BIOMOLECULAR – BIOCHEMISTRY FACULTY OF MEDICINE

BRAWIJAYA UNIVERSITY

CARBOHYDRATE METABOLISM

Glycogenesis

ATP

DYGESTION

FOOD INTAKE : 40-45 % IS CARBOHYDRATE :

Amilopectin ( 60 % ) Glucose Fructose (fruit) Lactose (milk) Sucrose and Sacarose

GLUCOSE METABOLISM

IN THE LIVER :>Oxidation ENERGY >Glycogenesis Glycogen ( storage )>fatty acid TG VLDL >pentose pathway( HMP ) Ribose, NADPH>Glukonic Acid detoxification

IN MUSCLE :>Oxidation ENERGY >Glycogenesis Glycogen

IN ADIPOSE TISSUE :>TRIACYL GLYSEROL ( TG ) STORAGE

IN THE BRAIN :

>Oxidation ENERGY>-Ketoglutarate NH3 detoxification >Neurotransmitter

IN THE KIDNEY :

>Glycogenesis Glycogen

IN RED BLOOD CELL :

>Oxidation ENERGY >Bisphosphoglycerate( BPG ) HbO2 Dissociations >HMP pathway( Pentosa ) NADPH (Scavenger in RBC): GS-SG ------- >2G-SH H2O2 ------- >H2O + O2

(toxic)

GLUCOSE

ATPGLYCOGEN

LACTOSE

TG

TCA

HMPPATHWAY

RIBOSENADPH

URONIC PATHWAY GALACTOSE

CARBOHYDRATE METABOLISM IN GENERAL

ACETYL CoA

AA

FRUCTOSE

PYRUVATELACTATE

RNADNA

PROTEIN

RESP. CHAIN

NADH, FADH

ATP

CARBOHYDRATE METABOLISM

1. GLYCOLISIS 2. PYRUVATE OXIDATION ACETYL-

Co A 3. CYTRIC ACID CYCLE ( TCA CYCLE ) 4. GLUCONEOGENESIS 5. GLYCOGENESIS &

GLYCOGENOLISIS 6. H M P SHUNT 7. URONIC ACID PATHWAY 8. FRUCTOSE METABOLISM 9. GALACTOSE METAB. &

LACTOGENESIS 10. CARBOHYDRATE METABOLISM

DISEASE

1. GLYCOLISIS

OCCURRED IN CYTOPLASM

ENZYMATIC REACTION FOR GLUCOSE OXIDATION

AEROB : GLUCOSE PYRUVATEAN AEROB : GLUCOSE PYRUVATE LACTIC ACID

PURPOSE : 1. PRODUCE ENERGY 2. SOURCE OF PYRUVATE ATP

Lactate

anaerob

ATP PRODUCTION FROM GLYCOLYSIS:

AEROB:

SUBTRATE LEVEL = 2 X 2 = 4 ATPRESPIRATION LEVEL (NADH) = 2 X 3 = 6 ATP + 10 ATPFOR ACIVATION NEED = -2 ATPATP TOTAL = 8 ATP

AN AEROB:

NADH NADPYRUVATE ------------------>LACTATE

SUBTRATE LEVEL = 2 X 2 = 4 ATPRESPIRATION LEVEL = 0 X 3 = 0 ATP 4 ATPFOR ACTIVATION NEED = - 2 ATP ATP TOTAL = 2 ATP

2. PYRUVATE OXIDATION

PYRUVATE OXIDATION

- CONNECTION BETWEEN GLYCOLYSIS AND TCA CYCLE

- ENZYME = PYRUVATE DEHYDROGENASE COMPLEX (ENZYME IN THE MYTOCHONDRIA)

- PYRUVATE SHOULD BE TRANSPORTED IN TO MYTOCHONDRIA

ATP PRODUCTION = 2 X 3 = 6 ATP. 1 MOL GLUCOSE METABOLIZE TO 2 PYRUVATE,

2 PYRUVATE 2 ACETYL Co A 1 MOL ACETYL Co A = 3 ATP

- FIRST STEP OF THE REACTION : REACTION OF PYRUVATE WITH THIAMINE DIPHOSPHATE COENZYME

Pyruvate

Acetyl-CoA

NADH

Thiaminediphosphate

Thiaminediphosphate

3. CYTRIC ACID CYCLE

CYTRIC ACID CYCLE

FUNCTION :

1. COMMON METABOLISM PATHWAY FOR

OXIDATION OF CARBOHYDRATE, FAT AND

PROTEIN.

