An experiment is designed to study the coupling of the citric acid cycle and electron transport. Isolated mitochondria are provided with pyruvate and oxygen. It is observed that a high intramitochondrial NADH/NAD+ ratio, which can be caused by an ETC defect, strongly inhibits the citric acid cycle.
An elevated NADH/NAD+ ratio directly causes allosteric inhibition of which of the following key regulatory enzymes?
- Isocitrate dehydrogenase (correct answer)
- Succinate thiokinase
- Fumarase
- Aconitase
Explanation: The citric acid cycle is tightly regulated by the energy state of the cell, reflected by ratios like ATP/ADP and NADH/NAD+. High levels of NADH, indicating a state of high energy or a block in the ETC, directly inhibit several key dehydrogenases. The most important regulated steps inhibited by NADH are pyruvate dehydrogenase, isocitrate dehydrogenase, and the α-ketoglutarate dehydrogenase complex. Of the options provided, isocitrate dehydrogenase is a major regulatory point that is allosterically inhibited by NADH.