Regulation of lipid biosynthesis – Identify the key rate-limiting enzyme that controls fatty acid synthesis in animals.

Introduction / Context:
Fatty acid synthesis requires coordinated regulation to balance energy storage and expenditure. The committed, rate-limiting step is catalyzed by acetyl-CoA carboxylase (ACC), which converts acetyl-CoA to malonyl-CoA. Recognizing ACC's central regulatory position is crucial for understanding metabolic control and pharmacologic targets.

Given Data / Assumptions:

• ACC activity determines malonyl-CoA levels, the 2-carbon donor for fatty acid synthase.
• Malonyl-CoA also inhibits fatty acid oxidation by suppressing CPT I.
• ACC is regulated by phosphorylation/dephosphorylation and allosteric effectors.

Concept / Approach:
ACC is activated by citrate (polymerization) and dephosphorylation, and inhibited by phosphorylation via AMPK and by long-chain acyl-CoAs. Thus, while AMPK and phosphatases regulate ACC, they are not the rate-limiting enzyme themselves. Selecting ACC identifies the enzyme that directly sets the pace of fatty acid synthesis.

Step-by-Step Solution:

Verification / Alternative check:
Genetic and pharmacological manipulation of ACC levels/activity alters lipogenesis rates and malonyl-CoA concentrations; AMPK activators reduce lipogenesis by inhibiting ACC.

Why Other Options Are Wrong:

• AMPK and phosphatases regulate ACC but are not the committed step.
• CPT I is in fatty acid oxidation, not synthesis.
• “None of these” is incorrect because ACC is correct.

Common Pitfalls:
Confusing upstream regulators (AMPK) with the rate-limiting enzyme itself.

Final Answer:
Acetyl-CoA carboxylase (ACC)