In Citric acid cycle, which enzyme is inhibited by arsenite?
**Core Concept**
The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a key metabolic pathway that generates energy through the oxidation of acetate derived from carbohydrates, fats, and proteins. It involves a series of enzyme-catalyzed reactions that occur in the mitochondrial matrix. The cycle is regulated by various mechanisms, including allosteric control and substrate availability.
**Why the Correct Answer is Right**
Arsenite is a potent inhibitor of the citric acid cycle enzyme a-ketoglutarate dehydrogenase (also known as 2-oxoglutarate dehydrogenase). This enzyme catalyzes the conversion of a-ketoglutarate to succinyl-CoA, a critical step in the cycle. Arsenite binds to the lipoic acid cofactor of the enzyme, thereby preventing the formation of the acetyl-CoA thioester and inhibiting the reaction. This inhibition leads to a decrease in the citric acid cycle's ability to generate energy, resulting in a decrease in ATP production.
**Why Each Wrong Option is Incorrect**
**Option A:** Isocitrate dehydrogenase is an enzyme that catalyzes the conversion of isocitrate to a-ketoglutarate, a step preceding the inhibition site of arsenite. Therefore, it is not directly affected by arsenite.
**Option C:** Succinate dehydrogenase is a component of Complex II (succinate:quinone oxidoreductase) of the electron transport chain and is not directly involved in the citric acid cycle. It is not inhibited by arsenite.
**Option D:** Aconitase is an enzyme that catalyzes the conversion of citrate to isocitrate, which occurs earlier in the citric acid cycle. It is not inhibited by arsenite.
**Clinical Pearl / High-Yield Fact**
Arsenite poisoning can lead to severe metabolic acidosis due to the inhibition of the citric acid cycle and the subsequent decrease in ATP production. This can result in a range of clinical symptoms, including nausea, vomiting, and respiratory failure.
**✓ Correct Answer: B. a ketoglutarate Dehydrogenase**