2. AMPHIBOLIC PATHWAY (CROSSROAD BETWEEN

ANABOLIC AND CATABOLIC PATHWAY)

3. KETO GLUTARATE ( KG) SOURCE BRAIN : DETOXICIFICATION OF NH 3

LIVER : ASPARTIC ACID FOR UREA CYCLE

4. PRODUCE ATP

MYTOCHONDRIA

ACETYL Co A

OXALOASETATE

CYTRATE

ISOCYTRATENAD+

NADH + H+

OXALOSUCCINATE

SUCINNYL C-oAGDP

GTPSUCCINATE

FAD+

FADH+H+FUMARATE

H2O

MALATE

NAD+

NADH + H+

Citrate synthase

KoA-SHH2O

Akonitase

Isocytrate dehydrogenase

CO2

-KG

Isocytrate dehydrogenase

NAD+

NADH + H+

KG dehydrogenase kompl

Succinate tiokinase

Succinate dehydrog.

Fumarase

Malate dehydrogenase

CAC

ATP PRODUCTION DURING TCA CYCLE :

1. SUBSTRATE LEVEL ……………… = 1 ATP2. OXIDATION RESPIRATION :

3 MOL NADH + H+ = 3 X 3 ATP = 9 ATP 1 MOL FADH + H = 1 X 2 ATP = 2 ATP +

TOTAL = 12 ATP

1 MOL GLUCOSE PRODUCE :

GLYCOLISIS : = 8 ATP PYRUVATE OXIDATION: = 6 ATP TCA CYCLE : = 24 ATP + TOTAL = 38 ATP

4 . GLUCONEOGENESIS

GLUCONEOGENESIS OCCURRED IN LIVER AND KIDNEY

SYNTHESIS OF CH (GLUCOSE) FROM OTHER CH

SOURCE : FATTY ACID, AMINO ACID, GLYCEROL

ENDOGEN GLUCOSE SOURCE FUNCTION: TO SUSTAIN GLUCOSE BLOOD

LEVEL DURING GLUCOSE INTAKE IS LOW : STARVATION, STRESS

IMPORTANT ROLE OF GLUCOSE : 1. BRAIN ELIMINATION OF TOXIC NH 3

2. RED BLOOD CELL ENERGY & DPG SOURCE FOR HBO2 DISSOCIATIONS

Fattyacid

TO BE CONTINUED

5. GLYCOGENESIS & GLYCOGENOLISIS

GLYCOGENESIS & GLYCOGENOLISIS

GLYCOGENESIS : GLUCOSE GLYCOGENGLYCOGENOLYSIS : GLYCOGEN GLUCOSE

GLYCOGEN : - CH SOURCE - FOUND IN THE LIVER - 5 – 6 % OF THE LIVER IS GLYCOGEN - FOOD INTAKE CH, GLYCOGEN LIVER : 10 – 15 % - GLYCOGEN STORAGE IN THE LIVER: RUN OUT AFTER 12 – 18 HOURS PASCA ABSORBTION - GLYCOGEN IS ALSO FOUND IN MUSCLE, KIDNEY AND OTHER TISSUE

GLUCOSE

GLYCOGEN

GLYCOGENSYNTHASE

GLYCOGENPHOSPHORIL

ASE

GLUCOSE1-PHOSPHATE

GLUCOKINASEGLUCOSE 6-PHOSPHATASE

GLUCOSE 6-PHOSPHATE

INSULIN

6. HMP SHUNT

HMP SHUNT FUNCTIONS:1. NADPH SOURCE ( FOR REDUCTION REACTIONS)

