The major source of acetyl-CoA for the synthesis of cholesterol is derived from cytosolic citrate. Examination of a hepatic cell line shows that despite a loss of expression of ATP-citrate lyase (ACL), these cells continue to have the capacity to synthesize cholesterol. The most likely explanation for this observation is related to the fact that an additional pathway is active. Which of the following enzymes is involved in this pathway?
A) acetyl-CoA synthetase
B) acetyl-CoA acyltransferase 1 (ACAT1)
C) acetoacetyl-CoA synthetase
D) HMG-CoA reductase
E) HMG-CoA synthase

Question

Quizplus · Accepted Answer

Acetoacetyl-CoA synthetase is involved in the pathway that generates acetyl-CoA from cytosolic citrate in the absence of ATP-citrate lyase. During ketogenesis, mitochondrial acetoacetate can diffuse to the cytosol where it is converted to acetoacetyl-CoA via the cytosolic enzyme, acetoacetyl-CoA synthetase. The resulting acetoacetylCoA could then serve as a direct substrate for incorporation into cholesterol. It is important to understand, however, that although this reaction process can occur, under conditions where ketogenesis is occurring in the liver the level of active HMGR would be significantly reduced.

The Major Source of Acetyl-CoA for the Synthesis of Cholesterol