The citric acid cycle is termed an amphibolic pathway as it operates both anabolically and catabolically. The cyclic reactions balance the flux of the substrates to provide an optimal concentration of NADH and ATP to the cell.
Regulation of Citric Acid Cycle
The citric acid cycle is regulated in several ways, including feedback inhibition, regulation of enzyme activities, and associated anaplerotic or cataplerotic pathways.
The primary substrate of the TCA cycle—acetyl CoA—is produced by the action of pyruvate dehydrogenase (PDH) complex. When produced in excess, acetyl CoA can inhibit the PDH complex. In addition, the high concentration of products, NADH and ATP can also strongly inhibit the PDH complex activity, subsequently inhibiting the citric acid cycle.
Similarly, the enzymes citrate synthase, isocitrate dehydrogenase, and ɑ-ketoglutarate dehydrogenase may undergo allosteric regulation via products and intermediate compounds, such as NADH, ATP, and succinyl CoA, generated during the TCA cycle.
Recycling of TCA Cycle Intermediates
In case of excess production, the TCA cycle intermediates are channeled to other pathways via a process called cataplerosis, where they act as precursors for biosynthesis. These supplied intermediates are called cataplerotic molecules. However, under conditions of limited availability, the TCA cycle can accept the intermediate metabolites from other pathways to keep the cycle running. This mechanism is termed anaplerosis, and the supplied compounds are called anaplerotic molecules.
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