application depends on several factors such as the type of transformation desired and the nutritional constituents of the food material. For many uses, the specificity of the

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Table 2.1 : Examples of sorne endogenous enzymes and their effects.

Enzyme Desirable Effect Undesirable Effect Pectic enzymes

Cathepsins

Phenolases

Lipoxygenases

Peroxidases

Firmness of green beans

Liquefaction of fish tissues in fish saucelpaste manufacture Developrnent of color in tea

Bleaching of hard wheat flour; lmprovement of the texture wheat flour doughs.

Degradation of H,O, and other peroxides in foods

Loss of juice cloud in orange juice Postharvest spoilage and textural changes in fresh fruits and vegeta bles

Postrnortem deterioration of muscle foods.

Enzymic browning of fruits vegetables such as apples, banana potatoes, and crustacean species such as shrimp

Destruction of vitamin A and provitamin A, carotenoids pigments, and essential polyunsaturated fatty acids Production of off-flavors in frozen vegetables and in stored cereals.

Oxidative destruction of vitamin C, bleaching of carotenoids and anthocyanins

Adapted from Richardson and Hysslop, 1985

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9 Protease is of paramount importance (Simpson and Haard, 1987a), especially

when it is desired to modify a single component during food processing.

2.2.1 MlCROBlAL SOURCES

Microbial enzymes are obtained from non-pathogenic, non-toxigenic cultures and also those cultures that do not produce anti-biotics. Microbial enzymes form the greatest proportion of the food grade enzymes because the source microorganisms are very versatile, for example, they can be altered by

mutation or genetic engineering to produce a greater quantity or a different enzyme; the recovery of enzymes is often very easy since many microbial enzymes are extracellular; there are readily available, and rnicroorganisms have a very high rate of enzyme production.

lnspite of the potential diversity that can be achieved by use of microbial enzymes, only few species of microorganism have been extensively evaluated and approved as safe for use to produce industrial enzymes. The reason for this being the high cost of getting a microorganism approved by regulatory authorities

a (Simpson and Haard, 1987). Table 2.2 shows a list of some microbial enzymes used in food processing and their sources.

2.2.2 PLANT SOURCES

By far the two major sources of enzymes from higher plants used in food processing are the green papaya melon for the preparation of products rich in proteolytic enzymes, and germinated barley, malt, which contains starch- digesting enzymes used in brewing and to some extent as an adjunct in breadmaking. Minor sources include pineapples and figs.

The main plant sources of enzymes in the food industry are listed in Table 2.3.

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Table 2.2: Examples of Microbial Enzymes used in Food Processing Enzyme Source Food Use

Carbohvdrases a-amylases Aspergillus niger; In baking and brewing

Bacillus subtillus indus t ry P-amylases Bacillus polymyxa In baking and brewing

industry Glucoamylases Aspergillus oryzae In preparation of thinned

Rhizopus oryzae starches

Cellulases

lnvertase

Trichoderma reesei In complex enzyme systems for oil extraction

Saccharomycetes Formation of invert sugar and in confectionery industries

Pectinases Aspergillus niger Fruit juice and wine Rhizopus oryzae industries

Proteases Fungal Proteases Aspergillus niger In the baking and the dairy

Aspergillus oryzae indu stries

9 Bacterial Proteases Bacillus subtilis In the baking industry Baccillus lich formis

Rennets Mucor mehei In cheese production Mucor pusillus

Esterase Lipases Aspergillus niger Lipid hydrolysis in fish oil

Aspergillus oryzae concentrate Oxidoreductases

Catalase Aspergillus niger Rernoval of H202 from milk Micrococcus and egg white lysodeikticus

Glucose oxidases Aspergillus niger desug aring of eggs

lsomerase Glucose isomerase Actinoplanes preparation of high fructose

missouriensis corn syrup Bacillus coagulans

Adapted from Richardson and Hysslop, (1 985)

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2.2.3 ANIMAL SOURCES

Various animals have been used traditionally as sources of enzymes for food and the biornedical industry. The best known food enzyme obtained from animals is rennin (EC 3.4.4.3) found in the stomachs of calves (Taylor, 1991).

The hydrolytic activity of digestive enzymes derived from organs such as the stomach or pancreas has important consequence for the food industry (Yamamoto, 1975). Animal enzymes used in food processing are mainly proteolytic in nature. Proteolytic enzymes obtained from livestock offal currently do not adequately meet the demand on world basis, and the future availability of

traditional enzyme sources is dependent on the political and agricultural policies

that control the production of iivestock for slaughter (Godfrey and Reichelt,

1983). Moreover, traditional animal enzymes have been restricted to few species

namely bovine and porcine offal (Simpson and Haard, i987a). Table 2.4 shows some examples of animal enzymes used in food processing and their sources.

According to Simpson et al. (1991), microbial enzymes that have replaced animallplant enzymes may exhibit certain subtle differences in some properties which render them less suitable for a process application, as in the case of the use of micrabial proteases in cheese making. It has been reported that sornetimes there is increase in curd hardness, acidity development and drainage of the whey when M. meihei is used (Schwimmer, 1985).

2.3 MARINE ENZYMES

Enzymes from marine organisms rnay also be utilized as food processing

aids. Since animals cary out essentially the same types of metabolism, it is to be expected that different organisms such as fish, shellfish, marnmals, birds or reptiles will contain the same functional classes of enzymes (Simpson et al.

1991). Some fish enzymes such as the digestive proteases, pepsin(ogen)s,

trypsin(ogen)s and chymotrypsin(ogen)s, have been extensively studied.

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Table 2.3: Examples of plant enzymes used in food processing

Enzyme Source Food Uses Carbohvdrases

a-amylases Barley malt

Wheat Barley wheat Barley malt

Proteases

m Bromelain Pineapples, Amas cosmosus,

Ficin Figs, Ficus sp. Papain Papaya, Carica papaya

Oxidoreductases

In brewing and distilling industries In baking and brewing industries In brewing industries and in coffee making

In the meat industry, brewing; fats and oils industries and in protein modification

Lipoxygenases Soybean flour In baking industry

Adapted from Richardson and Hysslop, (1 985)

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Table 2.4: Sorne examples of animal enzymes used in food processing

Enzvme Source Food Uses - - ... . -. - .

Proteases Pepsin Porcine or other animal In dairy as rennet

stomachs extenders; production of

Trypsin protein hydrolysates

Animal Pancreas In the dairy industry; production of protein hydrolysates

Rennets Fourth stomach of In cheese production ruminants

Esterases Lipases Edible stomach; animal, In flavor development in

pancreatic tissues cheese Oxidoreductases

Catalase Bovine liver Removal of H202, Cold sterilization of milk

Adapted from Richardson and Hysslop, (1 985)

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2.3.1 TRYPSIN(0GEN)S FROM THE MARINE SOURCES

Trypsinogens have been recovered from digestive tract of several fish

species and some exarnples are shown in Table 2.5 . The fish trypsins thus far isolated and characterized include those from

fish species with a functionally distinct stomach. Exarnples include rainbow trout, Salmo gairdenerri, (Kiarnikado and Taichino, 1960); the chinook salrnon, Oncorhynchus tshawytcha, (Croston, 1965); Green chromide, Etropplus suratensis (Sundara and Sarma, 1960) Atlantic cod, Gadus morrhua, (Overnel, 1973); sardine, Sardinus rnelanostica (Murakami and Noda, 1981); Arctic capelin, Mallotus viliosus (Hjemeland and Raa, 1982); African lungfish,

Protopterus cuthiopicus, (de Haen et al., 1977); catfish, Parasilurus asotus,

(Yoshinda et al., 1984) and Greenland cod, Gadus agac (Simpson and Haard,

1984a).Trypsins have also been characterized from fish species without a

functionally distinct stomach, include crayfïsh, Astacus flavatillis, (Pfleiderer et

al., 1967); bonefish, Carasuis auratus gibello (Jany, 1976); cunner,

Tautogolabrus adpsersus (Simpson and Haard, 1985); crawfish, Cambrus virillis and mullet, Mugii cephalus, (Jeong et al. 1994).

2.3.2: TRYPSIN FROM THE STOMACHLESS CUNNER

Cunner, Tautogolabrus adsperus, is one of the group of fishes with no morphologically or physiologically distinct stornach (Chao, 1973). Other group of stomachless fish are the bonefish, Carassuis auratus gibello (Jany, 1976) and

crayfish, Astacus flaviatilis (Pfleiderer et al., 1967). The lack of stomach is a

phylogenetic characteristic of the family and is not related to the feeding habits of

the species.

A trypsin fraction was isolated from the pancreas of cunner and shown to contain two different enzymes, which were classified as trypsin (rnolecular weight of 24,000 kDa) and trypsin-like (molecular weight 14,000 kDa) (Simpson and Haard, 1985). The specific activities for the trypsin fraction, trypsin and trypsin- like enzymes were found to be 1.54, 1.21 and 0.58 respectively.

The trypsin fraction from cunner exhibited two pH optima of 7.0 and 8.5

and a maximum and minimum range of stability were 2-3 and 6-7 respectively

(Simpson and Haard, 1985)

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Table 2.5: Trypin(ogen)s from selected marine species

Fish Source Tissue Reference Sardine, (Sardinus melanostica)

Goldfis h (Carassuis auratus)

Capelin (Mallotus villosus)

Caîfis h ( Parasilurus asotus)

Rain bow trout, (Salmo gairdenerri) Chinook salmon, (Oncorhynchus tshawytcha)

Green chromide (Etropplus suratensis)

African lungfish, (Protopterus cuthiopicus)

Atlantic cod (Gadus rnorhua),

Greenland cod (Gadus ogac)

Cunner, (Tautogolabrus adsperus)

Crayfis h (Astacus flaviatilis)

Crawfis h (Cambrus virillis)

Mullet (Mugii cephalus)

Pyloric ceca

Intestinelhepatopancreas

Digestive track

Pancreas

Digestive tract

Pyloric ceca

Digestive tract

Pancreas

Pyloric ceca/messentries

Pancreas

Cardiac fluid

Hepatopancreas

Pyloric ceca

Murakami and Noda, 1981

Jany, 1976

Hjerneland and Raa, 1982 Yoshinda et al., 1984

Kitamando and Taichino, 1960 Croston, 1 965

Sundara and Sarma, 1960

de Haen et al., 1977

Overnel, 1973

Simpson and Haard, l984a Simpson and Haard, 1985

Pfleiderer et al., 1967

Jeong et al., 1994

Jeong et al., 1994

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The temperature optimum of the trypsin fraction was reported as 450C The enzyme was found to possess unusual thermal stability, retaining more than

75% of its activity after heating at 80% for 1 hr and more than 50% of its activity after 30 min. at 1000C (Simpson and Haard, 1987). In this aspect, trypsins from cunner were more heat stable than trypsins from other fish species thus far characterized, which tended to be readily inactivated by temperatures as Iow as 40-50oC (Simpson and Haard, 1984a; Hjelmeland and Raa, 1982; Murakami and

Nada, 1981). The activation energy for the hydrolysis of DL-BAPNA by the trypsin and

trypsin-like enzyme from cunner, were found to be 1791Jlmol and 2054JImol respectively (Simpson and Haard, 1985). These values are comparable to those

reported for Greenland cod (Simpson and Haard, 1984a) but much lower than those of mammalian trypsins, e.g., 3153JImol for bovine trypsin (Simpson and Haard, 1984b).

2.3.2. HYDROLYSIS OF NATIVE AND DENATURED PROTEINS

The stomach is known to aid protein digestion in several ways, notably by

its secretion of stomach acid and acid proteases that denature and initiate

hydrolysis of proteins. Thus stomachless fish like cunner, are deprived of the

acid denaturation and acid proteolysis which takes place in the stomach,

expected to make proteins in food more amenable to subsequent degradation in

the intestines by trypsin, chymotrypsin and other proteases (Simpson et al., 1991). However, trypsins from stomachless fish, such as crayfish (Pfleiderer et al., l967), cunner (Simpson and Haard, l987b) and the crawfish (Jeong et al., 1994) have been reported to be more capable of hydrolyzing native ribonuclease A, lactate dehydrogenase, and hemoglobin as compared with trypsins and chyrnotrypsin from higher vertebrates with a functional stomach, (Simpson and

Haard, 1987; Mihalyi, 1978; Jany, 1976). Simpson and Haard (1984b) reported that bovine trypsin hydrolyzed

native hemoglobin only 18% and ribonuclease A 20 % as fast as their denatured

a counterparts, while the rate at which cunner trypsin hydrolyzed the same

proteins was 58 or 40% compared to its hydrolysis of the denatured forms of the

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a protein substrates (Table 2.6). Approximately 12% of RNase activity was lost with bovine trypsin, while the cunner trypsin and the trypsin-like enzyme

destroyed about 58% and 72% respectively of RNAse activity, after 4 hr

incubation at 23%. Similar findings were made with a trypsin-like enzyme from

the stornachless crayfish (Pleiderer et al., 1967) as summarized in Table 2.6.

