Cholesterol Metabolism
High-Yield Summary
- Cholesterol is a structural membrane component (regulates fluidity/stability) and the precursor for steroid hormones, bile acids, and vitamin D.
- Synthesized mainly in the liver, starting from acetyl-CoA, requiring NADPH.
- HMG-CoA reductase is the rate-limiting, feedback-inhibited step — inhibited by high cholesterol, stimulated by high insulin. It's the target of statin drugs (competitive inhibitors).
- Cholesterol travels through blood as cholesteryl esters within lipoproteins. LCAT converts free cholesterol into cholesteryl esters within HDL; CETP transfers cholesteryl esters between lipoproteins (e.g., HDL → LDL/VLDL).
Key Terms
- HMG-CoA reductase
- Rate-limiting enzyme of cholesterol synthesis; inhibited by cholesterol (feedback), stimulated by insulin; target of statins.
- LCAT
- Lecithin-cholesterol acyltransferase — converts free cholesterol into cholesteryl esters within HDL.
- CETP
- Cholesteryl ester transfer protein — moves cholesteryl esters between lipoprotein classes.
- Statins
- Competitive inhibitors of HMG-CoA reductase; lower cholesterol synthesis.
Cholesterol Synthesis Regulation
High cholesterol ⊣ HMG-CoA reductase; High insulin → HMG-CoA reductase
- ⊣ = Feedback inhibition
- → = Stimulation
- This is the same enzyme statins block, competitively, to lower blood cholesterol.
LCAT vs. CETP
| Enzyme | Function |
|---|---|
| LCAT (lecithin-cholesterol acyltransferase) | Free cholesterol → cholesteryl esters, within HDL |
| CETP (cholesteryl ester transfer protein) | Transfers cholesteryl esters between lipoproteins (e.g., HDL → LDL/VLDL) |
Common MCAT Trap
- Cholesterol synthesis requires NADPH (reductive biosynthesis), not NADH — same logic as fatty acid synthesis.
- HMG-CoA reductase is stimulated by insulin (fed state promotes biosynthesis) but inhibited by cholesterol itself — two different regulatory inputs, don't conflate them.
- LCAT acts within HDL; CETP moves the product OUT of HDL to other lipoproteins — these are sequential, complementary steps, not redundant ones.
Quick Recall
What is the rate-limiting enzyme of cholesterol synthesis?
What drug class targets HMG-CoA reductase, and how?
What does LCAT do?