: + ANTIOXIDANT PROCESS

+ FATTY ACID SYNTHESIS + AMINO ACID SYNTHESIS+ STEROID SYNTHESIS+ PHOTOSYNTHESIS REACTION

2. RIBOSE SOURCE FOR NUCLEOTIDE (ATP, GTP ETC) AND NUCLEIC ACID (RNA, DNA) FOR PROTEIN SYNTHESIS

3. RIBULOSE SOURCE FOR CHLOROPLAST ORGANISM , FIXATION OF CO2.

toxic

ANTIOXIDANT PROCESS

NADPH

NADPH

SYNTHESIS OFNUCLEOTIDES,DNA AND RNA

Glucose 6-Phosphate ½ Glucose 6-Phosphate Glucose 6-Phosphate

7. URONIC ACID PATHWAY

7. URONIC ACID PATHWAY

- URIDINE DIPHOSPHATE GLUCORONATE, SOURCE FOR :

GLUCORONIDES

PROTEOGLICANS (collagen, connective tissue)

- ASCORBATE/ VIT. C SYNTHESIS (IN OTHER THAN PRIMATES AND GUINEA PIGS)

URONIC ACID PATHWAY

(Block in primateAnd guinea pigs)

8. FRUCTOSE METABOLISM

FRUCTOSE METABOLISMSOURCE OF FRUCTOSE :

- FOOD (EXOGEN SOURCE)- HEKSOSE / MONOSACHARIDE IN THE LIVER CHANGE TO FRUCTOSE (ENDOGEN)

THIS PATHWAY IS IMPORTANT FOR DIABETIC PATIENT TO OBTAIN ENERGY, SINCE GLYCOLYSIS PATHWAY IS ATTENUATED IN THIS PATIENT.

BUT IF GLUCOSE CONCENTRATION IS HIGH SORBITOL INCREASE (POLLI-OL/ALKOHOL =TOXIC)

MEMBRANE CELL DAMAGE,

REACT WITH RETINAL COLLAGEN RETINO ANGIOPATHY

LENS KATARAK LENTIS

DEF. FRUKTOKINASE ESSENSIAL FRUCTOSURIADEF. ENZ.ALDOLASE B FRUCTOSE INTOLERANCE

FRUCTOSE METABOLISM

DIET

FATTY ACIDESTERIFICATION

FATTY ACID SYNTHESIS

D-fructose

SORBITOL

9. GALACTOSE METABOLISM & LACTOGENESIS

GALACTOSE METABOLISM & LACTOGENESIS

IN HEPAR: GALACTOSE GLUCOSE PHYSIOLOGIC FUNCTION : - LACTOSE ( BREAST FEEDING ) LACTOGENESIS - GLYCOLIPID - PROTEOGLYCAN - GLYCOPROTEIN. ENZYME IN GALACTOSE METABOLISM : - GALACTOKINASE - GALACTOSE –1 PURIDIN TRANSFERASE - URIDIN DIPHOSPHOGALACTOSE 4 EPIMERASE

GALACTOSE METABOLISM

Glicolipid, proteoglycan, glycoprotein

LACTOGENESIS

10. CARBOHYDRATE METABOLISM DISEASE

CH METABOLISM DYSFUNCTION

•LACTOSA INTOLERANCE•DIABETES MELLITUS ( DM )

•GLICOGENOSIS

•PENTOSURIA

•FRUCTOSURIA ESSENTIAL

•HEREDITER FRUCTOSA INTOLERANS

•GALACTOSEMIA

LACTOSE INTOLERANCELACTOSE INTOLERANCE

OFTEN IN BABYOFTEN IN BABY

CAUSE : LACTASE INSUFISIENSYCAUSE : LACTASE INSUFISIENSY

LACTOSE IS NOT DYGESTLACTOSE IS NOT DYGEST

LACTOSE IN INTESTINELACTOSE IN INTESTINE

OSM. INTESTIN. LUMEN

WATER IN INTESTINE LUMEN

DIARHEA

FERMENTATION LACTOSEBY INTESTIN. BACTERIAL

GAS 2 : CO2, CH4 IRITANT

FLATULENCE VOMITE

DIABETES MELLITUS COMPLICATION

DIABETES MELLITUS ( DM )