A comparison of the rates of hydrolysis of the native versus denatured

proteins of trypsins from various sources in terms of their relative activities showed that cunner trypsin appears to be have a higher relative activity for al1 the substrates with the exception of casein (Simpson et al. 1989).

2.3.3: COMPAMTIVE BIOCHEMISTRY

Marine enzymes in general and cunner trypsin in particular are similar in

8 many ways to their mammalian counterparts. Generally their pH-activity profiles,

substrate specificities, molecular weight, and response to inhibitors or activators

resemble those from mamrnalian counterparts (Simpson and Haard, 1989; Tanji

et al., 1 988; Squires et al., 1986).

However the digestive proteases from marine sources differ from their

mammalian counterparts in certain respects namely

(i) they are less stable under acid conditions

(ii) they have a higher catalytic activity

(iii) they are generally more heat-labile

(iv) they are more stable at cold temperatures

(v) they hydrolyze (undenatured) proteins to a greater extent (Simpson et al., 1991 ; Tanji et al. 1988; Ramaskrishna et al., 9987;

Simpson and Haard, 1984)

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Table 2.6 Hydrolysis of protein substrates by cunner enzymes

Enzyme Su bstrate initial rate of DH, %

hydro lysisa

Bovine trypsin hernoglobin 0.73 0.96

Cunner trypsin 1.24 0.95

Trypsin - like 0.43 2.53

Bovine trypsin UT- hernoglobinb 4.02 2.83

Cunner trypsin 2.14 1.68

Trypsin - like 1 .O5 5.50

Bovine trypsin ribonuclease . 0.25 0.60

Cunner trypsin 0.67 7.22

Trypsin - like 0.46 2.50

Bovine trypsin HT-ribonucleasec 1.27 7 -41

Cunner trypsin 1.69 1.29

Trypsin - like 0.85 3.72

aln milliequivalents/min per micromole enzyme; b Urea-denatured hemoglobin

CHeat-denatured ribonuclease. Adapted from Simpson and Haard, (1 987b)

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Table 2.7: Relative Activities of Trypsins from various sources

% Relative Activity

Source BAPNA TAME Casein RNasea Hemoglobin

Greenland cod 64.5 96.1 77.4 ndb ndb

Atlantic cod 68.5 1 O0 85.5 40.3 52.4

Cunner 1 O0 91.0 82.2 I O 0 1 O0

Bovine 48.8 81.5 1 O0 37.3 58.9

a Undenatured substrates ; Not determined; Data from Simpson et al., (1989)

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2.3.4: APPLICATIONS AND POTENTIAL APPLICATIONS OF MARINE ENZYMES IN THE FOOD INDUSTRY

The application of an enzyme as a food processing aid in an industrial

conversion depends on its catalytic efkiency and physical properties (Godfrey

and Reichelt, 1983, Richardson and Hysslop, 1985). Furtherrnore, in order to use

a particular enzyme as a food processing aid it should confer sorne commercial

benefiîs (Taylor, 1991). The effectiveness of an enzyme for a given industrial

conversion is species dependent as analogous enzymes from different

sources/species display a varied catalytic activity and physical properties.

Digestive proteolytic enzymes utilized in the food industry have been

obtained froin the livestock offal of bovine and porcine (Simpson and Haard,

e 1987) and the stomachs of suckling calves (Schwimmer, 1981). In general,

animals are a poor source of enzymes and animal production lacks the flexibility

if enzyme production needs to be suddenly increased or decreased (Taylor,

1991). This has led to the development of microbially derived alternatives,

making microorganisrns source for greater variety of industrial enzymes. lnspite

of the potential that can be achieved by the use of microbial enzymes, very few

of the species are used to produce industrial enzymes due to the stringent

evaluation required for a microorganism to be regarded as safe and the

substantial cost involved in getting microorganism approved (Godfrey and

Reichelt, 1983).

An alternative animal source for enzyme production is the fish offal.

However, few attempts have been made to recover enzymes from these

sources. Apart from being a very good source for nutrients, the fish offal is also a

very good source for enzymes (Simpson et al. 1991). The underutilization of this

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a rich enzyme source is of concern because according to Simpson and Haard,

(1991), only about half of the fish offal produced are converted into products of

economical importance such as fish meal. The rest serve as disposal and

pollution problem. As with a typical animal source for enzyme production, the use

of fish offal as source for industrial enzymes is limited by fluctuations in

availability due to seasonal harvest. The enzymes from the fish offal can be used

to augment the production of enzymes from animal sources, as well as make use

of their unique property of having a high rnolecular activity at low ternperatures.

Also, the fish offal can be turned into a proper economic use thereby reducing

disposal /pollution problems associated with the fish offal.

To date, there are few marine enzymes that are used on a commercial

scale. The following are a few examples:

(i) lcelandic Fisheries Laboratories use trypsin-like enzymes from cod viscera for

a the removal of skins, membranes and scales from fish and production of fish

gelatin from fish skins and scales (Raa, 1989).

(ii) In Nonnray pepsin from cod viscera is used for the hydrolysis of fish frames to

produce marine peptones for subsequent use in microbiological media

preparations (Almas, 1989) and incorporation in fish feeds for the production of

immune stimulants for fish reared in captivity (Raa, 1989).

The laboratory scale applications are as follows:

Fish enzymes have been used to prepare various cheeses. Rennin or

chymosin (EC 3.4.4.3) is the enzyme traditionally used in cheese rnaking. This

enzyme converts the colloidal milk casein into a curd giving high yields of cheese

and desirable proteolysis in the aged cheese. The source of this enzyme has

been the abomassum of suckling calves (Schwimmer, 1983). There is increasing

O concern about the decreasing supply of rennin from the calves. Moreover, the

slaughter of young calves is economically wasteful (Taylor, 1991). Most

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e proteases are inferior to chymosin for cheese production. This is due to their

broader specificities for protein substrates, which leads to excessive proteolysis

during curdling and subsequent steps in the cheese making operations. Such

activities lead to inadequate yield of curd, unacceptable rheological properties of

the cheese, and off-flavor (de Koning, 1978). According to Berridge (1951),

however, nearly al1 proteolytic enzymes will clot milk under appropriate

conditions.

Studies by Brewer et al., (1984) have shown that it is possible to prepare

a satisfactory cheddar cheese with Atlantic cod pepsin as the rennet agent.

However, when the conventional cheddar cheese process was employed, there

was loss of some fat and proteins to the whey fraction indicating that additional

protein degradation occurs during curd formation and the early stage of

cheddaring. The high molecular activity of fish pepsins at low temperatures also

I ) occurs when milk is treated to initiate the clotting process. The enzymic phase of

milk clotting, involving hydrolysis of the phenylalanine-methionine bond of K-

casein, can be separated from the non enzymic phase, ii-ivolving transformation

of sol to gel, by carrying out the process at a temperature below 10°C. Cold

renneting of milk with a catalyst having a low temperature coefficient for the

enzyme, can be accomplished with lower enzyme concentration, thereby

conserving rennet and minimizing the presence of residual curd pepsin. Utilizing

the temperature stability of the cod pepsin, the temperature of milk treated with

the enzyme can be increased to 39°C after the enzymic phase at 0°C to cause

the inactivation of the enzyme (Simpson and Haard, 1987a).

Bovine trypsin is capable of preventing the copper induced-oxidized flavor

in milk (Lim and Shipe, 1972). Greenland cod trypsin has also been shown to be

effective in preventing oxidized flavor in milk (Simpson and Haard, 1984~).

While Greenland cod trypsin is thermally unstable, the high thermal stability of

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a bovine trypsin allows it to survive the pasteurization treatment used and this

helps to prevent the subsequent hydrolysis of milk proteins.

Greenland cod trypsin was used to accelerate the fermentation of

herrings, and was able to achieve greater solubilization of fish protein and

sensory score of the fish sauce during low temperature fermentation than bovine

trypsin (Simpson and Haard, 1984~).

Trypsin from Atlantic cod was used to facilitate the extraction

carotenoproteins from crustacean shells (Cano-Lopez et a/., 1987). The fish

enzyme recovered more pigment (64 %) and protein (81%) in the complex than

bovine trypsin (49 % pigment and 68 % protein).

The applications and the potential applications of the proteases from the marine

sources are thus many and diverse. As reported in Table 1, there are several

@ endogenous enzymes like the pectic enzymes which causes destruction of cloud

stability in fruit juices (e.g. citrus and tomato) as well as postharvest texture

softening in fresh fruits and vegetables; and polyphenol oxidases which causes

enzymic browning of fruits and vegetables such, as apples, banana, potatoes

and crustacean species such as the shrimp. The financial losses due the effect

of these endogenous enzymes are enormous and several methods to control

their effect have been investigated.

2.4 PECTIN METHYLESTERASE AND THE CITRUS JUlCE INDUSTRY

Pectin methylesterase (PME), (E.C. 3.1.1.1 1) causes loss in cloud stability

a of citrus juices by releasing pectyl methyl esters from pectin (Chaplin and Bucke,

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a 1990). PME has been reported to operate in a sequential manner with

polygalacturonase (E.C.3.2.1.5) (Dahodwala et al., 1974).

PME from mandarin orange has been described as a single glycosylated

polypeptide with molecular weight of 37000. Although this enzyme exhibited ad a

pH optimum of 9.0, it has been shown to be active at pH's below pH 5.50. Such

studies observed a Km of 0.84rnglml and a V,, 0.38pmol of galacturonic acid

produced /min for hydrolysis of pectin.

Mandarin PME retained about 50% of its activity after heating at 62OC for

1 min with the activity decreasing to 20% at 70'~. At 9U°C the activity is

undetectable (Rillo et al., 1992).

2.4.1: PECTINS, THE SUBSTRATE OF PECTIN METHYLESTERASE

Chemically, pectins are polymers of galacturonic acid linked by a,?-4

glycosidic linkages into long chains (Schwimrner, 1981).

Pectins have been classified as

(i) pectic substances, Le., material comprising al1 polygalacturonic acid

containing substances; (ii) protopectin, Le., water insoluble materials in bound

form that yield pectins upon hydrolysis; (iii) pectins, i.e., partly esterified

polygalacturonic acids (generally rnethyl esters) further divided into low rnethoxy

and high methoxy pectins depending on whether they contain less or more than

7% methoxy-esterified polygalacturonic acids; and (iv) pectinic acids which have

al1 carboxyl groups in the free form and are water insoluble (Fellers, 1991).

The solubility of pectins increase with increasing esterification and

decreases with size. The usefulness of pectins stems mainly from their capacity a

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to form stable gels or films, and to increase the viscosity of acidified sugar

solutions (Pomeranz and Meloan, 1987).

2.4.2: CITRUS JUICES, PECTIN AND CLOUD STABILITY

Fresh citrus juice, like orange juice, contains finely divided particulates in

a suspension, that give it a 'cloudy' appearance. Analysis has shown that this

particulate material is composed almost exclusively of pectin, protein and lipid

(Baker and Breummer, 1972). When this stable colloidal system collapses, the

juice separates into a clear liquid and solid sediment. Once converted to an

unattractive two-phase system of a flocculant sedirnent in a clear serum, the

I) juice looses its consumer appeal (Castaldo et al., 1991) since cloud stability is a

most important quality attribute of orange juice (Balaban et al., 1991). In addition,

the cloud contains most of the characteristic orange flavor and color. During

citrus processing, large juice vesicles (sacs) are ruptured to release the juice

(Bradock and Marcy, 1987) and large juice vesicles are removed during the

finishing operation as a secondary product of juice processing. Juice vesicles,

referred to as pulp have unique physical and chemical properties and are used

in non juice drink bases and juice containing beverages (Braddock and Marcy,

1 987).

Multiple forms of PME are reported to be associated with cell fractions of

peel, rag and juice sacs from citrus fruits (Versteeg et al., 1980). PME therefore

enters the juice from the pulp during extraction and deesterifies pectin to

a produce low methoxy pectins (Castoldo et al., 1991). The product, pectinic acid

chelates with monovalent and divalent ions (e.g., ~ a + and Ca++) present in the

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juice to form insoluble calcium pectates, which precipitates along with cloud

particles resulting in clarification of juice cloud (Versteeg et al., 1980).

