Acetyl-CoA serves as a metabolic hub; which statement is true?

Acetyl-CoA serves as a metabolic hub; which statement is true?

• A. Cytosolic acetyl-CoA is a precursor for fatty acid and cholesterol synthesis.
• B. Acetyl-CoA cannot be used for lipid synthesis.
• C. Acetyl-CoA is only used in the TCA cycle and has no lipid role.
• D. Acetyl-CoA is directly transported across the inner mitochondrial membrane unchanged.

Answer: (A)

Acetyl-CoA links energy production and biosynthesis across cellular compartments. In the mitochondria, acetyl-CoA feeds the TCA cycle, but it cannot cross the inner mitochondrial membrane directly. To supply lipid synthesis in the cytosol, acetyl-CoA is effectively exported as citrate via the citrate shuttle; in the cytosol, citrate is cleaved back to acetyl-CoA and oxaloacetate. The cytosolic acetyl-CoA then serves as the building block for fatty acid synthesis (through acetyl-CoA carboxylase forming malonyl-CoA and subsequent steps) and for cholesterol synthesis (in the mevalonate pathway). This makes cytosolic acetyl-CoA a key precursor for both fatty acids and cholesterol. The other statements are inconsistent with how acetyl-CoA is used: it is not directly transported across the inner mitochondrial membrane unchanged, and it is indeed used for lipid synthesis, not solely for the TCA cycle.

Acetyl-CoA links energy production and biosynthesis across cellular compartments. In the mitochondria, acetyl-CoA feeds the TCA cycle, but it cannot cross the inner mitochondrial membrane directly. To supply lipid synthesis in the cytosol, acetyl-CoA is effectively exported as citrate via the citrate shuttle; in the cytosol, citrate is cleaved back to acetyl-CoA and oxaloacetate. The cytosolic acetyl-CoA then serves as the building block for fatty acid synthesis (through acetyl-CoA carboxylase forming malonyl-CoA and subsequent steps) and for cholesterol synthesis (in the mevalonate pathway). This makes cytosolic acetyl-CoA a key precursor for both fatty acids and cholesterol. The other statements are inconsistent with how acetyl-CoA is used: it is not directly transported across the inner mitochondrial membrane unchanged, and it is indeed used for lipid synthesis, not solely for the TCA cycle.