GLIKOLISIS

Fate of glucose

Completely oxidized to CO2 and H2O.Cellular respiration

Converted to lactate.Cori cycle converts lactate back to glucose.

Converted to acetyl CoA.Enters Kreb’s cycle* or is used to synthesize fat.

Converted to other monosaccharidesPentose phosphate shunt

Stored as glycogen in muscles and liver.

Glucose MetabolismGlucose Metabolism

GlycolysisGlycolysisWhat is glycolysis?

Ten step metabolic pathway to convert glucose into two molecules of pyruvate and two molecules each of NADH and ATP.

All carbohydrates to be catabolized must enter the glycolytic pathway.

Glycolysis is central in generating both energy and metabolic intermediaries.

Also known as Embden-Meyerhof-Parnas (EMP) pathway

Glycolysis has two stages.Glycolysis has two stages.

(i) An energy investment phase. Reactions, 1-5. Glucose to two glyceraldehyde -3-phosphate molecules. 2 ATPs are invested.

(ii) An energy payoff phase. Reactions 6-10. two glyceraldehyde 3-phosphate molecules to two pyruvate plus four ATP molecules.

-- A net of two ATP molecules overallplus two NADH.

Why oxidize glucose in stages?

G˚’ = -686 kcal/mol

• Direct combustion of glucose occurs at temperatures incompatible with life.

Glycolysis: Step 1

Hexokinase and glucokinase catalyzes irreversible phosphorylation of glucose (G-6-P).

OH

OH

H

OH

H

OHH

OH

CH2

O

PO32-

D-Glucose-6-phosphate( G-6-P )

OH

OH

H

OH

H

OHH

OH

CH2OH

D-Glucose

ATP ADP

Mg2+

hexokinase,glucokinase

Glycolysis: Step 2

Phosphoglucoisomerase converts G-6-P into fructose-6-phosphate (F-6-P).

Makes C1 of hexose available for phosphorylation.

OH

CH2OH

H

H OH

OH H

O

CH3

O

PO32-

D-Fructose-6-phosphate( F-6-P )

OH

OH

H

OH

H

OHH

OH

CH2

O

PO32-

D-Glucose-6-phosphate( G-6-P )

phosphoglucoisomerase

Glycolysis: Step 3

Phosphofructokinase (PFK-1) catalyzes irreversible phosphorylation of F-6-P to form fructose-1,6-diphosphate (F-1,6-DP).

OH

CH2

H

H OH

OH H

O

CH3

OO

PO32-PO3

2-

D-Fructose-1,6-diphosphate( F-1,6-DP )

OH

CH2OH

H

H OH

OH H

O

CH3

O

PO32-

D-Fructose-6-phosphate( F-6-P )

ATP ADP

Mg2+

phosphofructokinase

Glycolysis: Step 4

Fructose diphosphate aldolase catalyzes the cleavage of F-1,6-DP to form dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G-3-P).

CH2O

CH

OHCH

O

PO32-

D-Glyseraldehide-3-phosphate

H2C

O

HOH2C

O

Dihydroxy acetone phosphate

PO32-

( DHAP )( G-3-P )

+

fructosediphosphate

aldolase

OH

CH2

H

H OH

OH H

O

CH3

OO

PO32-PO3

2-

D-Fructose-1,6-diphosphate( F-1,6-DP )

Glycolysis: Step 5

Triose phosphate isomerase converts DHAP to G-3-P.

G-3-P continues through glycolysis.

Triosa phosphate isomerase

H2C

O

HOH2C

O

Dihydroxy acetone phosphate

PO32-

( DHAP )

CH2O

CH

OHCH

O

PO32-

D-Glyseraldehide-3-phosphate( G-3-P )

Glycolysis: Step 6

G-3-P dehydrogenase catalyzes oxidation and phosphorylation of G-3-P to form 3-Phosphoglyceroil phosphate

CH2O

CH

OHCH

O

PO32-

D-Glyseraldehide phosphatedehydrogenase

NADH + H+

NAD+Pi

D-Glyseraldehide-3-phosphate

CH2O

CH

OHC

O

PO32-

3-Phosphoglyceroil phosphate

O

PO32-

Glycolysis: Step 7

Phosphoglycerate kinase (PGK) transfers phosphate from 3-PGP to ADP to form ATP (substrate-level phosphorylation) and 3-phosphoglycerate (3-PG).

