GLYCOLYSIS & CORI’S CYCLE

Dr. Vijay Marakala, MBBS, MD.

BIOCHEMISTRY

IMS, MSU.

GLYCOLYSIS

OUTLINE Definition

Location

Reactions or pathway

Energetics

Significance

Regulation

GLYCOLYSISDefinition

Sequence of reactions that converts

GLUCOSE into PYRUVATE in the

presence of oxygen [aerobic] or

LACTATE in the absence of oxygen

[anaerobic] with the production of ATP.

Embden-Meyerhof pathway (E.M, pathway)

GLYCOLYSISLocation Major pathway for the utilization of

glucose

All the enzymes are located in the cytoplasm of cells

CYTOPLASM

GLYCOLYSISReactions

Breakdown of glucose[6-carbon] to

2 pyruvate[3-carbon]

Sequential action of 10 enzymes

Reactions can be divided into 2 phases

Istp

has

e Energy requiring phase IIn

dp

has

e Energy generating phase

GLYCOLYSISReactions

GLUCOSE

GLUCOSE-6- PHOSPHATE

ATP

ADP

Hexokinase

Reaction 1: Phosphorylation of glucose

Mg++

Ist phase

©Vijaya Marakala

GLYCOLYSISReactions

GLUCOSE-6-PHOSPHATE

FRUCTOSE-6- PHOSPHATE

Phosphohexose Isomerase

Reaction 2: Isomerization of glucose-6- phosphateIst phase

©Vijaya Marakala

GLYCOLYSISReactions

FRUCTOSE-6-PHOSPHATE

FRUCTOSE-1,6- BISPHOSPHATE

Phosphofructokinase

Reaction 3: Phosphorylation of fructose-6-phosphateIst phase

ATP

ADP

Mg++

©Vijaya Marakala

GLYCOLYSISReactions

FRUCTOSE-1,6-BISPHOSPHATE

Reaction 4: Cleavage of fructose-1,6-bisphosphateIst phase

GLYCERALDEHYDE-3-PHOSPHATE

DIHYDROXYACETONE PHOSPHATE

6 ‘C’

3 ‘C’ 3 ‘C’

Aldolase

©Vijaya Marakala

GLYCOLYSISReactions

Reaction 5: Isomerization of dihydroxyacetone phosphate Ist phase

GLYCERALDEHYDE-3-PHOSPHATE

DIHYDROXYACETONE PHOSPHATE

Phosphotriose Isomerase

• Dihydroxyacetone phosphate must be isomerized to

glyceraldehyde3-phosphate for further metabolism by

the glycolytic pathway.

• This isomerization results in the net production of two

molecules of glyceraldehyde 3-phosphate from one glucose.

©Vijaya Marakala

GLYCOLYSIS

Glucose-6-phosphate

Fructose-6-phosphate

Fructose-1,6-bisphosphate

Glyceraldehyde-3-phosphate DHAP

ATP

ADP

ADP

ATP

GlucoseSummary so far ………Hexokinase

Phosphohexose Isomerase

Phosphofructokinase

Aldolase

Phosphotriose Isomerase

©Vijaya Marakala

GLYCOLYSISReactions

Reaction 6: Oxidation of glyceraldehyde 3-phosphate IInd phase

GLYCERALDEHYDE-3PHOSPHATE DHAP

Phosphotriose Isomerase

1,3-BISPHOSPHOGLYCERATE

NAD+

NADH + H+

Glyceraldehyde-3-phosphate dehydrogenase

ETC

Pi

©Vijaya Marakala

GLYCOLYSISReactions

Reaction 7: Synthesis of 3-phosphoglycerate producing ATP IInd phase

1,3-BISPHOSPHOGLYCERATE

3-PHOSPHOGLYCERATE

ADP

ATP

Phosphoglycerate kinaseMg++

©Vijaya Marakala

GLYCOLYSISReactions

Reaction 8: Shift of the phosphate group from carbon 3 to carbon 2 IInd phase

3-PHOSPHOGLYCERATE

2-PHOSPHOGLYCERATE

Phosphoglycerate Mutase

©Vijaya Marakala

GLYCOLYSISReactions

Reaction 9: Dehydration of 2-phosphoglycerate IInd phase

2-PHOSPHOGLYCERATE

PHOSPHOENOLPYRUVATE

Enolase

H2O

Mg++

©Vijaya Marakala

GLYCOLYSISReactions

Reaction 10: Formation of pyruvate producing ATP IInd phase

PHOSPHOENOLPYRUVATE

PYRUVATE

Mg++

ADP

ATP

Pyruvate kinase

©Vijaya Marakala

GLYCOLYSISunder anaerobic condition

Reaction 11: Reduction of pyruvate to lactate IInd phase

PYRUVATE

LACTATE

NADH + H+

NAD+

Lactate dehydrogenase

Under anaerobic condition

©Vijaya Marakala

Glucose

Glucose-6-phosphate

Fructose-6-phosphate

Fructose-1,6-bisphosphate

Glyceraldehyde-3-phosphate DHAP

1,3-Bisphophoglycerate

3-phophoglycerate

2-phophoglycerate Phosphoenolpyruvate

Pyruvate

Lactate

ATPADP

ADP

ATP

NADH + H+

NADH + H+

NAD+

NAD+

ADP

ADP

ATP

ATP

GLYCOLYSISPATHWAY

©Vijaya Marakala

Energy yield from glycolysis

Reactions catalyzed by No. of ATP per glucose

Energy investment Hexokinase -1

Phosphofructokinase -1

Energy generated Glyceraldehyde-3-phosphatedehydrogenase 2NADH+H+ [3X2]

6

Phosphoglycerate kinase 2ATP 2

Pyruvate kinase 2ATP 2

Net ATP formed per glucose under aerobic condition 8

Net ATP formed per glucose under anaerobic condition 2

©Vijaya Marakala

Significanceof Glycolysis

Principal route of glucose metabolism

Ability to provide energy even under anaerobic condition

Cells lacking mitochondria glycolysis is the only source of energy example RBC

Fructose and galactose can be oxidized by this pathway

It generates precursors for biosynthetic pathway

Pyruvate Alanine

DHAP Glycerol -3-phosphate TG

Glucose -6-phosphate HMP pathway

1,3-Bisphosphoglycerate 2,3-Bisphosphoglycerate

Regulationof Glycolysis

Regulation mainly through 3 key enzymes of glycolysis

1. Hexokinase

2. Phosphofructokinase

3. Pyruvate kinase

Regulationof Glycolysis

Enzymes Activation inhibition

Hexokinase Glucose-6-phosphate

Glucokinase Insulin Glucagon

Pyruvate kinase InsulinFructose1,6-bisphosphate

Glucagon ATP cyclic-AMP

Phosphofructokinase

Insulin, AMP, Fructose-6-phosphate, Fructose-2,6-bisphosphate

GlucagonATPcitrate cyclic- AMP

Regulationof Glycolysis

Ref: Textbook of Biochemistry DM Vasudevan

CORI CYCLE

It is also known as the Lactic acid cycle.

It is a pathway links anaerobic glycolysis in muscle tissue to gluconeogenesis in the liver.

It is a process in which glucose isconverted to lactate in the muscle;

and in the liver this lactate is re-converted into glucose.

CORI CYCLE

Ref: Textbook of Biochemistry DM Vasudevan

CORI CYCLE

Carl Cori and Gerty CoriNobel prize 1947

CORI CYCLESignificance

The lactate produced in the muscle is efficiently reutilized by the body