In the historic experiments that established the cyclic nature of the TCA cycle, malonate was added to minced muscle preparations. Malonate competitively inhibits succinate dehydrogenase. Which metabolic change would be expected?

• A Accumulation of fumarate with depletion of succinate
• B Accumulation of succinate with decreased formation of fumarate ✓
• C Accumulation of oxaloacetate with increased fumarate
• D Depletion of both succinate and fumarate

Explanation

Malonate is a structural analog of succinate and competitively inhibits succinate dehydrogenase, so succinate cannot be oxidized to fumarate and therefore accumulates. Because fumarate is formed only from succinate in the cycle, its production falls. Oxaloacetate would fall rather than rise, since the cycle backs up upstream, and option A reverses the actual substrate-product relationship.

Reference: Lehninger Principles of Biochemistry, 8th ed.

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