2.4.3: METHODS OF PME INACTIVATION

The cloud of citrus juice has been stabilized by protecting pectin from

PME (Owusu-Yaw et al., 1988). Several technological approaches have been

used to solve the problem of juice clarification. These approaches include:

(A) THERMAL INACTIVATION (90-1 1 5 ' ~ )

This is the most common method in PME inactivation (Wicker and Temelli,

1988; Veersteg et al., 1980; Eagerman and Rouse, 1976). Heat treatments

however, affects aroma and flavor (Balaban et al., 1991) and causes

development of a brown color due to non-enzymatic browning reactions to affect

the quality of the single strength orange juice (Nurniki and Hayashi, 1983). The

extent or severity of the heat treatment was found to be highly dependent on the

total soluble solids and increasing total soluble solids resulted in less

inactivation. Severe heat treatment of foods is known to induce racemization of

amino acids and proteins (Gandolfi et al., 1994) and instantaneous heating and

cooling is difficult to achieve (Cohen et al., 1994). Thus there is the potential for

losses of heat-labile components of the juice by heat treatrnents. Wicker and

Temelli (1988) indicated the difficulty in obtaining a logarithmic fold reduction in

a PME activity, and for industrial purpose there is the necessity of introducing

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tubular heat exchangers of relatively large diameter, and the addition of water to

enhance pumpability and reduce disruptions in continuous process.

(B) LOW pH INACTIVATION OF PME

This method is based on the fact that PME from orange has less activity

at pH 5.5 than at their optima pH of 9.0 or close to that (Rillo et a/., 1992;

Versteeg, 1980; 1978). In this method, pH 5 2.0 is used in conjunction with low

temperature storage. Very little cloud loss was observed at 40C in orange juice at

pH 2.0, however, with this method there was a major destruction of (> 95%) of

vitamin C (Owusu-Yaw et al., 1988). Moreover, the addition of HCI or the use of

cation exchange resins to lower the pH of the juice resulted in unacceptable juice

quality (Balaban et a/., 1991).

(C) SUPERCRITICAL CARBON DlOXlDE (COp) INACTIVATION OF PME

PME may be inactivated with supercritical CO2 below temperatures

necessary for thermal inactivation. This treatment is reported to be based on the

hypotheses that at high pressures, COn dissolves in water, producing carbonic

acid, thereby lowering the pH temporarily and inactivating PME. On returning the

pressure to atmospheric, COn would be separated from the juice and the pH

restored to the original value. This treatrnent combines the effect of low pH and

high pressure in the inactivation process. There is a problem of enzyme

reactivation with this treatment (Balaban et a/., 1991) and this rnay cause loss of

cloud stability during storage. Supercritical treatment conditions employed in this

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a treatment range between 7-34 MPa with corresponding temperatures of 35-60°C

(Arreola et al., 1991 ).

(D) HlGH PRESSURE INACTIVATION OF PME

High pressures of about 500 MPa for a treatment period of 10 min partially

inactivate PME. This treatment is highly dependent on the soluble solids content.

At pressures up to 600 MPa, pulp particle size distribution was slightly changed

after treatment at room temperature for 30 min (Takahashi et al., 1993) Higher

soluble solid content is known to protect PME from inactivation (Ogawa et al.,

1990). In addition, complete inactivation was not possible at any pressure Ievel

used, and the

a (Ogawa et al.,

sta bility.

problem of enzyme reactivation during storage was observed

1990), which may subsequently contribute to the Ioss in cloud

(E) DEGRADATION OF PME SUBSTRATES USlNG PECTINASE

In this method, soluble pectin is degraded to a low degree of rnethylation

with enzymes such as pectin lyase or polygalacturonase that prevent pectin

precipitation by calcium through reduction of pectin size. This method has found

limited application (Castaldo et al., 1991) as there are potential problems of

enzymic flavor deterioration (Baker and Breummer, 1972)

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(F) USE OF PME INHIBITORS.

A glycoprotein isolated from the kiwi fruits is known to be a powerful

enzyme inhibitor (Balesteri et al., 1990) and is capable of inactivating PME from

orange juice and other fruit juices (Castaldo et a/., 1990). The activity of the

inhibitor was found to be dependent on the amount of soluble solids. Above a

certain minimum soluble solids content, a decrease in cloud stability was

observed (Castaldo et al. 1991).

(G) INACTIVATION OF PME BY PROTEOLYTIC ENZYMES.

It has been reported that the cloud in citrus beverages could be stabilized

by subjecting pasteurized concentrate to one or more enzymes with protease

activity and that the cloud stability depended on the degree of protein hydrolysis

in the juice (Castaldo et al. 1991).

In al1 the methods reported so far, the amount of total soluble solids

tended to be the determining factor in the success of the inactivation procedure

employed. In addition, there was the possibility of enzyme reactivation when the

inhibiting effect was removed. In other cases involving the use of low pH,

although no cloud loss was reported, there was a loss of almost al1 the vitamin C

contained in the juice.

The possibility of using a combination of proteolytic and pectinases

(Castaldo et al., 1990; Baker and Breummer, 1972) precludes the effect of the

amount of total soluble solids, which tends to be the major determining factor in

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a most of the methods reported. The cloud stability depends on the degree of

enzyme hydrolysis in the juice.

Alternatively, the unique ability of digestive proteases from the

stomachless cunner to inactivate native protein molecules may be exploited to

inactivate PME and thereby achieve cloud stability in citrus and other fruit juices.

The trypsin from cunner may be utilized in combination with other

treatments like low temperature and1 or low pressure to aid in the inactivation of

PME, and thereby stabilize the juice cloud of selected fruit juices, as well as to

preserve heat labile components in the juice.

2.5 POLYPHENOL OXIDASES (PPO) AND ENZYMATIC BROWNING

PPO (EC.1.10.3.1) has several names depending on the type of substrate

used in the enzymatic conversion viz. tyrosinase, cathecol oxidase, cresolase,

polyphenolase, cathecolase and phenolase, (Whitaker, 1994). PPO is widely

distributed in biological systems and have been isolated from several fruits, e.g.

apples (Sapers et al., 1989) banana, kiwi (Park and Luh, 1985), grapes (Valero

et al., 1988), pears (Zhou and Feng, 1991) and avocado (Kahn, 1983);

vegetables, such as spinach leaves (Katoh et al., 1989); mushrooms (Golan-

Goldhirsh and Whitaker, 1984); crustacean species (Chen et al., 1993) and

potato (Friedman and Bautista, 1995).

PPO causes undesirable browning reactions in fruits, vegetables and

crustacean species (Chen et al., 1993; Valero et al., 1988). The browning

reactions observed during postharvest storage or processing fruits, vegetables

and crustacean species is a widespread phenornenon (Zhou and Feng, 1991)

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a and its net only cornmercially undesirable, but it has been considered to

generally affect food quality from both sensory and nutritional point of view

(Rouet-Mayer et al., 1993).

PPO, a multifunctional copper-containing protein, is known to catalyze the

orthohydroxylation of monophenols to o-diphenols, and the subsequent oxidation

of O-diphenols to O-quinones. The quinones so formed react with themselves

protein or amino acids to give characteristic brown pigments (Valero et al. 1992;

Garcia-Gomona et al., 1988)

The characteristics of PPO Vary as the type of substrates available. The

temperature optimum of PPO range from 35°C in airen grapes (Valero et al.,

1988) to 45°C for phenolase-DOPA in shrimp (Simpson et al., 1987). The

temperature stability range from 35°C to 75°C in kiwifruit (Park and Luh, 1985).

The pH optimum for the different PPO range from as low as 3.5 in airen grapes

@ (Valero et al., 1988) to 7.5 in shrimp (Chen et al., 1993). Most of the PPOs are

reported to be stable in the alkaline pH regions (- 8.0) and less stable in acid pH

range.

There are several PPO substrates and the specific substrate requirernent

differs markedly depending on the source. The main PPO substrate is tyrosine

(Richardson and I-lyslop, 1985). The other substrates are di- or tri- phenolic

compounds like cathechol, d-cathecin, chlorogenic acid and Dopa and

rnonophenolic compounds are pcresol and pcoumaric acid (Whitaker, 1994).

2.5 INACTIVATION OF POLYPHENOL OXIDASES (PPO)

Several methods have been employed for PPO inactivation. They include:

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(A) THERMAL INACTIVATION

Thermal inactivation of PPO consists of a treatment behveen 80-90°C for

6 S. Although the process is swift, there is a considerable loss in flavor, loss of

solids due to leaching, weakened texture of products like prepeeled potato and

even the possibility of non-enzymic browning (Schwimmer, 1981).

(B) REDUCJNG AGENTS

The reducing agents normally used in PPO inactivation include ascorbate,

bisulfites and thiols. Sulfites are the rnost commonly used reducing agents.

Thiols, sulfites and ascorbate act in a complex way by reacting with the quinones

4) formed by enzymatic reactions and reducing them back to their O-diphenolic

compounds and other colorless complex (Walker, 1975; Golan-Goldhirsh and

Whitaker, 1984). In addition, the enzyme is known to loose activity in the

presence of sulfites by direct suicide inactivation of the enzyme (Golan-Goldhirsh

and Whitaker, 1984). Thiols are reported to directly affect PPO by displacing the

histidine ligated to the copper due to the high affinity of the thiols for copper. This

results in modifications of the active sites and therefore inactivation (Friedman

and Bautista, 1995). However, because of the greater awareness of its possible

damaging effect to the health especially in asthmatics (Friedman and Bautista,

1995) reduction or its complete elimination is one of the highest priority (Valero

et al., 1992). Equally good alternatives to sulfites are being investigated.

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(C) CHELATING AGENTS

Several chelating agents have been used to inhibit enzymatic browning.

These agents are known to cause inhibition by interacting with copper on the

prosthetic group (Sapers et al., 1989). Examples of such agents are cyanide,

diethyldithiocarbamate, azide, EDTA, an acidic polyphosphate (sporix), and

copper-metallothionein (Goetghebeur and Kermasha, 1996; Sapers et al., 1989;

Simpson et al., 1987). De pletion of the agents, however, causes browning.

(D) PPO INHIBITORS

Among several chernicals proven to inhibit PPO activity, sorbic acid, kojic

O acid and some aromatic carboxylic acids of the benzoic, cinnarnic and

phenylalkanoic series have been widely studied and proven to be effective

inhibitors of PPO of various origins (Janovitz-Klapp et al., 1990; Gunata at al.,

1987; Simpson et al., 1987). These inhibitors act by the binding of both the

neutral and dissociated forms of the acids to the free and cornplexed enzymes

causing the inhibition (Billaud et al., 1996). However, in the application of these

inhibitors, the degree of inhibition is highly dependent on the pH of the medium

since the form of inhibitor (free or dissociated) which acts best is pH dependent.

In addition, Sapers et al. (1989) have reported the possibility of large proportions

of benzoic acid inducing browning by stimuiating the hydroxylation of cinnamic

acid to p-coumaric acid, a PPO inhibitor which can be further hydroxylated to

give caffeic acid, a substrate of PPO.

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(E) OXYGEN EXCLUSION

An atmosphere modified with carbon dioxide (CO,) has been used to

inactivate several enzymes including PPO (Arreola et al., 1991; Chen et al.,

1993). This treatment is effective in inactivating lobster PPO and the combination

on heat and carbon dioxide treatment resulted in further loss of PPO activity.

Carbon dioxide affects PPO by the acidification of the environment, leading to

the inactivation of PPO (Chen et al., 1993)

Many chemicals have been extensively studied for the inactivation of

PPO. Although large proportions of these chemicals show effectiveness in

inhibiting PPO activity in fruits vegetables and crustaceans, several problems

plague their successful application. These include their toxicity, off-flavor the

e possibility of the chemicals re-inducing browning and above al1 the economic

feasibility of such an inactivation procedure. An alternative method to inactivate

PPO may be the use of digestive proteases from stomachless marine organism

as the cunner. The digestive proteases are naturally occurring compounds and

their use in food application would meet with less resistance from consumers.

This alternative may also serve to preserve the flavor lost during thermal

inactivation of PPO and maybe lower the cost of the operation, in that the source

of these enzymes are from the fish waste (offal).

2.6: RATIONALE FOR STUDY

Traditionally, digestive proteolytic enzymes have been derived from

bovine and porcine offal, whereas a greater diversity of the industrial enzymes

are obtained from microbial sources (Godfrey and Reichelt, 1983).

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Fish offal is known to be a good source of nutrients (e.g., proteins, fat,

and vitamins) and useful biochemicals (e.g., enzymes, pigments, flavorants),

which may be recovered and used as food ingredients or processing aids.

