Glycolysis and Cori's cycle Dr. Ashok Kumar Jeppu

Glycolysis and Cori’s cycle

Dr. Ashok Kumar JeppuDepartment of BiochemistryInternational Medical School

Management and Science UniversityMalaysia

Dr. Ashok Kumar J; IMS; MSU

Glucose

• Major form of carbohydrate absorbed from the gut

• Only fuel used to any significant extent by a few specialized cells (RBC) Major fuel used by the Brain


Glycolysis(Greek :Glykys= Sweet; Lysis= Splitting)

Embden-Mayerhof pathway

Fist metabolic pathway to be

elucidated

Probably the best understood

Ubiquitous central pathway for glucose

metabolism


It is the only pathway that is taking place in all

the cells of the body.

Glycolysis is the only source of energy in

erythrocytes.

In strenuous exercise, when muscle tissue

lacks enough oxygen, anaerobic glycolysis

forms the major source of energy for muscles

The glycolytic pathway may be considered as the preliminary step

before complete oxidation

Significance of the Glycolysis Pathway


ATPADPCH2OH

CH O

C OHH

COH H

C OHH

CH OH

Glucose

CH O

C OHH

COH H

C OHH

C OHH

Glucose – 6- Phosphate

Hexokinase (Other tissues)Glucokinase (liver)


Hexokinase & GlucokinaseHexokinase

1. Extrahepatic tissues

2. High affinity for glucose (Low Km)

3. Phosphorylates other hexoses

4. Activity is not regulated by insulin

Glucokinase

1. Liver & Beta cells of Pancreas

2. Low affinity for glucose (High Km)

5. Specific for glucose

6. Activity is regulated by insulin


Phosphohexoseisomerase

PCH2O

C O

CH2OH

COH H

C OHH

C OHH

Fructose – 6- P

CH2O

CH O

C OHH

COH H

C OHH

C OHH

P

Glucose – 6- P


P6CH2O

C O

1CH2OH

COH H

C OHH

C OHH

Fructose – 6- P

O

P6CH2O

C

COH H

C OHH

C OHH

1CH2O P

Fructose – 1,6- bis P

ATP

ADP


Aldolase PhosphotrioseIsomerase

P6CH2O

CH

C OHH

O

Glyceraldehyde–3-P

OC

CH2OH

1CH2O P

Dihydroxy acetone-P

O

P6CH2O

C

COH H

C OHH

C OHH

1CH2O P

Fructose – 1,6- bis P


PCH2O

CH

C OHH

O

Glyceraldehyde–3-P

NADH+H+

NAD+

Glyceraldehyde 3 Pdehydrogenase

CH2O P

CO

C OHH

O P

1,3 bisphosphoglycerateDr. Ashok Kumar J; IMS; MSU

CH2O P

CO

C OHH

O P

1,3 bisphosphoglycerate

ATP

ADP

CH2O P

CO

C OHH

O-

3 Phosphoglycerate

Phosphoglycerate kinase

Substrate level phosphorylation


CH2O P

CO

C OHH

O-

3 Phosphoglycerate

CH2OH

P

CO

C OH

O-

2 Phosphoglycerate

Phosphoglycerate mutase


CH2OH

P

CO

C OH

O-

2 Phosphoglycerate

CH2

P

CO

C O

O-

Phosphoenolpyruvate (PEP)

Enolase

H2O


P

Phosphoenol

pyruvate (PEP)

CH2

CO

C O

O-

CH3

CO

C O

O-

Pyruvate

Pyruvatekinase

Substrate level phosphorylation


1 ATP is used

1 ATP is used

2


6 ATPs

2 ATPsProduced

2 ATPsProduced

2

2

2

2

2

2


Inhibitors of glycolysis

• Iodoacetate – glyceraldehyde -3-phosphate dehydrogenase

• Fluoride – Enolase

(Fluoride – inhibits glycolysis so it is used to collect blood sample for plasma glucose estimation)


Anaerobic Glycolysis

2 Pyruvate

2 NAD +

2 NADH+H +

4ADP

4ATP

2ADP

2ATP

Aerobic Glycolysis

Lactate dehydrogenase


Anaerobic glycolysis ?

Energetics of Glycolysis

Aerobic Glycolysis

8 ATPs

Anaerobic glycolysis

2 ATPs


BLOOD


Regulation

1. Hexokinase and glucokinase

2. Phosphofructokinase – 1

3. Pyruvate kinase

At 3 steps – which are irreversible


Phosphofructokinase - 1Activated by

*Fructose – 6 – phosphate*AMP*Fructose 2,6 bisphosphate

PFK-1 is an inducible enzymeInsulin increases and Glucagon decreases the activity

Inhibited by* Citrate*ATP


Pyruvate kinase

• Activated

Carbohydrate intake

• Insulin activates

and

Glucagon inhibits


Rapoport Lubering cycleBisphosphoglycerate shunt


CH2O P

CO

C OHHO P

1,3 bisphosphoglycerate

ATP

CH2O P

CO

C OHHO-

3 Phosphoglycerate

ADP

2,3 Phosphoglycerate

CH2O P

CO

C OH

O-

P

PPhosphatase

H2O

Mutase


Significance of Rapaport Leubering Cycle (BPG Shunt)

• 2,3-BPG combines with hemoglobin, and reduces the affinity towards oxygen. So, in presence of 2,3-BPG, oxyhemoglobin will unload oxygen more easily in tissues

• compensatory increase in 2,3-BPG in high altitudes favors oxygen dissociation. BPG is increased in fetal circulation


THANK YOU


Glycolysis and Cori's cycle Dr. Ashok Kumar Jeppu

Health & Medicine

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