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Which enzyme acts as the rate-limiting factor of the TCA Cycle?

  1. Fructose bisphosphatase 2

  2. Phosphofructokinase (PFK)

  3. Isocitrate dehydrogenase

  4. Alpha galactosidase

The correct answer is: Isocitrate dehydrogenase

The TCA Cycle, also known as the Citric Acid Cycle or Krebs Cycle, is a critical metabolic pathway involved in generating energy through the oxidation of acetyl-CoA. The enzyme that acts as the rate-limiting factor in this cycle is isocitrate dehydrogenase. This enzyme catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, which is a key regulatory step in the cycle. Isocitrate dehydrogenase plays a crucial role because it is sensitive to the energy status of the cell; it is activated by substrates such as ADP and inhibited by ATP and NADH. This regulatory mechanism allows the TCA Cycle to adjust its speed according to the cell's energy demands, thus making isocitrate dehydrogenase a significant control point in the pathway. In contrast, the other enzymes listed serve different functions in metabolism. Fructose bisphosphatase 2 is involved in gluconeogenesis, whereas phosphofructokinase is a central regulatory enzyme in glycolysis, and alpha galactosidase is related to the metabolism of certain carbohydrates. None of these enzymes are directly involved in regulating the TCA Cycle, highlighting why isocitrate