Proteases from fish so far isolated have been reported to have several unique

advantages over the proteases of the mammals from land. As a result of their

low temperature stability, some of them have the ability to hydrolyze native

proteins better, and give high turnover rate at low temperatures

In addition to curtailing the problem of pollution posed by the disposal of

the fish offaf, the offal of the fish can be put into a better economic use by

extracting the digestive enzymes and utilizing the unique properties of these

enzymes in the inactivation of some problematic enzymes such as PME and

PPO. Several inactivation procedures have been utilized to control the effect of

PME in fruit juices, and PPO in vegetables, fruits and crustacean species. These

a include thermal inactivation, low pH, high pressure, use of chemicals and several

protein inhibitors. In addition to the operating costs involved in the running of

thermal heat exchangers and high pressure systems, these methods of

inactivation influence the final product by affecting the final flavor since they

affect the heat-labile essential components responsible for the flavor. In addition

to the effects on heat-labile components, there is also the possibiiity of non-

enzymic browning. With some of the methods, the appearance of the products,

is comprornised as the particles are affected by the extent of the treatment, as in

the pressure treatments.

Certain chernicals such as sulfites are not permitted in foods beyond their

effective limits due to safety concerns. Lowering the pH below certain levels can

also create problems in the food systems, for example in orange juice al1 the

@ vitamin C present in the juice is destroyed.

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An inactivation procedure where the PME and PPO are directly

hydrolyzed by digestive enzymes from marine sources, will not only lower the

operating costs involved in inactivating these enzymes but will also preserve the

heat-labile flavor components. The use of trypsins from the stomachless cunner

could be one such approach for inactivation of PME and PPO. In addition,

trypsins are naturally occurring components of food systems and will appeal to

consumers over the chernical additives.

Although there have been relatively few attempts to use fish enzymes

such as cunner trypsin as industrial processing aids, their effectiveness for

hydrolysis at low temperatures warrants more attention in exploiting such

properties.

2.7: OBJECTIVES

The overall objectives of this research are

(i) to extract and purify, ttypsin from the pancreas of the cunner fish,

(ii) to evaluate the effectiveness of cunner trypsin(s) to inactivate PME andlor

PPO and

(iii) to determine the effect of storage conditions on certain quality attributes of

single strength orange juice treated with the trypsin from cunner.

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CHAPTER III

MATERIALS AND METHODS

Live cunner fish, Tautogolabrus adspersus, were held in tanks in the

laboratory between 5-10 OC and fed with capelin fish until needed. The fish were

killed by severing the cervical vertebra and the pancreatic tissue was removed

and rapidly frozen in liquid nitrogen and kept at -80 O C prior to extraction.

Orange juice: Orange juice (Tropicana) was bought from the local grocery

shop.

3.2 REAGENTS

Trichloroacetic acid (TCA), Folin-Ciocalteu's phenol reagent, acrylamide,

Coomaasie brilliant blue (R250), citric acid, pectinesterase (citrus), bovine

trypsin, soybean trypsin inhibitor, aprotinin, bovine serum albumin, cyanogen

bromide activated sepharose 4B, ammonium sulfate, N,N,N1,N'-tetra methyl

ethylenediamine (TEMED), phosphoric acid, dihydroxyphenylalanine (DOPA)

and bromophenol blue were purchased from Sigma Chemical Company (St.

Louis).

N, N' methylene-bis-acrylamide, glycine, tris(hydroxymethyl)

aminomethane, sucrose, urea, sodium dodecyl sulfate, 2-mercaptoethanol were

purchased from Biorad (Montreal)

aB Galacturonic acid and pectin (citrus), were purchased from ICN

Biomedicals (Toronto)

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Bromothymol blue and acetone were obtained from ACP ( Montreal)

Sodium acetate, isopropanol, sodium hydroxide and sodium chloride

were obtained from BDH (Quebec)

Acetic acid, ether, dimethyl sulfoxide (DMSO), sulfuric acid (H2S04),

potassium phosphate monobasic, and potassium phosphate dibasic were

purchased from Anachemia (Quebec)

Hydrochloric acid and Brij 35 (enzyme grade) were purchased from Fisher

Scientific (Toronto)

Electrophoresis calibration kit (low molecular weight) was purchased from

Pharmacia (Montreal).

3.3 METHODOLOGY

3.3.1 RECOVERY AND PURIFICATION OF TRYPSIN :

Trypsin fraction from cunner pancreas was prepared according to the

method described by Simpson and Haard (1985).

The pancreatic tissue was rapidly frozen in liquid nitrogen and comminuted into

powder using a waring blender. About l o g of the powder was stirred in 0.05M

Tris-HCI buffer (5 mllg) pH 7.8 containing 0.5M NaCl and 0.02M CaC12 at 4 OC

for 3 hours, after which the resultant mixture was centrifuged at 3000g for 30

min. at 4 OC. The supernatant was made up to 0.2% with Brij 35 and stirred

overnight at 4 OC. It was then centrifuged at 10,000g for 30 min. at 4°C. This

second supernatant was fractionated with solid ammonium sulfate and the

fraction sedirnenting between 40% and 60% saturation was collected by

centrifugation at 60009 for 30 min at 4 OC. The precipitate from the ammonium

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sulfate step was dissolved in 20 ml of Tris-HCI buffer (pH 7.8) and dialyzed

overnight against three changes of 6L of the same buffer. The dialysate was

mixed with three times its volume of cold acetone (-20'~) and kept at -20°C for

3h. The precipitate formed was collected by centrifugation at 60009 at 4OC for 30

min. The material from the acetone step was redissolved in 10 ml Tris-HCI buffer

(pH 7.8) and pumped into a SBTI-Sepharose 4B affinity chromatography column

according to the method of Katoh et al., (1978). The column was thoroughly

washed with elution buffer to remove the unbound material after which the bound

material was eluted with 5 mM HCI at a rate of 15 mlfhr and fractions of 4.8

mlltube collected.

3.3.2 ENZYME ASSAY

The amidase activity of the trypsin fraction, was estimated using the

method of Erlanger et al., (1 961 ).

A 200 pl aliquot of an appropriately diluted isolate was added to 2.8 ml of

1 mM N a-benzoyl-DL-arginine p-nitroanilide (BAPNA) in Tris-HCI (pH 8.2)

containing 0.02M CaCI2 and the release of p-nitroanliline was measured at 410

nm at 25 OC, using Hitachi U 2000 spectrophotometer.

One BAPNA unit was defined as AA,,,,m,mi,,, x 3 x 1000 1 8800 where 8800

is the extinction coefficient of p-nitroaniline. The stock enzyme used in the study

was prepared in 5 mM HCI (pH 2.5).

1 mM BAPA was prepared as follows: 0.04359 of BAPNA was dissolved

in 1 ml dimethyl sulfoxide (DMSO). The resulting solution was made up to 100 ml

with Tris-HCI buffer, pH 8.2, containing 0.02M CaCI2.

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The protein content was determined by the modified method of Lowry et

al., (1 951) as reported by Stoscheck (1 990).

To 400 pl of sample, 400 pl of Lowry concentrate was added and incubated at

room temperature for about 12 min. 200~1 of 0.2 N Folin reagent was then added

and then vortexed immediately. The resulting mixture was incubated ai

approximately 24°C for another 30 min. The absorbance of the solution was read

at 750 nm. A calibration curve was perforrned using appropriately diluted solution

of bovine serum albumin stock solution of 2 mglml.

Lowry concentrate: This was prepared as follows:

20g of Na2C03 were dissolved in 260 ml water; 0.4 g of CuS04.5H20

was dissolved in 20 ml water; and 0.2g sodium potassium tatrate was also

dissolved in 20 ml water and mixed to form the copper reagent.

l og of sodium dodecyl sulfate (SDS) were dissolved in 100 ml of water to

give a 1 % solution

49 of NaOH were dissolved in 100 ml of water to give a 1 M solution

3 parts of copper reagent, 1 part NaOH and 1 part SDS were mixed just

before use

3.5 SDS POLYACRYLAMIDE GEL ELECTROPHORESIS

SDS polyacrylamide gel electrophoresis was carried out according to the

method of Laemmli, (1970).

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3.5.1 CASTING OF GELS

The casting apparatus were assembled. A 12% solution of the monomer

was prepared by combining al1 the reagents in Table 3.1 except the ammonium

persulfate (APS) and TEMED. The monomer solution was deaerated under

vacuum for 15 min. The deaerated monomer solution was gently rnixed with APS

and TEMED. The rnonomer solution was poured between the plates and

immediately overlayed with water. The gel was allowed to polymerize for 45 min.

The stacking rnonomer solution was prepared by combining al1 the reagents in

Table 3.2, except the APS and TEMED and deaerated under vacuum for 15 min.

The top of the resolving gel was thoroughly rinsed with water and dried with filter

paper. A well-forming comb was placed in between the plates and tilted at a

slight angle to provide for bubbles to escape. APS and TEMED were added to

the degassed stacking monomer solution and poured on top of the resolving gel.

9 The comb was aligned in its proper position, and polymerization allowed to

proceed for 45 min.

3.5.2 SAMPLE PREPARATION AND SDS POLYACRYLAMIDE GEL ELECTROPHORESIS

The samples were diluted with at least 4 vol. of complete SDS-reducing

buffer and heated at 950C for 4 min. in boiling water bath and used for the

electrophoresis. The electrophoresis cell was assembled, and the lower and the

upper reservoirs filled with electrode buffer as per Table 3.3 and the comb was

removed from the stacking gel. The prepared samples were loaded into the wells

in the stacking gel by layering them under electrode buffer using a microliter

syringe. The leads were then attached to the power supply (BioRad 3000 Xi) and

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Table 3.1 Formulations of SDS PAGE Resolving Gel

Component Resolving gel (1 2%)

Water 3.35 ml

1.5M Tris-HCI, pH 8.8 2.5 ml

10% SDS 0.1 ml

Acrylamidelbis 4.0 ml

10% ammonium persulfated 50 pI

TEMED 5 PI

d Prepared freshly each day

Table 3.2 Formulations of SDS-PAGE stacking Gel

Component Volume

Water 6.1 ml

0.5 M Tris HC1, pH 6.8 2.5 ml

Acrylamidelbis (30% T) 1.3 ml

10% SDS 0.1 ml

10% APS 50 pl

TEMED I O pl

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Table 3.3 : Solutions for running electrophoresis and staining Gels

Solution Composition

- --

%ample buffer distilled water (4ml, Tris-HCI, pH 6.8 (1 ml), 10% SDS

(1.6 ml) 2-rnercaptoethanol (0,4 ml). 0.05% (wlv)

bromophenol blue (0.2 ml)

7 Electrode buffer

1 Fixating Solution

2Staining Solution

tris(l5g), glycine (72 g) SDS (5 g) in 1 L aqueous

solution pH 8.3

trichloroacetic acid (12.5g) in 100 ml deionized water

Coornassie brilliant blue R 250, (0.1 % wlv) in 25%

propanol, 10% acetic acid and deionized water

*Destainhg Solution acetic acid: propano1:water (ratio 1 :2:7)

l Laemmli, (1970)

2 Simpson et al., (1 987)

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the electrophoresis allowed to proceed under constant voltage. The run was a stopped when the blue tracking dye was about 1 cm frorn the bottom of the glass

plates. The gels were removed from the glass plates and fixed in 12% TCA, table

3.3, solution overnight in a glass casserole container. After fixation, the gels were

soaked in an excess of staining solution, (Table 3.3), overnight, and then

destained with several changes of the destaining solution, (Table 3.3), until the

background stain was satisfactorily removed.

3.5.3 MOLECULAR WEIGHT DETERMINATIONS

The molecular weights of the trypsin fraction were determined by

cornparison of their mobilities with those of standard marker proteins of known

molecular weight which were run simultaneously on the same gel as the trypsin

O fraction. The molecular weight markers (Seeblue prestained markers from

Novex) used were myosin (250,000), bovine serum alburnin (98,000), glutamic

dehydrogenase (64,000), alcohol dehydrogenase (50,000), carbonic anhydrase

(36,000), myoglogin (30,000), lysozyme (16,000), aprotinin (6,000) and insulin P-

chah (4,000). The distance of migration of each protein was divided by the

distance traveled by the tracking dye. The norrnalized migration distances so

obtained are called the relative mobilities of the proteins (relative to the dye front)

and conventionally denoted as Rf.

The logarithms of the molecular weights were plotted as functions of the Rf

values. The unknown molecular weights were determined by linear regression

analysis.

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3.6 ISOELECTRIC FOCUSING

lsoelectric focusing to determine the isoelectric point (pl) of the trypsin

fraction was carried out using the Rotofor ce11 (Biorad). The Rotofor cell is a

modification of an apparatus originally designed by Egen et al., (1984)

Prior to the run, the anion and cation exchange membrane of the rotofor

were equilibrated overnight in 0.1 M NaOH and 0.1 M H3PO4 respectively.

A gasket was placed over the aligning pins and seated on a flat surface of the

inner assembly. The anion exchange membrane was then placed on the gasket

by the aligning notches in the membrane and the "sandwich" with a second

gasket on top of the membrane. The pins and sockets in the two halves of the

assembly were aligned and fastened together with the captive threaded sleeve

to form the cathode assembly. The process was repeated using the cation

a exchange membrane to form the anode electrode assernbly. The electrode

chambers were filled with the electrolytes immediately after assembly. The

anode was filled with about 25 ml of 0.1 M H3PO4 and the cathode was filled

with 25 ml of 0.1 M NaOH.

