acyl-CoA

Meaning: An acyl-CoA is an acyl group (a fatty acid chain) attached to the sulfur of coenzyme A through a thioester bond. This bond is high in energy, so the fatty acid is "activated." Acyl-CoA synthetase forms it in the cytosol, at the outer mitochondrial membrane, using ATP. Long-chain acyl-CoA cannot cross the inner mitochondrial membrane on its own. It crosses by the carnitine shuttle: CPT I swaps CoA for carnitine, a translocase moves the acylcarnitine in, and CPT II restores acyl-CoA in the matrix. There β-oxidation shortens it by two carbons per cycle, giving FADH₂, NADH and acetyl-CoA.

Equation: fatty acid + CoA-SH + ATP → acyl-CoA + AMP + PPi. CoA-SH is free coenzyme A, ATP is adenosine triphosphate, AMP is adenosine monophosphate, and PPi is pyrophosphate. Each is counted in mol. PPi is then hydrolyzed, which pulls the reaction forward.

On the MCAT: Passages describe fasting, exercise or a carnitine or CPT deficiency and ask what happens to β-oxidation. Malonyl-CoA, made during fatty acid synthesis, inhibits CPT I, so synthesis and oxidation do not run together. Expect to count ATP: activation costs 2 ATP equivalents.

Common confusion: Acetyl-CoA is the two-carbon acyl-CoA, but acyl-CoA usually means a longer chain. Activation uses one ATP molecule but costs two ATP equivalents, because ATP becomes AMP, not ADP. The carnitine shuttle is needed mainly for long-chain fatty acids.