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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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)
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
CH2O P
CO
C OHH
O-
3 Phosphoglycerate
CH2OH
P
CO
C OH
O-
2 Phosphoglycerate
Phosphoglycerate mutase
Dr. Ashok Kumar J; IMS; MSU
CH2OH
P
CO
C OH
O-
2 Phosphoglycerate
CH2
P
CO
C O
O-
Phosphoenolpyruvate (PEP)
Enolase
H2O
Dr. Ashok Kumar J; IMS; MSU
P
Phosphoenol
pyruvate (PEP)
CH2
CO
C O
O-
CH3
CO
C O
O-
Pyruvate
Pyruvatekinase
Substrate level phosphorylation
Dr. Ashok Kumar J; IMS; MSU
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)
Dr. Ashok Kumar J; IMS; MSU
Anaerobic Glycolysis
2 Pyruvate
2 NAD +
2 NADH+H +
4ADP
4ATP
2ADP
2ATP
Aerobic Glycolysis
Lactate dehydrogenase
Dr. Ashok Kumar J; IMS; MSU
Anaerobic glycolysis ?
Energetics of Glycolysis
Aerobic Glycolysis
8 ATPs
Anaerobic glycolysis
2 ATPs
Dr. Ashok Kumar J; IMS; MSU
Regulation
1. Hexokinase and glucokinase
2. Phosphofructokinase – 1
3. Pyruvate kinase
At 3 steps – which are irreversible
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
Pyruvate kinase
• Activated
Carbohydrate intake
• Insulin activates
and
Glucagon inhibits
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU
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
Dr. Ashok Kumar J; IMS; MSU