The assembled anode electrode chamber was slided over the ceramic

cooling finger so that the two protruding screw heads fitted into the holes in the

black plastic base of the cooling finger support. A membrane core was then

slided ont0 the cerarnic cooling finger, in such a way that the core was abutting

the acrylic ridge on the anode chamber. The focusing chamber was then slided

over the membrane core and the metal pins were inserted into the small hole in

the anode. The black nylon retaining screws were then tightened. The

assembled cathode electrode was then slided over the cooling finger, aligning

e the rnetal pins and the hole in the cathode chamber, and the nylon retaining

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a screws tightened. The assembled focusing chamber was then mounted in the

stand.

The sample was prepared by diluting 5 ml of the trypsin extract with 3 M

urea to 55 ml and 2% Bio-lyte ampholyte pH 3-10.

With the cell mounted, the cell was rotated so that the 20 collection ports

faced up. The ports were covered with some sealing tape and reinforced with an

acrylic cell-cover block and the screws lightly tightened.

The cell was then rotated so that the filling ports faced up. The cell was

filled with sample through the filling ports using a syringe. The filling ports were

then sealed with a second cell cover block.

The cooling finger was then connected to a recirculating coolant source

maintained at 40C. The high voltage leads were attached to the power supply

(Biorad 3000Xi) and the conditions for the run set as follows: voltage limit of

a 2000 V, current limit if 35 mA and power limit of 12 W.

The harvest box was loaded with twenty 12 X 75 mm culture tubes and

the lid of the box was placed in position such that each stainless steel was inside

a collecting test-tube and a vacuum source was then connected to the port on

the box. When focusing was completed, the black toggle switch was moved to

the harvest position, the power supply disconnected, the lid removed and the

Rotofor cell rnoved close to the harvest box. The cell cover blocks of the upper

and lower focusing cell chamber were then removed. Vacuum was applied to the

collection box. The needle array was mounted on the two alignment pins on the

bottom of the chamber. The needle array was grasped with fingers of both hands

while placing the thumbs on the top of the focusing chamber. The needles were

then pushed uniformly al1 the way through sealing tape into the chamber. The 20

fractions were then simultaneously aspirated from the cell and delivered to the

collection tubes. The run was completed within 4-6 h

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a 3.6.2 FRACTION SCREENING

(1) The pH range of the collected fractions were read using a standard pH

meter (Corning, 220).

(2) The amidase activity of the fractions were assayed for using the

method of Erlanger et al., (1 961) on a Hitachi U 2000 spectrophotometer.

The fractions exhibiting amidase activity were pooled together, diluted to

55 ml using deionized water and refractionated.

3.7 AMINO AClD COMPOSITION ANALYSE

The trypsin fraction for amino acid analysis was freeze-dried using a

Labanco freeze drier. The dried samples were then transfered into culture tubes

(6 x 50 mm) which were previously muffled at 450°C overnight. The tubes were

then placed in a Waters reaction via1 and dried in a Waters Pico-Tag Work

Station (Waters, CT, USA). 200pl of 6N HCI containing 1 % phenol was added to

the vial. The via1 was alternately purged (3 times) with dried nitrogen then heated

at 150°C for I h under vacuum. The samples were cooled and again evacuated

to remove traces of hydrochloric acid. The hydrolysates were applied to a

Beckman System 6300 High Performance Analyzer using the method of

Vereeragan and Gibbs (1989), Table 3.4. A strong cation exchange was used

with a temperature gradient from 50 to 65°C at I0Clmin. The amino acids were

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Table 3.4 Program for amino acid analysis on Beckman HPLC System 6300

Sodium hydroxide

Buffer Molarity Flow rate pH Time Temperature

(mllh) (min) (Oc)

Sodium citrate 0.2 20 3.0 52.0 50

0.4 20 5.1 17.2 65

0.7 20 6.2 27.4 77

51 .O 50

36.0 65

2. O 77

Ninhydrin reagent 53.0

End of data collection 50.0

Sample loop filled 61 .O

Sample to be injected 63.0

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a separated using sodium citrate buffer, in a period of 50 min.

3.8 INHIBITION STUDIES

The sensitivity of the cunner trypsin to various inhibitors was investigated

according to the method of Simpson and Haard, (1984),

Soybean trypsin inhibitor (SBTI) was dissolved in deionized water to the

following concentrations: 0.006, 0.001, and 0.1 mglml. The trypsin solution was

added separately to equal volumes of the SBTl solution and incubated on ice for

30 min and the residual trypsin activity assayed using BAPNA (pH 7.8) as

substrate

Aprotinin was diluted with deionized water to the following concentration,

e in trypsin inhibitor units (TIU): 0.02, 0.03, 0.04 and 0.06 TIUIrnl. Trypsin solution

was mixed with an equal volume of aprotinin, incubated on ice for 30 min and the

residual activity determined by assay with BAPNA (pH 7.8) as substrate.

Different substrate concentration in the range of 1-5 mM were used for

aprotinin while 1-7 mM range were used for SBTl in the determination of the

kinetic parameters of Km, (substrate affinity), V,,,, (maximum velocity) and Ki

(inhibitor dissociation constant). Km and V,,, were determined using the

Lineweaver-Burk equation :

Ki was deterrnined using the 1, method, where

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where 15, is the concentration of inhibitor required for 50 % inhibition of the

enzyme activity.

3.8 PECTIN METHYLESTERASE ACTlVlTY DETERMINATION

PME activity was monitored by the spectrophotometric rnethod of

Hagerman and Austin (1986)

The method is based on the color change of a pH indicator dye during the

PME-catalyzed reaction. As ester bonds are hydrolyzed, acid groups are

produced to lower the pH, which causes a color change in the indicator dye. The

a color change is continuously monitored spectrophotometricaIly to obtain the

initial rate of the reaction.

For the assay itself, PME was dissolved in deionized water whose pH has been

pre-adjusted to 7.5 with 2N NaOH. In a cuvette, 2 ml of 0.5 % solution were

mixed with 0.15 ml of 0.01 % bromothymol blue in 0.003 M potassium phoshpate

buffer pH 7.5 and 0.83 ml water, and the initial absorbance measured at 620 nm

using a Hitachi U 2000 spectrophotometer. Twenty (20) pl of 20pg solution of

PME was added to the mixture and the rate of decrease in absorbance A620 (A

A ) was recorded. 6201rnin.

The method was calibrated with appropriate dilutions of a 0.87 mM galacturonic

acid. To achieve constant starting pH for the reaction, al1 solutions (water, pectin

and dye) were adjusted to pH 7.5 with 2N NaOH just before each trial was

started.

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3.8.1 EFFECT OF CUNNER TRYPSIN ON PME ACTIVITY

Trypsin concentrations of 10, 20 and 40 uglml were incubated with equal

amounts of PME in solution (20 uglml). The mixture was incubated on ice for 4 h.

Portions of the mixture were taken at 1 h interval and the residual PME activity

assayed using the method of Hagerman and Austin (1986). The trypsin-treated

PME were stored on ice for 21 days to test for reactivation of the PME activity.

3.8.2 EFFECTS OF CUNNER TRYPSINS ON HEAT-TREATED PME

Twenty (20) uglml portions PME were incubated at 40 and 45°C for 30

min., and immediately cooled on ice. Equal volumes of cunner and bovine trypsin

were added to the heat-treated PME, incubated on ice for 4h. Sample aliquots

were taken every l h and the residual enzyme activity assayed using the method

of Hagerman and Austin (1986).

3.9 PPO ACTlVlTY DETERMINATION

PPO activity was determined according to the method of Savagon and

Sreenivasan (1978). A 0.2 ml portion of mushroom PPO solution in sodium

phosphate buffer, pH 6.5, was added to 2.8 ml of 5 mM DOPA in 0.05 M sodium

phosphate buffer pH 6.5, and the formation of dopachrome was measured at

475 nm at 25°C in a Hitachi U 2000 spectrophotometer

One unit of activity was defined as AA4,,,,m,, 10.6

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3.9.1 EFFECT OF CUNNER TRYPSIN ON PPO ACTlVlN

Equal volumes of appropriately diluted trypsin fraction were incubated with

equal volumes of PPO in solution. The mixture was incubated on ice for 4 h.

Portions of 0.2 ml were taken at 1 h interval and the residual PPO activity was

assayed by measuring the formation of dopachrome at 475 nrn at 25"C, on a

Hitachi U 2000 spectrophotometer. The trypsin treated PPO was stored on ice

for 21 days to test for reactivation of the enzyme activity.

3.9.2 EFFECT OF CUNNER TRYPSIN ON HEAT-TREATED PPO ACTlVlTY

O Portions of PPO were incubated at 50°C and 55°C for 30 min., and

immediately cooled on ice. Equal volumes of appropriately diluted cunner and

bovine trypsins were incubated with the heat-treated PPO for a period of 4h.

Sample aliquots (75 pl) were taken every 1 hr and the residual PPO activity

determined by measuring the formation of dopachrome at 475 nm at 25" on a

Hitachi U 2000 spectrophotometer.

3.10.1 OPTlMlZATlON STUDIES / EXPERIMENTAL DESIGN

The different factors and their levels used in this study were [E]/[S] ratio

(0.5 - 1.5), incubation time (1 - 4h) and temperature (15 - 35"C), where the

substrate, S, is considered to be PME or PPO. Table 3.5 shows the parameters

with their levels and the coded and uncoded variables. To study the

a simultaneous effect of these factors on the residual activities of PME and PPO

activities, a 3 x 3 factorial design (Schmidt and Launsby, 1992) was used.

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The model is indicated below:

X,, X, and X, are the variables or the factors namely enzyme:substrate ratio,

incubation time and temperature respectively and p values represent the

corresponding regression coefficients

To predetermined volumes of PME, 20 pg/ml, (20 pl) and PPO, 25 p g h l

(75 pl) the calculated [E]/[S] ratio (0.5 - 1.5) added and the resulting mixture

incubated at the predetermined temperature (15 - 35 OC) for a specified time (1 -

4 h). There were in al1 20 different combinations.

Statistical analysis and three dimensional plots were performed using the

statistical tool pack of Microsoft Excel4.0 (1994).

3.1 1.1 TREATMENT OF ORANGE JUlCE

The trypsin-treated PME and the untreated PME were added to different

portions of commercial orange juice (Tropicana). The cloud stability and the pH

of the juice were measured over a storage time of 21 days as per the procedure

m described by Owusu Yaw et al. (1988). For this, 10 ml portions of the sample

were centrifuged at 3209 for 10 min. The supernatant was filtered through

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Table 3.5 Values of coded levels in Experimental design

Process Variable Code Levels

-il O 1 -

[E]/[S] ratio XI 0.5 'l 1.5

Incubation time (h) x2 1 2.5 4

Temperature (OC) X, 15 25 35

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Whatman #41 filter paper (Whatman Limited, England). Cloud loss was

determined by measuring the absorbance at 660 nm on a Hitachi U 2000

spectrophotometer, using 3 ml cuvettes with distilled water as blank. The

experiments were run in triplicates.

3.1 1.2 pH MEASUREMENTS

This was measured using standard pH meter (Corning 220) by placing the

pH electrode in 10 ml of sample in a beaker and stirring with a magnetic stirrer.

The pH was recorded when the readings were stable.

3.1 1.3 STORAGE OF TREATED ORANGE JUICE

The treated and untreated orange juice were then stored in glass

containers at 4°C for a period of 21 days and readings of cloud stability and pH

taken fotthnightly.

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CHAPTER IV

RESULTS AND DISCUSSIONS

4.1.1 Recovery of trypsin fraction

The recovery of the trypsin fraction is summarized in Table 4.1, which

shows that the specific activity increased from 0.55 for the crude fraction to 2.02

unitlrng for the affinity fraction (trypsin fraction). The purity of the extraction was

3.7 fold with a yield of 1.4%. The protein content as determined by the enhanced

Lowry assay was about 2.3 mg/lOg, using the standard curve for the protein

determination in Figure 4.1.

4.1.2 Elution profile of the trypsin fraction on SBTI-Sepharose Affinity media

9 The elution profile of the trypsin fraction from the SBTI-affÏnity media after

the application of the acetone fraction is shown in Figure 4.2 which shows the

absorbance at 280 nm, (A2,,), and the corresponding change in absorbance per

minute (dA/min) at 410 nm. There was a gradual increase in the absorbance at

280nm, (4,) up to a maximum and then a decrease after fraction 9. A second

gradual increase was observed from fractions 13-15. The dA/min followed the

same trend as observed for the A,,. The fractions showing trypsin activity, tubes

4-8 and 13-15, were pooled together, concentrated and used in subsequent

analysis.

