1. Citric Acid cycle or
Tricarboxylic Acid cycle
or Krebs Cycle Dr. Humaira Aman

2.  At the end of the lecture,
students would be able
to:
 Define krebs cycle.
 Describe briefly the reactions of
cycle.
 Explain the total energy
produced by the TCA cycle.

3. Overview
 Final pathway for
the oxidative
metabolism of
amino acids,
carbohydrates and
fatty acids.
 Krebs in
mitochondrial matrix

4. In Mitochondria
In Cytosol

5. Overall
goal
 Makes ATP
 Makes NADH
 Makes FADH2

6. REACTIONS OF TCA CYCLE
 “The wheel is turnin’
and the sugar’s a
burnin’”

7. A.OXIDATIVE DECARBOXYLATION OF
PYRUVATE

8. Reaction of pyruvate dehydrogenase complex (PDC)
 2 per glucose (all of Krebs)
 Oxidative decarboxylation
 Makes NADH

9. Pyruvate dehydrogenase Complex (PDC)
It is a multi-enzyme complex containing three enzymes :
E-1 : Pyruvate dehydrogenase, uses Thiamine pyrophosphate as
cofactor bound to E1
E-2 : Dihydrolipoyl transacetylase, Lipoic acid bound, CoA as
substrate
E-3 : Dihydrolipoyl Dehydrogenase FAD bound, NAD+
as substrate

10. REGULATION OF PYRUVATE DEHYDROGENASE
COMPLEX

11. B. SYNTHESIS OF CITRATE

12. Citrate synthase
1. Binding of Oxaloacetate to the enzyme results in conformational change
which facilitates the binding of the next substrate, the acetyl Coenzyme A.
There is a further conformational change which leads to formation of
products.

13. Aconitase: This enzyme catalyses the isomerization
reaction by removing and then adding back the water ( H
and OH ) to cis-aconitate in at different positions. Isocitrate
is consumed rapidly by the next step thus deriving the
reaction in forward direction.
C. ISOMERIZATION OF CITRATE

14. D. OXIDATION & DECARBOXYLATION OF
ISOCITRATE

15. Isocitrate dehydrogenase:
 Oxidative decarboxylation
 Rate limiting step. Enzyme activated by ADP and Ca++ and inhibited by
ATP and NADH

16. E. OXIDATION & DECARBOXYLATION OF α-KETOGLUTARATE

17. α- Ketoglutarate dehydrogenase complex: This is a complex of
different enzymatic activities similar to the pyruvate dehydrogenase
complex. It has the same mechanism of reaction with E1, E2 and E3
enzyme units. NAD+ is an electron acceptor.

18. F. CLEAVAGE OF SUCCINYL CoA

19. Succinyl CoA synthatse:

20. G. OXIDATION OF SUCCINATE

21. Succinate Dehydrogenase: Oxidation of succinate to fumarate. This is
the only citric acid cycle enzyme that is tightly bound to the inner
mitochondrial membrane. It is an FAD dependent enzyme.

22. H . HYDRATION OF FUMARATE catalyzed by Fumarase: Hydration of
Fumarate to malate.

23. I. OXIDATION OF MALATE

24. Malate dehydrogenase: Oxidation of malate to oxaloacetate: It is an
NAD+
dependent enzyme. Reaction is pulled in forward direction by the
next reaction (citrate synthase reaction) as the oxaloacetate is depleted
at a very fast rate.