Carbohadrate metabolism MBBS Follow respective lectures

1. CARBOHYDRATE
METABOLISM
Lecture 2
Dr. Vaneet Kaur

2. • (3.4) Define and differentiate the pathways of glycolysis
• Objectives
• Describe the overall purpose of glycolysis, its reactants and products,
its cellular localization, and its tissue distribution.
• Describe the roles of hexokinase/glucokinase, phosphofructokinase-1
(PFK-1), and pyruvate kinase in glycolysis
• Compare and contrast aerobic and anaerobic glycolysis in terms of
the tissues in which they occur, reactants and products, purposes,
and the conditions in which they occur

3. GLYCOLYSIS ( EMBDEN MEYERHOF PATHWAY)
• Oxidation of glucose
• Only pathway which takes place in the cytoplasm of almost all cells
• End product- Pyruvate in Aerobic glycolysis & Lactate in anaerobic
glycolysis
• Significance:
• Source of energy ( only source of energy in erythrocytes as they lack
mitochondria)
• Provides carbon skeletons for synthesis of nonessential amino acids &
glycerol
• Pathway for utilization of not only glucose but also other sugars like
fructose, galactose

4. • Heart muscle has poor glycolytic ability and poor survival under
conditions of ischaemia as it is adapted for aerobic performance
• In strenuous exercise, when muscle lacks oxygen, anaerobic glycolysis
forms the major source of energy for muscles

5. Stages of glycolysis
• Stage 1 ( Investment stage)
• Reactions catalyzed by
• Glucokinase/hexokinase ( irreversible reaction)
• Phosphoglucoisomerase
• PFK-1( irreversible reaction)
• Stage 2 ( Splitting phase)
• Aldolase
• Triose phosphate isomerase

6. • Stage 3( Energy generation stage)
• Reactions catalyzed by
• Glyceraldehyde phosphate dehydrogenase( example of Oxidative
phosphorylation)
• Phosphosphoglycerate kinase
• Phosphosphoglycerate mutase
• Enolase
• Pyruvate kinase ( irreversible reaction)
• Substrate level phosphorylation examples--(Phosphosphoglycerate
kinase, Pyruvate kinase )

8. Hexokinase
• Present in all the tissues
• It acts on all hexoses
• It has low km ( high affinity) for
glucose
• It supplies glucose to tissues even
in presence of low blood glucose
conc
• It acts on both the anomers of
glucose – α & β
Glucokinase
• Present in liver and pancreatic
islet cells
• It acts only on glucose
• It has high km ( low affinity) for
glucose
• It operates only when blood
glucose levels are high
• It acts only on α –D glucose

9. Inhibitors of glycolysis
• Name of enzyme Inhibitor
• Glyceraldehyde 3 phosphate DHG Iodoacetate
• Phosphoglycerate kinase Arsenate
• Enolase Fluoride
• Note: Enolase requires Mg ions. By removing mg ions, fluoride will inhibit
enolase and would stop glycolysis
• FBS ( Fasting blood sugar vial in which sample for blood sugar has to be
collected , is prepared by putting sodium fluoride & potassium oxalate in
the ratio of 1:3)
• This stops glycolysis and helps in correct estimation of blood glucose levels

11. Bioenergetics of aerobic glycolysis
Enzyme Source Number of ATPs gained or lost
Hexokinase/glucokinase - -1
PFK-1 - -1
Glyceraldehyde 3 phosphate DHG
1,3 Phosphoglycerate kinase
Pyruvate kinase
2 NADH
2ATP
2ATP
2.5x2=5
2
2 ( Net gain ---9-2=7 ATPs)

12. Anaerobic glycolysis
• Occurs in tissues which lack mitochondria
• RBCs, lens, cornea, renal medulla
• Pyruvate is converted into lactate by Lactate DHG
• The NADH utilized in this reaction is derived from conversion of
Glyceraldehyde 3 phosphate DHG into 1,3 Bisphosphoglycerate ( can
be seen in the diagram in adjacent slide)
• This occurrence of uninterrupted glycolysis is important in skeletal
muscle during strenuous exercise where oxygen supply is limited

14. Bioenergetics of anaerobic glycolysis
Enzyme Source Number of ATPs gained or lost
Hexokinase - -1
PFK-1 - -1
1,3 Phosphoglycerate kinase ATP +2
Pyruvate kinase ATP +2 ( Net gain =2 ATPs) End product
is lactate

15. 2,3 Bisphosphoglycerate shunt( Rappaport
leubering cycle)
• In erythrocytes of mammals, the step catalyzed by phosphoglycerate
kinase is bypassed
• Bisphosphoglycerate mutase catalyses the conversion of 1,3
bisphosphoglycerate to 2,3 bisphosphoglycerate which is converted
into 3, phosphoglycerate by 2,3 bisphosphoglycerate phosphatase(
see the next slide for the diagram)

17. Significance of 2,3 BPG shunt
• There is no production of ATP during glycolysis
• So, advantageous to RBCs since it allows glycolysis to proceed when
the need for ATP is minimum
• 2, 3 BPG which is present in high concentration combines with Hb,
causing a decrease in the affinity of Hb for oxygen
• This helps in unloading of oxygen to tissues
• The levels of 2,3 BPG are raised at high altitude, in hypoxic
conditions, anaemia and in fetal tissues. This allows increased supply
of oxygen to tissues

18. Irreversible reactions of glycolysis
• Are catalysed by the following enzymes—
• Hexokinase/ glucokinase
• Phosphofructokinase 1
• Pyruvate kinase

19. Regulation of glycolysis
• Glucokinase- It has high Km for glucose. So it will act when blood glucose
levels are high.
• So when blood glucose levels are low, glucose is made available to the
brain .
• Hexokinase is inhibited by glucose 6 phosphate
• Phosphofructokinase -1 ( PFK-1)
• Rate limiting enzyme of glycolysis
• ATP and citrate are inhibitors ( when end product is in plenty, enzyme is
inhibited)
• AMP is the activator ( Rate of glycolysis increases when the Product of
glycolysis ie. ATP is less)

20. • Fructose 2,6 Bisphosphate- It is formed from fructose 6 phosphate by
Phosphofructokinase -2 (PFK-2)
• When glucose is in excess, PFK-2 is activated and it stimulates PFK-1,
which in turn stimulates glycolysis ( use of glucose for energy)
• When glucose levels are low, PFK-2 is inactivated which results in
activation of Fructose 1,6 bisphosphatase ( FBPase 1) which activates
gluconeogenesis ( production of glucose )
• Can be understood from the diagram in next slide

23. • Pyruvate kinase- When energy is in plenty, glycolysis is inhibited
• Pyruvate kinase is active when dephosphorylated and inactive when
phosphorylated
• Role of hormones
• Insulin favours glycolysis and glucagon inhibits glycolysis