cholesterol metabolism

Meaning: Cholesterol metabolism covers how cells make, move, use, and remove cholesterol. Synthesis starts from acetyl-CoA and runs through HMG-CoA to mevalonate, then isoprene units and squalene, ending in the four-ring sterol. The rate-limiting step is HMG-CoA reductase, which uses NADPH. Cholesterol adjusts membrane fluidity and is the precursor of steroid hormones, bile salts, and vitamin D. Animal cells cannot oxidize the ring to CO₂, so it leaves mainly as bile salts and as cholesterol in bile.

On the MCAT: Expect questions on regulation. High cellular cholesterol lowers HMG-CoA reductase activity by feedback inhibition, reduced transcription (through SREBP), and enzyme degradation. Insulin favors the active, dephosphorylated enzyme; glucagon favors the phosphorylated, inactive form. Dietary cholesterol suppresses, but does not abolish, synthesis. For transport, LDL delivers cholesterol to cells by LDL receptor-mediated endocytosis, and HDL returns it to the liver. Defective LDL receptors raise blood LDL and, because less cholesterol enters cells, synthesis stays high.

Common confusion: LDL and HDL are lipoprotein particles, not different kinds of cholesterol; the molecule is the same. Also, cholesterol and fatty acid synthesis share acetyl-CoA, but they are separate pathways with different rate-limiting enzymes (HMG-CoA reductase versus acetyl-CoA carboxylase).