4.1.3 Electrophoresis of the trypsin fraction

The graph of R, versus log. molecular weights of standards used to

@ determine the molecular weights of the protein bands are shown in Figure 4.3.

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Table 4.1 : Recovery of trypsin from the pancreas of the cunner fish.

Step Total Total Total Specific Yield % Purification volume Protein activity activity fold

(ml) (mg) (units) (unitslrng)

Crude extract (300Os>

Crude extract (1 000s)

Acetone fraction

Affinity fraction

10.09 of pancreatic tissue was used.

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t 1 1 I

O 20 40 60 80 1 O0 BSA concentration (uglml)

Figure 4.1 : Calibration curve for protein content determination using the enhanced

Lowry method and bovine çerum albumin (BSA) as standard. Aliquot of stock BSA

concentration of 2 mglml were used to prepare the standard curve.

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1 3 5 7 9 11 13 15 17 19 21 2 4 6 8 10 12 14 16 18 20 22

Tube number

abs 280 nm dAlmh 1-91

Figure 4.2: Elution Profile of the acetone fraction on SBTI-Sepharose

Aninity media. Three (3) ml of acetone fraction cuntaining 1.5 mglml protein

were injded onto the wlumn.

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O 0.2 0.4 0.6 O. 8 1 Mobility (F+ )

Figure 4.3: Calibration curve for molecular weight detemination for SDS-PAGE

electrophoresis

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Figure 4.4: SDS-PAGE gel showing the migration of the proteins. Lane 1

shows the trypsin fraction from the SBTI-Sepharose affinity media and

lane 2 shows the standards, (Seeblue prestained markers from Novex)

from top to bottom: myosin, 250.000; BSA, 98,000; glutamic

dehydrogenase, 64,000, alcohol dehydrogenase, 50,000; carbonic

anhydrase, 36,000; myoglogin, 30.000; lysozyme, 16,000; aprotinin,

6,000; and insulin p-chah, 4,000.

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m The electrophoresis of the trypsin fraction on SDS-PAGE gel is shown in Figure

4.4. The electrophoregram showed a distinct band at 24,000 kDa. This was

consistent with the findings of Simpson and Haard (1 984).

4.1.4 Stability of Various Fractions at Different Storage Temperatures

The stability of an enzyme fraction is of importance to ensure that no loss

of activity occurs during the extraction process. The integrity of the three

dimensional structure of the active site is essential for maintenance of activity

(Whitaker, 1994). One of the several factors affecting the integrity of the three

dimensional structure include temperature. Generally, enzymes are stable at

lower temperatures (Schwimmer, 1981). The stability of the various fractions on

ice and -20°C are shown in Figures 4.5 a & b respectively. The trypsin fraction

had the highest specific activity followed by the acetone and then the ammonium

0 sulfate fraction for both storage temperatures. There was a significant difference

in the specific activities of the fractions kept at 0°C and -20°C (p 2 0.05) for the

ammonium sulfate fraction. On the other hand, there were no significant

differences for either the acetone or the trypsin fraction stored at both storage

temperatures. The results of the analysis of variance (ANOVA) performed on the

results are shown on Table 4.2 a - 4 . 2 ~

4.1.5 lsoelectric focusing of the trypsin fraction

The isoelectric pH (pl) of a protein is the pH at which the net charge on a

protein is zero and has no mobility in an electric field. Proteins are minimally

soluble at their pl (Cheftel et al. 1985; Whitaker, 1994). Figures 4.6 a & b show

the pH-activity profile of the trypsin fraction after isoelectric focusing. After

refractionation, the trypsin showad two peaks, the lowest peak corresponding to

the ranges 6.48-6.83 and the highest peak corresponding the ranges 9.86-1 0.25. * This is consistent with the observation that the trypsin fraction had two proteins.

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Storage time (weeks)

ammonium sulfate

Storage time (weeks)

acetone fraction

trypsin fraction

Figure 4.5: Effect of storage temperature on the stability of the

ammonium sulfate, acetone and trypsin fractions. (a) storage

on ice (b) storage at - 20 C

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Table 4.2a One-way ANOVA of the storage on ice and at -20°C for the

ammonium sulfate fraction at p 5 0.05

Parameter Mean Variance P

O O C 0.774 0.008

-20 OC O. 893 0.002 0.028

Table 4.2b One-way ANOVA of the storage on ice and at -20°C for the

acetone fraction at p I 0.05

Parameter Mean Variance P

Table 4 . 2 ~ One-way ANOVA of the storage on ice and at -20°C for the

affinity fraction at p 0.05

Parameter Mean Variance P

O O C 4.61 3 O. 074

-20 O C 4.672 0.078 0.743

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Tube number

1 2 3 4 5 6 7 8 9 10 I l 12 13 14 15 16 17 18 19 20 Tube number

Figure 4.6: (a) Fractionation and (b) refractionation of the trypsin fraction

after isoelectric focussing at 4 C on Biorad rotofor system

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a A pl value reported for bovine trypsin is around 9.3 (Kiel, 1971). A trypsin

fraction recovered from the fungus, Metarhizium anisopliae, however, has been

reported to have two proteins fractions with rather low pl values of 5.4 and 4.6,

both of which are lower than the bovine or the cunner trypsins (Cole et al. 1993),

of 9.3 or 6.48-6.83 and 9.86-1 0.25.

4.1.6 Amino acid composition analysis

The elution of amino acid standards is shown on Figure 4.7. The acidic

and straight chain hydroxy amino acids were the first to be eluted. On increasing

the temperature, other small and neutral amino acids were eluted. lncreasing the

pH and temperature further, eluted the basic amino acids. The amino acid

composition of the trypsin fraction showing the mole fraction and number of

O residues is shown in Table 4.3. The trypsin fraction was found to have 220 amino

acid residues, whilst bovine trypsin has been reported to possess 223 residues

(Kiel, 1971). The residues were very rich in several of the common amino acid

residues including Asp, Glu, Ile, Leu and Ser, except Arg, Lys, Phe, Tyr and Val.

The amino acid composition was similar to those of trypsins from other sources

such as the Greenland cod and Atlantic cod, bovine, porcine and human

(Simpson et al. 1989; Simpson and Haard, 1984; and Kiel, 1971). Fish trypsins

including the cunner have been reported to be stable at alkaline pH values

(Simpson et al. 1989). The low levels of basic amino acid residues (Arg and Lys)

makes them resistant to autodigestion, since trypsins, are active in the alkaline

pH and hydrolyze peptide bonds at the carboxyl side of arnino acid residues

contributed by Arg or Lys. Furthermore if the amino acid next to the arginine or

lysyl residue in the primary structure of trypsin polypeptide chain is a proline,

then the trypsin molecule will be resistant to autodigestion. Moreover, if the

arginine or lysine residues form the carboxyl end of the amino acid chain, the

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Figure 4.7: Chromatogram of amino acid standards at 570 nm using

norleucine as interna1 standard

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Table 4.3 Amino acid composition of the cunner trypsin

Amino acid Mole % Number of

Residuesa

Asp + Asn 9.70 21

Thr 4.82 II

Ser 10.09 18

Glu + Gln 8.40 27

G ~ Y 12.23 15

Ala 6.68 14

Val 6.32 6

Met 2.94 II

IIE 4.91 20

Leu 8.95 20

Tyr 4.2 9

Phe 1.86 4

His 4.52 10

LYS 3.66 8

T ~ P - -

Arg 2.02 4

Pro 4.99 II

CYS 3.60 14

Total # residues 220

'Based on a molecular weight of 24,400 KDa

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protein becomes less susceptible to autodigestion at alkaline pH (Segel, 1976).

4.2 The Effect of lnhibitors on the trypsin fraction

Both the cunner and the bovine trypsin were susceptible to inhibition by

SBTI. The extent of inhibition of cunner and bovine trypsin activity with

increasing substrate concentration is shown in Figures 4.8 a & b. lncreasing the

inhibitor concentration resulted in corresponding increase in the percent

inhibition of both trypsins. However, for the cunner trypsin, the effect of inhibition

was lowered as the substrate concentration, [SI, increased from 3 mM to 7 mM,

Fig 4.8a. The same trend was observed for the bovine trypsin, Fig. 4.8b, but a

higher substrate concentration of 5 mM was required before the percent

inhibition was lowered.

Both the cunner and the bovine trypsin were susceptible to inhibition by

aprotinin. The extent of inhibition of both cunner and bovine trypsin activity with

increasing [SI are shown in Figs. 4.9 a & b. lncreasing the inhibitor concentration

resulted in the corresponding increase in the percent inhibition of both trypsins.

The reverse of the observation with SBTI, however, resulted. A higher [SI was

required by the cunner trypsin, Fig. 4.9a, to relieve the inhibition. On the other

hand, increasing the [SI from 3 to 5mM resulted in a decrease in the inhibition of

the bovine trypsin by aprotinin. The extent of the inhibition relief was relatively

lower in aprotinin than in SBTI, suggesting that different types of inhibition may

be exhibited by both inhibitors.

The Lineweaver-Burk plots of SBTl inhibition of cunner and bovine trypsin

are shown in Figs 4.10 a & b. SBTI exhibited a predominantly cornpetitive type of

inhibition for cunner and bovine trypsin. The plots using aprotinin as inhibitor is

shown in Figs 4.1 1 a & b. The kinetic parameters for cunner and bovine trypsin

using SBTl and aprotinin are shown in Tables 4.4a - 4.4d. 4

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Figure 4.8: Effect of increasing BAPNA concentration on SBTl inhibition.

(a) cunner trypsin (b) bovine trypsin

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-- -

0.02 TIU 0.03 TI U 0.04 TIU 0.06 TIU -m- -8. + *

Figure 4.9: Effect of increasing BAPNA concentration on aprotinin inhibition.

(a) cunner trypsin (b) bovine trypsin

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From table 4.4a, the substrate affinity, Km, increased 5-fold after

increasing [Il from 0.025 to 0.1 0 mg/ml SBTI, and a 1 .l fold decrease in the

maximum velocity, Vma,, value. From Table 4.4b, the Km values for bovine trypsin

exhibited a 12-fold increase whilst there was only a 7.4 fold increase in VmaX

values after an increase of [Il from 0.025 to 0.10 mglml of SBTI. The results

show a predominantly cornpetitive inhibition of both cunner and bovine trypsins

by SBTI. It was also observed from the effect of SBTI on the substrate affinity

that the inhibitor binds to the enzyme in such a way as to block its active sites

(Blow et al, 1974). A low K, value denotes a high susceptibility of an enzyme to

inhibition (Segel, 1978; Whitaker, 1994). From Tables 4.4a & b, the cunner

trypsin fraction had lower K, values than the bovine trypsin and thus appears to

be more susceptible to inhibition by SBTI than bovine trypsin.

The effects of aprotinin on both cunner and bovine trypsin showed a

mixed type of inhibition, as both V,,, and Km decreased with increase in [Il. There

m was a 1.76 and 2.8-fold decrease for Vmax and a 6 and 1.3-fold decrease in the Km

for the cunner trypsin fraction and bovine trypsin respectively. In contrast to

observations of the enzyme's susceptibility to SBTI, the bovine trypsin exhibited

lower K,, values than the cunner trypsin. Thus the bovine trypsin was more

susceptible to inhibition by aprotinin than the cunner trypsin.

4.3. Dependence of Y, on Temperature

The enzyme-substrate affinity, (Km), is reported to be affected by the

habitat temperature of the organism (Haard et al., 1982), and that the Km of

trypsins from various fishes correlated with the temperature preferendum of each

species. The dependence of Km, the substrate binding affinity, of cunner trypsin

on temperature is shown in Figure 4.12. The Km increased with increase in assay

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control 0.025 mg 0.075 mg 0.1 mg - -$à- A ++ -

Figure 4.10: Lineweaver-Burk plot for the trypsins using SBTl as inhibitor.

(a) bovine trypsin and (b) cunner trypsin, with 1 mM BAPNA (pH 8.2) as

su bstrate

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control0.02 TIU 0.03 TIU 0.04 TIU 0.06 TIU I * e + * +K 91

Figure 4.11: Lineweaver-Burk plot for the trypsins using aprotinin as inhibitor.

