Krebs Cycle

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Also called tri-carboxylic acid (TCA) cycle. The TCA cycle is both catabolic and anabolic. It is catabolic as all macromolecules when broken down enter to TCA cycle for energy production. And it is anabolic as TCA intermediates are used for synthesis of other compounds. Examples: Succinyl Co-A for heme synthesis, Oxaloacetate for Asparagine synthesis, α- ketoglutarate for Glutamine synthesis.

TCA cycle is one of the vital cycle as there is no compatibility of life with TCA cycle enzyme deficiencies. It has no hormonal control unlike other anabolic and catabolic pathways. Rather it is controlled by energy state of cell and availability of oxaloacetate.

Anaplerotic reaction:

These are the reactions which replenish TCA cycle intermediates.

TCA cycle image:

Enzymes of TCA cycle

All enzymes of TCA cycle are present at mitochondrial matrix except succinate dehydrogenase (present at inner mitochondrial membrane).

Rate limiting enzymes of TCA:

  • Citrate synthase
  • Isocitrate dehydrogenase
  • α- ketoglutarate dehydrogenase

There are four dehydrogenase and one kinase.

DehydrogenaseKinase
Oxidative decarboxylation:
α- ketoglutarate dehydrogenase
Isocitrate dehydrogenase

Oxidation:
Succinate dehydrogenase
Malate dehydrogenase  
Succinate thiokinase. It is the only substrate level phosphorylation of TCA cycle.

Energetics of TCA cycle:

TCA cycle produces 3 NADH, 1 FADH2, 1 GTP = 3X2.5 + 1X1.5+ 1 = 10 ATP.

TCA cycle occurs in aerobic state but no enzymes of TCA cycle require oxygen. In absence of oxygen, produced NADH, FADH2 will not be able to enter electron transport chain leading to depletion of NAD/FAD eventually stopping the TCA cycle.


References:

  1. Harper’s Illustrated Biochemistry Thirty Second Edition.
  2. Lippincott’s Illustrated Reviews – Biochemistry.

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