Lecture slides for medical students on TCA cycle.

1. Department of Biochemistry, NGMC, Nepal
Thursday, August 18,
2016
Rajesh Chaudhary
1
TCA
Cycle
Krebs
Cycle
Citric
acid
Cycle

2. Citric acid cycle
Final pathway for metabolism of carbohydrate, proteins
and fat.
The citric acid cycle occur totally in mitochondria.
Has central role in gluconeogenesis, lipogenesis, and
interconversion of amino acids.
Occurs in most of the tissues but in liver its activity is
significant.
Defects in enzymes of TCA cycle has been linked to the
severe neurological diseases because of the severe
impairment in ATP production. Thursday, August 18,
2016
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3. Thursday, August 18,
2016
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Final metabolic pathway
for carbohydrate, protein
and lipids.

4. Citric acid cycle
 Hyperammonemia in advance liver disease leads to loss of
consciousness, coma and convulsions as a result of impaired TCA
cycle.
 Ammonia depletes TCA cycle intermediates by withdrawing
a-ketoglutarate for the formation of glutamate and glutamine
and also inhibits the oxidative decarboxylation of a-
ketoglutarate.
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2016
Rajesh Chaudhary
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5. Catalytic role of
Oxaloacetate in TCA
cycle
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2016
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Only small amount of
oxaloacetate is required
for the oxidation of large
quantity of Acetyl-CoA.

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2016
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Role of poison
Fluoroacetate
3 isoenzymes of isocitrate
dehydrogenase:
1. One that uses NAD+:
found only in
mitochondria.
2. Other two uses NADP+:
found in mitochondria
+ Cytoplasm.
Poison
Arsenite
Succinate
Thiokinase /
2 isoenzymes are present
in liver and kidney: one
specific for GDP and
another for ADP
Requires
NAD+

7. 7
Role of poison
Fluoroacetate
Fluroacetate + acetyl-CoA  Fluroacetyl-CoA, then condenses
with oxaloacetate to form flurocitrate. Flurocitrate inhibits
aconitase resulting in accumulation of Citrate.

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2016
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3 isoenzymes of
isocitrate
dehydrogenase:
1. One that uses NAD+:
found only in
mitochondria.
2. Other two uses NADP+:
found in mitochondria
+ Cytoplasm.

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2016
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Requires same cofactors as
that of pyruvate
dehydrogenase. Eg.
NAD+, FAD, CoA
Poison
Arsenite

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2016
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Same sequence of chemical
reactions that occurs in b-
oxidation of Fattyacids.

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12. Total reactions of TCA cycle
 Total no. of reactions: 8
 Total carbon dioxide released: 2
 Total no. of reversible reactions: 5 reactions (Reaction no.: 2,
5, 6, 7, 8)
 Types of reactions: 1. Condensation, 2 (a). Dehydration, 2 (b).
Hydration, 3. Oxidative decarboxyation, 4. Oxidative
decarboxyation, 5. Substrate level phosphorylation, 6.
Dehydrogenation, 7. Hydration, 8. Dehydrogenation.
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2016
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13. Product of one turn of TCA cycle
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2016
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3 NADH
1 FADH2
1 GTP or ATP
2 CO2

14. Energetics of TCA cycle
No. of ATP generated by oxidation of 3 NADH = 9
No. of ATP generated by oxidation of FADH2 = 2
No. of ATP generated from GTP = 1
Total ATP generated from oxidation of 1 molecule of
Acetyl-CoA = 12
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2016
Rajesh Chaudhary
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15. Vitamins play key role in TCA cycle
Riboflavin in the form of FAD.
Niacin in the form of NAD.
Thiamin / Vitamin B1
Pantothenic acid
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2016
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16. Role of TCA cycle in anabolic pathways
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2016
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17. Anaplerotic reactions
Reactions that make sure that intermediates of TCA
cycle are replenished when consumed during anabolic
phase.
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2016
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18. Regulation of TCA
cycle
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2016
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TCA cycle is regulated at 3
exergonic steps:
1. Substrate availability
2. Inhibition by accumulating
product
3. Allosteric feedback
inhibition of the enzymes
that catalyze early steps of
the reactions

19. Feeder pathways
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2016
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20. Feeder pathways
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21. References
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