6 (a) bovine trypsin and (b) cunner trypsin, with 1 mM BAPNA (pH 8.2) as

substrate

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Table 4.4a Kinetic data on SBTl inhibition of cunner trypsin

[il (mg) V,, (un itslmin .) Km (mM) K, (mM x10 ")

Table 4.4b Kinetic data on SBTl inhibition of bovine trypsin

Ill mg) V,,,, (unitslmin.) Km (mM) K, (mM x10

0.00 1.42 + 0.01 1 0.99 ir 0.085 0.00

0.025 1.91 1 0.060 3.41 k0.214 28.8 + 0.006

0.075 1.52 k0.002 5.20 + 0.089 4.06 t0.005

0.1 O0 2.02 & 0.001 12.47 + 0.041 4.67 t0.001

Table 4.4~ Kinetic data on aprotinin inhibition of cunner trypsin

[Il ( T u V,,, (units/min.) Km (mM) Ki (mM x10 ")

Table 4.4d Kinetic data on aprotinin inhibition of bovine trypsin

[Il (w Vm,, (un itslmin .) Km (mM) Ki (mM x i 0 -3)

0.00 1.42 I 0.01 1 0.99 a 0.085 0.00

0.02 2.08 k 0.123 0.97 ,+ 0.20 7.5 k0.0003

0.03 1.39 + 0.053 0.88 t 0.02 3.9 +0.0005

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I O 20 30 40 50

Assay temperature (C)

Figure 4.12: Dependence of cunner trypsin Km on temperature. Cunner

trypsin fraction depicts a "type 3" Km -temperature dependence

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e temperature being insensitive at lower temperatures. Greenland cod trypsin, and

trypsins from Salmo atra and Tnturus alpestris, have also been reported to

exhibit this type of response (Simpson and Haard, 1987; Hofer et ab, 1975). This

type of dependence is called the "type-3" response (Hultin, 1978). In this

response, the Km increases with temperature as the assay temperature is

increased, but at lower temperatures, insensitivity to temperature is observed.

The minimum Km observed in thiç Km-temperature profile coincides with

the habitat temperature of the cunner fish, which is around lQ°C, implying that

the cunner fish has adapted to have the highest substrate affinity at the habitat

temperature to be able to utilize the food ingested. Bovine trypsin on the other

hand has been reported to show a "type 2" Km temperature response, in which

the Km remains constant, neither increasing or decreasing with temperature

(Hultin, 1978; Simpson and Haard, 1987).

4.4 Effects of trypsins on Native PME and PPO

PME is known to cause the breakdown of juice cloud in citrus juices

(Chaplin and Bucke, 1990) and PPO is known to cause the enzymatic browning

observed in fruits, vegetables and crustacean species (Chen et al., 1993; Zhou

and Feng, 1991; Valero et al., 1988). Trypsins from the stomachless cunner

have been reported to hydrolyze native proteins better than trypsins from the

species with a physiologically and morphologically distinct stomach as in the

bovine (Simpson and Haard, 1987b). However, there are wide differences

among proteins in their susceptibility to proteolysis (Whitaker, 1994).

The effects of differing concentrations of cunner and bovine trypsin on

PME at differing pectin concentrations on PME activities are shown in Figures

4.14, 4.15 and 4.16. The hydrolysis of PME was measured as a loss of

enzymatic catalysis. The cunner trypsin treatment resulted in a loss of 75 % of

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the initial activity of PME after 4h incubation at 4°C using 0.5 % pectin solution.

Treatment of PME with bovine trypsin on the other hand resulted in only a loss of

35 % of the initial activity. Lowering the pectin concentration to 0.35 %

decreased the difference observed to 60 and 50 % loss initial activity for the

cunner and bovine trypsins, respectively. Increasing the [enzyme]/substrate ratio

to 1 and 2, at a pectin concentration of 0.35 %, the bovine trypsin tended to

decrease the percent initial activity better than the cunner trypsin. This

observation is consistent with the report of Castaldo et al. (1991), of the effects

of proteolytic enzymes on PME activity. PME from orange has also been

reported to have 22 Arg and Lys residues (Castaldo et al., 1991) for the trypsins

to hydrolyze.

The effect of the trypsins on native PPO activity is shown in Figure 4.77.

Trypsin frorn cunner hydrolyzed native PPO better than bovine trypsin, resulting

in loss of 75 % and 55 % of initial activity upon incubation for 4h with cunrier and

bovine trypsins respectively. Generally proteolytic enzymes are known to

8 hydrolyze peptide bond when that portion of the protein molecule is in the

denatured state (Whitaker, 1994), and even if they do hydrolyze native bonds,

the rate of hydrolysis is very low. However, the observations with the cunner

trypsins show that the cunner trypsin hydrolyzes native proteins (PME and PPO)

better than the bovine trypsin. This observation is consistent with the results

observed with a trypsin-like enzyme from the stornachless crayfish (Pfleiderer et

al, 1967), trypsins from the stomachless cunner on ribonucease and hemoglobin

(Simpson and Haard, 1987b) and of trypsins from the stomachless crawfish on

PME activity (Jeong et al. 1994). This is an adaptation of the species without a

distinct stomach, to counterbalance the absence of the acid denaturation of

proteins that occur in the stomach which makes the proteins amenable for

digestion by the alkaline proteases in the small intestines.

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-0.14 ' I I l I 1 I l

O. 1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Galacturonic acid concentration (umol)

Figure 4.13: Calibration curve for PME assay. Aliquots of stock galacturonic acid

solution (0.87 mM) were used to generate the standard curve, with 0.5 % pectin

solution at 25 C

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O 1 2 3 4

Tirne (hr)

i 8 i i 1

4

Time (hr)

-*-. cunner trypsin -O- bovine trypsin

Figure 4.14: Effect of cunner and bovine trypsins on PME activity using

an enzyme concentration of 0.5 and (a) 0.35% and (b) 0.5% pectin solutions

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O 1 2 3 4 Time (hr)

8 I 1 1 I

1 2 3 4

Time (hr)

-.m-- cunner trypsin -a- bovine trypsin

Figure 4.1 5: Effect of cunner and bovine trypsins on PME activity uskg

an enzyme concentration of i and (a) 0.35% and (b) 0.5% pectin solutions

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Time (hr)

1 2 3 4

Tme (hr)

-- cunner trypsin -+ bovine trypsin

Figure 4.16: Effect of cunner and bovine trypsins on PME activity rising

an enzyme concentration of 2 and (a) 0.35% and (b) 0.5% pectin solutions

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4.5 Effects of trypsins on heat-denatured PME and PPO

The effects of cunner and bovine trypsins on heat-denatured PME at 50

and 55°C are represented in Figures 4.18 a-c. Heat treating PME at 50 and 55°C

for 3' min., resulted in 20% and 70 % loss of the initial activity respectively.

Treatrnent of the heat-denatured PME at 50°C with cunner and bovine trypsins

resulted in a loss of 90% and 60% respectively of the remaining PME activity.

Conversely, treatment at 55°C of PME resulted in a loss of 30% and 45% PME

activity with cunner and bovine trypsin respectively. Thus heat denaturation at a

higher temperature (55°C) resulted in a higher degree of hydrolysis of PME with

bovine trypsin than the cunner trypsin.

Effects of trypsins on heat-treated PPO at 40 and 50°C are shown in

Figures 4.19 a-c. Heat treatment of PPO at 40 and 50°C resulted in a loss of

about 10% and 80% of the initial PPO activity respectively. Treatment of PPO

e denatured at 40°C, resulted in a loss of 25% and 40% of the PPO activity with

bovine and cunner trypsin respectively. On the other hand, 50°C treated PPO

resulted in a loss of 95% and 98.5% of the initial PPO activity with cunner and

bovine trypsins respectively. This observation was similar to the effects of the

trypsins on PME activity.

In solution, proteins (e.g., PPO and PME) are known to exists in at least

three forms narnely the native, reversibly denatured and irreversibly denatured

forms. Of the three forms, the reversibly denatured forrn is subject to extensive

proteolysis. The other two forms are somewhat susceptible to proteolysis, but the

contribution of these two forms to the entire proteolysis is very low or negligible

(Whitaker, 1994). Increaising the temperature of incubation of PME or PPO,

therefore, increases the denatured forms rather than the native form, thus

increasing the level of hydrolysis of the heat-denatured proteins over the native

proteins. Trypsins are known to hydrolyze peptide bonds at the carboxyl ends

a contributed by arginine or lysine residues (Yamamoto, 1975). The extent of

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Incubation l ime (hr)

B--

bovine trypsin

O-

cunner tvpsin

Figure 4.17: Efiect of cunner and bovine trypsins on native PPO activity

using 5 mM DOPA as substrate at 25 C

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Temperature (C)

O 1 2 3 4

incribation time (h)

incubalion tirne( h)

- D. -e- bovine trypsin cunner trypsin

Figure 4.18: (a) Effect of heat treatment on PME activity and the effect of cunner

and bovine trypsins on heat-denatured PME at (b) 50 C and (b) 55 C

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O L

1 O 20 30 40 50 Tcmperature (C)

Incubation Time (h)

m- -@- bovine trypsin cunner trypsin

Figure 4.19: (a) Effect of heat treatinent on PPO activity and the effect of cunner

and bovine trypsins on heat-denatured PME at (b) 40 C and (b) 50 C

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hydrolysis of a protein such as PME and PPO will also depend primarily on the

amount of lysine and arginine residues present. The type of amino acid residue

next to the arginine or lysine residue in the polypeptide chain such as proline will

also make a protein more resistant to trypsin attack (Kiel, 1971). Moreover, the

degree of hydrolysis can be affected if the lysine or arginine residues form the

carboxyl end of the proteins (Segel, 1976).

4.6: Reactivation studies of trypsin-treated PME and PPO.

Enzyme reactivation is of great importance in the food industry since this

can result in spoilage of the particular food during storage (Schwimmer, 1987).

The effects of storage time on the reactivation of trypsin-treated PME and PPO

are shown in Figures 4.20 and 4.21 respectively. The control PME solution

@ retained al1 its activity throughout the 21 day storage, indicating that the enzyme

is very stable at 4°C. There was no reactivation of the trypsin treated PME or

PPO during storage. Increasing the cunner trypsin concentration (Figure 4.20a)

from 0.5 to 2, it was observed that PME activity was reduced to zero at day

21,12 and 3. On the other hand, for bovine trypsin, (Figure 4.20b) the days were

21, 18 and 9 suggesting that the inactivation of PME by the trypsins was

irreversible. PME treated with supercritical carbon dioxide has been reported to

show sorne reactivation after 15 days of storage at 4.4"C (Balaban et al., 1991 ),

indicating that the treatment was reversible. The observation with the cunner

trypsin therefore, makes it more desirable as an alternate way for PME

inactivation.

Figure 4.21 shows the reactivation studies of PPO during storage at 4°C.

PPO did not show any reactivation, but PPO retained a substantial amount of its

initial activity, up to 20 % and 45 % for cunner and bovine trypsin treatrnent

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O 3 6 9 P 2 15 18 21 Days

control 0.5 A.0 2.0 -wt -*+

Figure 4.20: Reactivation studies of trypsin treated PME with (a) cunner

and (b) bovine. The substrate was 0.5 % pectin solution. The storage

studies were carried out at 4 C

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control cunner bovine r-i- +

Figure 4.21: Reactivation studies of trypsin treated PPO at 4 C using 5 mM

DOPA (pH 6.5) as substrate.

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respectively for the 21 day storage. The residual activity so observed turned the @ substrate DOPA brown, indicating that the residual activity was enough to cause

some undesirable discolorations in foods. In this respect, PPO showed some

resistance to proteolysis during storage, and this may be due to some of the

factors discussed in section 4.3 above. Also, Robinson and Dry (1992) reported

that a PPO fraction from the broad bean leaf retained its activity even after

proteolysis to remove a 15-18 kDa peptide. This suggests that the active sites of

these PPO molecules had not been fully destroyed by the proteolysis.

Furthermore, in some proteins, after initial hydrolysis of some of the bonds, the

remainder of the molecule becomes less susceptible to hydrolysis (Whitaker,

1994; Schwimmer, 1981). This changes in susceptibility may be due to changes

in the conformation of the protein after the initial hydrolysis resulting in a less

susceptible protein to enzyme hydrolysis.

a 4.7 Cornbined effect of [E]/[S] ratio, incubation time and temperature on

PME and PPO.

Analysis of variance for the response of % PME inactivation, using the

model in section 3.10.1 was significant (pc0.05) and had f values of 0.92 and

0.95 for cunner and bovine trypsin respectively. For % PPO inactivation iL values

of 0.91 and 0.94 were obtained for cunner and bovine trypsin treatrnents

respectively. The parameter estimates for % inactivation of PME and PPO for

both cunner and bovine trypsins are shown in Table 4.5. The parameters that

were insignificant were dropped from the model, and the data re-analyzed. The

mathematical model for PME inactivation and the response surface plots were

then generated from the reanalyzed parameter estimates.