TYPE I = INSULIN DEPENDENT DM (IDDM) INSULIN SHOULD BE GIVEN, SINCE PANCREAS DOES NOT PRODUCE INSULIN

OCCURRED SINCE BABY JUVENILE D.M

TIPE II = NON INS. DEPENDENT DM (NIDDM) 90% OF DM PATIENT

DIABETES MELLITUSDIABETES MELLITUS

ROLE OF INSULIN :ROLE OF INSULIN :1.1. Induce glycolysis key Induce glycolysis key

enzymeenzyme2.2. Inhibit Inhibit

gluconeogenesis key gluconeogenesis key enzymeenzyme

3.3. induce HMP shunt induce HMP shunt enzymeenzyme

4.4. increase Glut4 increase Glut4 5.5. Activate Activate

phosphodiesterase, phosphodiesterase, Glycogen sinthetaseGlycogen sinthetase

6.6. inhibit phosphorilaseinhibit phosphorilase

CONSEQUENCE IN CONSEQUENCE IN DM:DM:

1.1. GLYCOLYSIS GLYCOLYSIS 2.2. GLUCONEOGENESISGLUCONEOGENESIS3.3. HMP SHUNTHMP SHUNT4.4. Glukosa DIFFICULT to Glukosa DIFFICULT to

enter cell enter cell 5.5. Glycogenesis Glycogenesis 6.6. Glycogenolysis Glycogenolysis

HYPERGLYCEMIHYPERGLYCEMIAA

D.M PATIENT BECAUSE OF INSULIN DEF:

1. DYSFUNCTION OF CH METAB. 2. DYSFUNCTION OF LIPID METAB.

3. DYSFUNCTION OF PROTEIN METAB.

1. DYSFUNTION OF CH METABOLISM IN DM GLYCOGEN SYNTHETASE IS NOT ACTIVE >>,

PHOSPHORYLASE ENZYME TURN ACTIVE

DECREASE GLYCOGENESIS ; INCREASE GLYCOGENOLYSISDECREASE GLYCOLYSIS; INCREASE GLUCONEOGENESIS ADIPOSE TISSUE: INH IBITION OF GLUCOSE MOBILIZATION IN TO SEL GLYCOLYSIS DECREASE; HMP SHUNT DECREASE

DECREASE LIPOGENESIS ( TG FORMATION )

BLOOD SUGAR >N HYPERGLYCEMIA

GLUCOSURIA

HYPERGLYCEMIA

ATP cAMP 5-AMP

PHOSPHATASE PROTEIN KINASE ( INACTIVE )

PROTEIN KINASE ( ACTIVE )

GLYCOGEN SINTHETASE ( INACTIVE )

GLYCOGEN SINTHETASE ( ACTIVE )

GLYCOGEN

GLUCOSE-1P

GLUCOSE-6PGLUCOSE

PHOSPHORILASE A

PHOSPHORILASE B

PHOSPHATASE

PHOSPHORILASE KINASE ( ACTIVE )

ADENYLATE SICLASE PHOSPHO DIESTERASE

INSULIN ( + )

( + )

1. DYSFUNTION OF CH METABOLISM IN DM GLYCOGEN SYNTHETASE IS NOT ACTIVE >>,

PHOSPHORYLASE ENZYME TURN ACTIVE

DECREASE GLYCOGENESIS ; INCREASE GLYCOGENOLYSISDECREASE GLYCOLYSIS; INCREASE GLUCONEOGENESIS ADIPOSE TISSUE: INH IBITION OF GLUCOSE MOBILIZATION IN TO SEL GLYCOLYSIS DECREASE; HMP SHUNT DECREASE

DECREASE LIPOGENESIS ( TG FORMATION )

