citric acid cycle

Department of Biochemistry, NGMC, Nepal

Thursday, August 18,

2016Rajesh Chaudhary

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TCA Cycle

Krebs Cycle

Citric acid Cycle

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,


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Final metabolic pathway

for carbohydrate, protein

and lipids.

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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Catalytic role of

Oxaloacetate in TCA

cycle



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Only small amount of

oxaloacetate is required

for the oxidation of large

quantity of Acetyl-CoA.



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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+

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Role of poison

Fluoroacetate

Fluroacetate + acetyl-CoA Fluroacetyl-CoA, then condenses

with oxaloacetate to form flurocitrate. Flurocitrate inhibits

aconitase resulting in accumulation of Citrate.



8 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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Requires same cofactors as

that of pyruvate

dehydrogenase. Eg.

NAD+, FAD, CoA

Poison

Arsenite



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Same sequence of chemical

reactions that occurs in b-

oxidation of Fattyacids.



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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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Product of one turn of TCA cycle



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3 NADH

1 FADH2

1 GTP or ATP

2 CO2

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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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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Role of TCA cycle in anabolic pathways



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Anaplerotic reactions

Reactions that make sure that intermediates of TCA

cycle are replenished when consumed during anabolic

phase.



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Regulation of TCA

cycle



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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

Feeder pathways



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Feeder pathways



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References



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citric acid cycle

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