The equations used in the generation of the three dimensional response

surface plots are as follows:

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Table 4.5 Parameter Estimates for percent PME and PPO inactivation

% PME inactivation % PPO inactivation

Parameter Cunner trypsin Bovine trypsin Cunner trypsin Bovine trypsin

l ntercept 99.24" 99.52" 57.57" 78.40"

X1 14.1 8" 10.67" -1 0.48" -5.99"

X2 3.1 6"' 2-78"' -0.48"' -1.65"'

X3 32-63" 18.69" -3.74"= -4.5gnS

XI2 -7 0.58b -1 1 .6Ia 1.72"' -4.8gb

x: -22.22" -1 9.02" -9 -25" -9.64"

x t -1 1.71 -7.00~ -6. 34" -1 5.97a

X1X2 -6.36"" -5.18"" -3.3Sns -3.1 5""

XI% -5. 72"$ 3.98"" -4.98"" -2.34"'

'2'3 4.33ns 3.98"' -8.33" -4.77""

" Significant at 5 % level; Significant at 10 % level; "" Not significant; X, =[E]I[S]

ratio; X, = incubation time (h); X, = Temperature (OC)

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Cunner trypsin

% inactivation PME, Y, = 90.58 + 14.18X, + 32.63X3 - 21.16Xt-10.56~: (1)

% PPO inactivation, Y, = 58.98 - 10.48 XI - 9.42 X l - 6.51 X t - 8.33X2X, (2)

Bovine trypsin

% inactivation PME, Yb= 99.52 + 10.67X, + 78.69X3 - 11 .60XlZ- 19.02X; -

2.03 X,' (3)

% PPO inactivation, Yb, = 78.46 - 5.99 X, + 4.89 X,' - 9.64 X l - 15.97 XJ? (4)

From the results of sections 4.3 and 4.5 a response of importance is that

between 80-100% inactivation of these enzymes, since these ranges resulted in

e no reactivation during storage.

Using cunner trypsin for PME hydrolysis, the response surface plots,

(Figure 4.22a), showed an increase in % PME inactivation on increasing both the

[E]/[S] ratio and temperature at a constant time, giving a linear response. Figure

4.22b depicted an increase in the % PME inactivation with both an increase in

[E]/[S] ratio and incubation time at a constant temperature, and that gave a

pronounced quadratic response. Similarly, at a constant [E]/[S] ratio, there was

an increase in % PME inactivation with increasing the temperature and

incubation time, and that also gave a quadratic response (Figure 4.22~). Using

bovine trypsin for PME hydroiysis, at a constant incubation time, increasing the

[E]I[S] ratio and temperature increased the % PME inactivation (Figure 4.23a). At

a constant temperature while varying [E]/[S] ratio and incubation tirne (Figures

4.23 b), gave a pronounced quadratic response. A similar response was

observed at a constant [E]I[S] ratio and varying the incubation time and

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0 temperature for bovine trypsin treatment (Figure 4.23~). According to Ashie

(1996), such an absence of either a unique maximum or a minimum for one of

the factors with a variation in the other factors, indicates that there is a critical or

narrow range of values for one of the factors. Thus to generate a maximum level

of PME inactivation, there exist a broad range of conditions given by such a

response. This type of response is advantageous in the food industry because

there exist, a broad range of selection by the food processor to achieve the

same results, and as such minimum levels of expensive ingredients or additives

can be selected. Example of such a response is seen in figure 4.22~. To obtain

an 80-100 % inactivation of PME at a constant ternperature of 25"C, an [E]I[S]

ratio of 0.8 for an incubation of 2.5 h or [E]I[S] ratio of 1.1 for the same

incubation time can be utilized.

This type of quadratic response may be due to a number of factors

causing either the activation or the inactivation of the trypsins. Cunner and

bovine trypsins are known to have temperature optima around 45°C (Simpson et

9 al. 1989), and PME is also known to have a temperature optimum at 45°C

(Seymour et al. 1991). The temperatures used were below the optima, thereby

decreasing the possibility of inactivation after the optima had been reached. Also

these combined treatments resulted in about 100% inactivation of PME, which

was hitherto impossible to achieve by other methods (pressure and heat

inactivation) used previously (Takahashi et al., 1993; Ogawa et al., 1990; Wicker

and Temelli, 1988), due to thermostable form of PME which was resistant to the

heat treatments. The heat treatments also affected the aroma and quality since it

led to the loss of heat labile aroma compounds of the finished product.

Furthermore, some treatments with supercritical carbon dioxide has been

reported to reactivate the PME during storage (Balaban et al., 1991). The

varying combination of treatments of temperature, time and [E]/[S] ratio provide a

wide selection of treatments as alternate treatments for cloud stabilization in

products like the citrus juices. The low ternperature used is also desirable since it

will have no effect on the arorna and quality of the juice.

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a Contrary to our expectations, using both bovine and cunner trypsins for

PPO hydrolysis, at constant temperature, increasing the [E]I[S] ratio with variable

incubation time, resulted in an initial decrease in % inactivation of PPO and then

an increase in the PPO activity (Figure 4.24 a & 4.25 a). For cunner trypsin

fraction, at a constant tirne increasing the [E]/[S] ratio and temperature resulted

in an increase in % PPO inactivation (Figure 4.24 b). Bovine trypsin treatment

resulted in an initial decrease in % PPO inactivation to a minimum and then an

increase (Figure 4.25b) just as was o b s e ~ e d for the cunner trypsin. At a

constant [E]/[S] ratio with increasing time and temperatures both cunner and

bovine trypsins, exhibited a pronounced quadratic response (Figure 4.24 c 81

4.25 c). These observations presupposes that both trypsins had an activation

effect on the PPO at certain combination levels. The temperature optimum of

PPO range from 35°C - 45°C (Valero et a/., 1988; Simpson et ai., 1987). The

temperature of operation coincided with the temperature optima of PPO, and

thus instead of inhibitory effects, there was an activation of the PPO. It was

e impossible to obtain 90-100% inactivation with any treatment. These resufts

showed that this mode1 would not be good in inhibiting the enzymic browning

observed in several food products and as such an alternate and more effective

model should be sought.

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t O0

4 0

h 6 O

4 0 yr

2 0

O

Figure 4.22 Three dimensional response surface plots showing the effects of

[cunner trypsin]l[S] ratio, incubation time and temperature, on PME

activity. (a) Effect of temperature and [E]I[S] ratio et constant time (2.5h)

(b) effect of [E]l[S] ratio and time at constant temperature (25 OC) and

(c) effect of tirne and temperature at a constant [E]I[S] ratio (1).

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T h e ( h )

1 O0

8 0

6 0 4 0

ua 2 0

O T a m p ( C )

T lm a ( h )

Figure 4.23 Three dimensional responsa surface plots showing the effects of

[bovine trypsin]/[S] ratio, incubation time and temperature, on PME

activity. (a) Effect of temperature and [E]l[S] ratio at constant time (2.5h)

(b) effect of [E]/[S] ratio and time at constant temperature (25'C) and (c)

effect of time and temperature at a constant [E]/[S] ratio (1).

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10 T lm e ( h )

O O d -

Figure 4.24 Three dimensional response surface plots showing the effects of

[cunner trypsin]/[S] ratio, incubation time and temperature, on PPO

activity. (a) Effect of [E]I[S] ratio concentration and time at constant

temperature (25 O C ) and (c) effect of time and temperature at a constant

[E]/[S] ratio (1).

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Figure 4.25 Three dimensional response surface plots showing the effects of

[bovine trypsin]/[S] ratio. incubation time and temperature, on PPO activity.

(a) effect of temperature and [E]/[S] ratio at constant tirne (2.5h) (b) effect of

[E]/[S] ratio and tirne at constant temperature (25 'C) and (c) effect of time

and temperature at a constant [E]I[S] ratio (1).

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4.8 Model Validation

The effect of some of the optimum factors were used to treat orange juice.

The effectiveness of PME hydrolysis was measured as the change in pH and the

loss in cloud in the orange juice during storage at 4°C. Cloudiness is an

important attribute in orange juice, and the cloud suspended contains most of the

characteristic orange flavor and color (Balaban et al., 1991; Castaldo et al.,

1991). The changes in the pH values so measured ranged from 3.96 to 3.85 for

the control, and 3.96 and 4.0 for al1 the other treatments. The changes in cloud

stability of the juice are shown in Figures 4.26 a & b. The control was treated

with 0.f4 units/ml PME, and there was an initial decrease of about 15% of the

cloud after day 1. This value then stayed the same until day 9, after which the

cloud deteriorated for the remainder of the study, with a loss of up to 30% of the

cloud. For the treatment of the juice with bovine trypsin at 35°C (Figure 4.25 a),

the cloud was stable up to day 7, after which there was a cloud loss of up to 30

a % of the initial cloud. Treatment of the juice with cunner trypsin at 35"C, however,

resulted in an initial loss of about I O % in the cloud. The cloud was stable over

the storage period up to day 13, after which there was an increase in the cloud

up to the end of the storage period.

At lower temperature treatments (15"C), there was cloud loss for both

cunner and bovine trypsin throughout the storage period, with a loss of 20% and

35% of the cloud using cunner and bovine respectively. The juice treated with

the cunner trypsin appeared to hold the integrity of the cloud better than the

bovine trypsin treated juice. Owusu-Yaw et al. (1988), reported a similar

observation when they used a combination of low pH and low temperature

treated orange juice over a storage period of 12 weeks. The control resulted in

more cloud loss than the juice whose pH has been lowered to 2.2. However, the

juice treated this way has been reported to have unacceptable sensory quality

(Arreola et al., 1991), and also caused a loss of up to 99% of vitamin Cl ascorbic

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O 1 2 4 7 9 11 ?3 15 18 21 Days of storage

I I I I l i 1 1 I l l

O 1 2 4 7 9 1 13 15 18 21 Days of storage

Figure 4.26: (a) An [E]I[S] ratio of 0.3 and 1.5 bovine and cunner at 35 C

for 1.3 and 0.4 h respectlvely ard (b) [E]l[S] ratio of 1.5 and 0.9 bovine and

cunner trypsin at 15 C for 2.5 h. The juice was stored at 4 C

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a acid content of the juice (Owusu-Yaw et al., 1988). Although treatment with

supercritical carbon dioxide has been reported to give a somewhat stable cloud

in orange juice (Balaban et al, 1991), the presence of residual PME activity

reported earlier at 4 OC may cause cloud loss under certain storage conditions.

Some pectinases have also been reported to stabilize the cloud of the orange

juice to varying extents (Baker and Breummer, 1972), however a strict control of

the depolymerizing action of the pectinase is important, since a high level of

depolymerization results in the loss of juice cloud.

Treatment of PME with the cunner trypsin fraction in combination with a

temperature of 35°C was able to maintain the stability of the orange juice cloud

better than treatments with bovine trypsin at the same temperature. This

treatment can therefore serve as an alternate method in PME inactivation.

However, further studies on the effects of the treatments on other quality

attributes need to be studied.

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CHAPTER V

CONCLUSIONS

Based on the findings, the following conclusions may be made:

Digestive proteases recovered from the pancreas of the cunner fish had two

pl ranges of 6.24-6.83 and 9.66-1 0.25, suggesting the cunner trypsin fraction

possess two proteins.

The amino acid composition data revealed a polypeptide of 220 amino acid

residues, low in basic amino acids explaining the trypsin's stability at alkaline

PH.

The trypsin fraction displayed a "type 3" Km dependence on temperature,

with the highest affinity coinciding with the habitat temperature of the cunner

fish, (1 O°C).

The ammonium sulfate, acetone and affinity fractions al1 showed a great

amount of stability after storage on ice and -20°C for a period of 4 weeks

Soybean trypsin inhibitor competitively inhi bited both the cunner and bovine

trypsin. However, a mixed type of inhibition was observed for aprotinin.

The cunner trypsin fraction was more capable of hydrolyzing the native PME

and PPO better than the bovine trypsin. Conversely, bovine hydrolyzed the

heat-denatured PME and PPO better than the cunner trypsin. On storage at

4OC for 3 weeks, there was no reactivation observed for either PME or PPO

that had previously been treated with either the bovine or the cunner trypsin.

The effects of combination treatments of temperature, time and Kamel

enzyme concentration (bovine or cunner trypsin), using a 3 x 3 factorial

design, on PME gave an f of 0.92 and 095 using cunner and bovine trypsin

respectively; and on PPO an f of 0.91 and 0.94 using cunner and bovine

trypsin respectively. A complete (1 00%) inactivation of PME was possible for

some combinations; however no complete inactivation of PPO was obtained

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for al1 the levels of combination treatments. Certain combinations rather had

activatory effects on PPO.

8. The trypsin from the cunner fish was capable of upholding the cloud integrity

of orange juice better than the bovine trypsin. Cloud enhancement was

obsewed for some combination treatments on the cunner and thus, cunner

trypsin can be used as an alternate source of PME inactivation.

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