BLOOD SUGAR >N HYPERGLYCEMIA

GLUCOSURIA

HYPERGLYCEMIA

GLUCOSE IN URINE INCREASE URINE OSMOLALITY POLIURIINCREASE URINE VOLUME

OSMOTIC DIURESIS DEHYDRATION DEHYDRATIN CONDITION: POLIDIPSI DM PATIENT ALWAYS THIRSTY

GLUCOSE IN URINE WASTE OF ENERGY STIMULATION OF CENTRAL APETITE

DM PATIENT NEED MORE FOOD

POLIFAGIA

CHRONIC HYPERGLYCEMIA GLYCOSILATION

COLAGEN GLYCOSILATION BLOOD VESSEL ENDOTEL ATHEROSCLEROSIS

2. LIPID METABOLISM DYSFUNCTION

INSULIN DEFFICIENCY DECREASE LIPOGENESIS, INCREASE LIPOLISIS

DECREASE BODY WEIGHT

INCREASE FFA MOBILIZATION STIMULATE FFA OXIDATION IN LIVER INCREASE ACETYL CoA

KETOGENESIS KETON BODIES (ACETONE, ACETO ACETATE, HYDROXI BUTIRATE)

+

INCREASE KOLESTEROL SYNTHESIS HYPERCHOLESTEROLEMIA

GLYCOSILATION OF ATHEROSCLEROSISBLOOD VESSEL ENDOTEL

KETONEMIA

DECREASE BODY WEIGHT

KETOACIDOSIS

COMA DIABET

3. PROTEIN METABOLISM DYSFUNCTION

INSULIN DEFICIENCY TRANSMEMBRANAA TRANSPORTER DECREASE

AA MOBILIZATION IN TO CELL

PROTEIN SYNTHESIS

DECREASE TRANSCRIPTIONDECREASE TRANSLATION INHIBITION OF TISSUEDECREASE REPLICATION REGENERATIONDECREASE CELL PROLIF.

WOUND HEALING impairment

GLUCOSE

MUSCLE

ADIPOSE

VESSEL

BRAIN

PANCREAS

INSULIN

GLYCOGEN

GG

G

GLYCOGEN

TG

KIDNEY

GG

RED BLOOD CELL

GLUCOSE METABOLISM IN NORMAL CONDITION

LIVER

G IFGlucose

G

INTESTINE

GLUCOSE METABOLISM IN DIABETIC PATIENT

G

G

GLYCOGEN

G

G

GLIYCOGEN

PYRUVATE

PROTEIN

AA

KETON BODIES

ACETYL Co A

CHOLESTEROL

G GLISERAL DEHID 3P FFA

GLUCOSURIA

TG GLYS

FFA

KB

VLDL VLDL

MUSCLE

LIVER

INTESTINE

ADIPOSE

G> 180 mg/dl VESSEL

KIDNEY

STARVATIONSTARVATION

NO / DECREASE GLUCOSE INTAKENO / DECREASE GLUCOSE INTAKEALL GLUCOSE METABOLIZE BY THE TISSUEALL GLUCOSE METABOLIZE BY THE TISSUE

BLOOD GLUCOSE CONCENTRATION DECREASE BLOOD GLUCOSE CONCENTRATION DECREASE

PANCREAS : INHIBITION OF INSULIN SECRETIONPANCREAS : INHIBITION OF INSULIN SECRETIONINCREASE OF GLUKAGON SECRETIONINCREASE OF GLUKAGON SECRETION

GLYCOGENOLYSIS GLUCOSE INCREASEGLYCOGENOLYSIS GLUCOSE INCREASELOW INSULIN GLUCOSE INTO CELL LOW INSULIN GLUCOSE INTO CELL

GLUCONEOGENESIS GLUCONEOGENESIS MUSCLE ENERGY SOURCE DERIVED FROM ADIPOSE FFA MUSCLE ENERGY SOURCE DERIVED FROM ADIPOSE FFA MOBILIZATION (INCREASE LIPOLYSIS) MOBILIZATION (INCREASE LIPOLYSIS)

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