HDL-Cholesterin: the pathway in the body

HDL-Cholesterin is part of the pathway “Cholesterol and lipoproteins”. This page shows the whole pathway; the station of HDL-Cholesterin is highlighted.

Where this laboratory value sits: HDL — picks up cholesterol. Cells pass surplus cholesterol via ABCA1 to the carrier protein ApoA-I. The enzyme LCAT esterifies it; a flat disc thus becomes a spherical HDL particle. Source 5

In brief

Cholesterol is a lipid with a ring structure that the body mainly makes itself, above all in the liver. It is a building block of every cell membrane and travels through the blood in lipoproteins such as LDL and HDL.

The pathway step by step

1. Acetyl-CoA → HMG-CoA HMG-CoA synthase Three acetyl units are joined to form HMG-CoA. The same intermediate also occurs in ketone body metabolism, but there it is formed in the mitochondrion. Source 2
2. HMG-CoA → Mevalonate HMG-CoA reductase · NADPH HMG-CoA reductase is the slowest step of the pathway. Here, via the protein SREBP-2, the cell regulates how much it produces and how many LDL receptors it makes. Source 2
3. Mevalonate → Cholesterol Squalene pathway · Oxygen, NADPH Some twenty further steps lead to squalene and from it to the ring structure. Cholesterol is a component of every cell membrane and the starting material for steroid hormones, vitamin D and bile acids. Source 1, 2
4. Cholesterol in the gut → Into the gut cell NPC1L1 The transport protein NPC1L1 moves cholesterol from the gut lumen into the cell. Part of it is pumped straight back out via ABCG5 and ABCG8. Source 3
5. Chylomicrons → Remnants to the liver Lipoprotein lipase Along the way, lipoprotein lipase removes the triglycerides. The liver takes up the remaining cholesterol-rich remnants. Source 1
6. Remnants to the liver → VLDL The liver packages fats and cholesterol into VLDL particles and releases them into the blood. The carrier protein on them is ApoB-100. Source 1
7. VLDL → LDL Lipoprotein lipase Triglycerides are also removed from VLDL along the way. What remains is a smaller, cholesterol-rich particle: LDL. It carries most of the cholesterol in the blood. Source 1
8. LDL → Uptake into the cell LDL receptor Cells recognise ApoB-100 via the LDL receptor and internalise the whole particle. The cell itself regulates how many receptors sit on its surface; the protein PCSK9 breaks receptors down. Source 4
9. Uptake into the cell → HDL ABCA1, LCAT Cells pass surplus cholesterol via ABCA1 to the carrier protein ApoA-I. The enzyme LCAT esterifies it; a flat disc thus becomes a spherical HDL particle. Source 5
10. HDL → Back to the liver SR-B1 The liver takes up cholesterol from HDL via the receptor SR-B1. The enzyme CYP7A1 converts part of it into bile acids, which return to the gut with the bile. Source 5, 6

Cofactors in this pathway

• NADPH — Electron donor for HMG-CoA reductase and the later steps of the squalene pathway Source 2
• Coenzyme A — Carrier of the acetyl units from which HMG-CoA is assembled Source 1, 2
• Iron — Haem iron in the enzyme CYP51, which converts lanosterol on the way to cholesterol Source 8In the ORY catalogue as a laboratory value: Eisen
• Taurine — Attached in the liver to bile acids formed from cholesterol Source 6In the ORY catalogue as a laboratory value: Taurin
• Glycine — Second partner to which the liver attaches bile acids formed from cholesterol Source 6In the ORY catalogue as a laboratory value: Glycin

What acts on this pathway

• Statins — Statins inhibit HMG-CoA reductase. The liver cell then places more LDL receptors on its surface and removes more LDL from the blood; this mechanism is described pharmacologically. Source 7

Sources

1. Feingold KR. Introduction to Lipids and Lipoproteins. Endotext 2024 · PubMed 26247089
2. Sharpe LJ, Brown AJ. Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J Biol Chem 2013 · PubMed 23696639
3. Wang DQ. Regulation of intestinal cholesterol absorption. Annu Rev Physiol 2007 · PubMed 17002594
4. Jeon H, Blacklow SC. Structure and physiologic function of the low-density lipoprotein receptor. Annu Rev Biochem 2005 · PubMed 15952897
5. Sacher S, Mukherjee A, Ray A. Deciphering structural aspects of reverse cholesterol transport: mapping the knowns and unknowns. Biol Rev Camb Philos Soc 2023 · PubMed 36880422
6. Chiang JY. Bile acid metabolism and signaling. Compr Physiol 2013 · PubMed 23897684
7. Sirtori CR. The pharmacology of statins. Pharmacol Res 2014 · PubMed 24657242
8. Lepesheva GI, Waterman MR. Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms. Biochim Biophys Acta 2007 · PubMed 16963187

Whole pathway: Cholesterol and lipoproteins

Related pathways

• Cortisol — cholesterol
• DHEA — cholesterol
• Estradiol — cholesterol
• Bile acids — cholesterol
• Progesterone — cholesterol

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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