CH2O

CH

OHC

O

PO32-

3-Phosphoglyceroil phosphate

O

PO32-

CH2O

CH

OHC

O

PO32-

O-

3-Phosphoglycerate

ADP ATP

Mg2+

Phosphoglycerate kinase

Glycolysis: Step 8

3-PG is converted to 2-PG by phosphoglycerate mutase.

Moving phosphate closer to carboxyl group makes molecule more unstable ( G) and thus more likely to transfer phosphate to another substrate.

CH2O

CH

OHC

O

PO32-

O-

3-Phosphoglycerate

CH2OH

CH

OC

O

O-

PO32-

2-Phosphoglycerate

Mg2+

Phosphoglycerate mutase

Glycolysis: Step 9

Dehydration of 2-PG to form phosphoenolpyruvate (PEP) is catalyzed by enolase.

Traps PEP in enol form (tautomer), which is very unstable facilitating transfer of phosphate to ADP in step 10.

CH2OH

CH

OC

O

O-

PO32-

2-Phosphoglycerate

CH2

C

OC

O

O-

PO32-

Phosphoenolpyruvate

K+,Mg2+

enolase

Glycolysis: Step 10

Pyruvate kinase catalyzes irreversible transfer of phosphate from PEP to ADP to form ATP (2nd substrate-level phosphorylation) and pyruvate.

CH2

C

OC

O

O-

PO32-

Phosphoenolpyruvate

ADP ATPMg2+

Pyruvate kinase

CH3

C

C

O

O-

O

Pyruvate

PyruvatePyruvate

Alcohol AnaerobicAlcohol Anaerobic FermentationFermentation GlycolysisGlycolysis

Aerobic GlycolysisAerobic Glycolysis

What Happens to Pyruvate?

-PyruvatePyruvate can be further processed:

a) anaerobically : to lactatelactate in muscle

b) anaerobically : to ethanolethanol (fermentation)

c) aerobically to CO2 and H2O via the citric acid cycle.

a) Lactic Acid Fermentation

• Occurs in muscles.

O

O

O-

pyruvateOH

O

O-

lactate

NADH + H+ NAD+

Siklus Cory

Liver Glycogen

Blood GlucoseLactate acid

Muscle Glycogen

b) Alcoholic Fermentation

O

O

O-

pyruvate

+ H+

CO2

O

acetaldehyde

HO

ethanol

NADH+H+ NAD+

1 2

1. Pyruvate decarboxylase – irreversible

2. Alcohol dehydrogenase – reversible

Note : NADH used up

Glikogen

Glukosa1-fosfat

Glukosa6-fosfat

Fruktosa6-fosfat

Fruktosa1,6-difosfat

Gliseraldehida3-fosfat

OH

H

H

OH

H

OHH

OH

CH2OH

O

D-Galaktosa

OH

CH2OH

H

OH H

H OH

CH2OHO

D-Fruktosa

OH

OH

H

OH

H

OHH

OH

CH2OH

D-Glukosa

OH

OH

H

OH

OH

HH

OH

CH2OH

D-manosa

UDP-galaktosa

UDP-glukosa

Manosa 6-fosfat

Fruktosa 1-fosfat

Gliseraldehida + Dehidroksiaseton fosfat

Metabolism of Other Sugars

ATP

ATP

ATP

ATP

ATP

Pi

fosforilase

Fosfogluko-mutase

heksokinase

Fosfomano-isomerase

heksokinase

heksokinase

fruktokinase

triosa kinase

triosa fosfatisomerase

Fruktosa fosfat aldolase

SummarySummary GlucoseGlucoseof Reactionsof Reactions 2 ATP 2 NADH 2 pyruvate 2 NADH 2 NADH anaerobicanaerobic anaerobicanaerobic 2 ethanol + CO2 2 lactate

2 CO2 + 2 acetyl CoA

  O2 aerobicaerobic

4 CO2 + 4 H2O

Summary of Energy Relationship for Summary of Energy Relationship for GlycolysisGlycolysis  

Input = 2 ATP 1. glucose + ATP glucose-6-P 2. fructose-6-P + ATP fructose 1,6

diphosphateOutput = 4 ATP + 2 NADHa. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+ 2 (3-phosphoglyceroil phosphate) + 2 NADHb. 2 (3-phosphoglyceroil phosphate) + 2 ADP 2 (3-P-glycerate) + 2 ATPc. 2 PEP + 2 ADP 2 pyruvate + 2 ATPNet = 2 ATP and 2 NADH