TCA (Tri Carboxylic Acid) Cycle

Tri Carboxylic acid cycle essentially involves the oxidation of acetyl CoA to CO₂ and H₂O.

This is called the Tri Carboxylic Acid Cycle because in this metabolic cycle three tricarboxylic acids (citrate, cis-aconitate and isocitrate) are produced as intermediate compounds.

Another name of this cycle is Krebs Cycle, on the name of the scientist Hans Adolf Krebs, who proposed this mechanism in 1937. This cycle is also called Citric Acid Cycle.

Citric acid cycle begins with acetyl-CoA.

Acetyl-CoA is common end product of carbohydrate, fatty acid, and amino acid metabolism.

Salient Features of TCA Cycle

• The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids, because the end product of these compounds gets metabolized finally to yield energy, CO₂ and H₂O.
• This cycle not only supplies energy but also provides many intermediates chemical compounds, which are required for the synthesis of amino acids, glucose, heme etc.
• TCA cycle is the most important metabolic pathway for the energy supply to the body. About 65–70% of the ATP is synthesized in Krebs cycle and this cycle utilizes about two thirds (about 75%) of total oxygen consumed by the body.

Reaction

TCA cycle is a final metabolic pathway, the end products of Carbohydrate, lipid and protein are participated in this to finally converted into CO₂ and H₂O.

• Carbohydrates undergo glycolysis to yield pyruvate which can be taken up by mitochondria and oxidatively decarboxylated to acetyl-CoA by the pyruvate dehydrogenase enzyme complex.
• During lipolysis, triacylglycerols are converted to glycerol and free fatty acids, which are taken up by cells and transported into mitochondria, where they undergo oxidation to acetyl-CoA.
• Lastly, proteolysis of tissue proteins releases constituent amino acids, many of which are metabolized to acetyl-CoA.

Steps of TCA Cycle

Regulation of Citric Acid Cycle

Three enzymes namely citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase regulate citric acid cycle.

TCA cycle is mainly significant in production of ATP, thus in lower energy state, TCA cycle gets activated by ADP and also generally activated by the availability of substrate. Whereas the higher production of products inhibits the TCA cycle because accumulation of product binds with enzyme and inhibits their activity (Allosteric Inhibition).

TCA cycle is regulated by three important enzymes.

Amphibolic Nature of the Citric Acid Cycle

Krebs cycle is both catabolic and anabolic in nature, hence regarded as amphibolic.

• Some part of Succinyl CoA is used for the synthesis of porphyrins and heme.
• Oxaloacetate and α-ketoglutarate serve as precursors for the synthesis of aspartate and glutamate which are required for the synthesis of other non-essential amino acids, purines and pyrimidines.
• Some part of citrate is converted into acetyl CoA, which is used for the biosynthesis of fatty acids and sterols.

Energetics of TCA Cycle