LDL-Cholesterin: the pathway in the body · Biomarker & Blood Analysis

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

Where this laboratory value sits: LDL — cholesterol-rich remnant. 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. How long it stays in the blood depends on the LDL receptors. Source 1

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. SREBP-2 regulates its synthesis in the liver.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

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. The location decides whether cholesterol or ketone bodies form. Source 2↑ supplies HMG-CoA is a junction: in the cytoplasm it leads to cholesterol, in the liver mitochondrion to ketone bodies. Which path is used depends on the location and the metabolic state. established physiology Source 2
   ⚖ When the balance tips

   too much — If HMG-CoA builds up because HMG-CoA reductase is slowed, less mevalonate forms; the cell signals this via SREBP-2 and makes more reductase and more LDL receptors.

   too little — If little HMG-CoA is available, the reductase gets less starting material, and the whole path to cholesterol runs more slowly.

   established physiology · Source 2, 7

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. When the cell holds little cholesterol, SREBP-2 switches this step up. Source 2↑ supplies Mevalonate is the building block for cholesterol and for other isoprenoids such as coenzyme Q10 and dolichol. When the sterol content of the cell falls, SREBP-2 switches up HMG-CoA reductase and the LDL receptor. established physiology Source 2, 7
   ⚖ When the balance tips

   too much — If there is plenty of sterol in the cell, HMG-CoA reductase is broken down faster and SREBP-2 is held back in the endoplasmic reticulum; less mevalonate then forms.

   too little — If little mevalonate is available, for instance when HMG-CoA reductase is inhibited, building material for cholesterol and other isoprenoids runs short; the liver cell then places more LDL receptors on its surface.

   established physiology · Source 2, 7

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. It makes cell membranes firmer and less permeable. Source 1, 2↑ supplies Cholesterol makes cell membranes firmer and less permeable and is the starting material for steroid hormones, vitamin D and bile acids. What the liver does not need itself, it esterifies or releases in VLDL. established physiology Source 1
   ⚖ When the balance tips

   too much — If free cholesterol builds up in the cell, it is esterified and stored in droplets; at the same time SREBP-2 slows the cell's own synthesis and the formation of new LDL receptors.

   too little — If there is little cholesterol in the cell, SREBP-2 becomes active: the cell makes more HMG-CoA reductase and more LDL receptors and so obtains cholesterol from its own synthesis and from the blood.

   established physiology · Source 2, 1

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. The balance of both determines how much cholesterol enters the body. Source 3↑ supplies NPC1L1 determines how much cholesterol passes from the gut lumen into the body. ABCG5 and ABCG8 act as counterparts and return cholesterol and plant sterols to the gut. established physiology Source 3
   ⚖ When the balance tips

   too much — If uptake via NPC1L1 outweighs return via ABCG5 and ABCG8, more cholesterol enters the chylomicrons and thus reaches the liver.

   too little — If NPC1L1 is slowed, more cholesterol stays in the gut and leaves the body; the liver partly offsets this through its own synthesis.

   established physiology · 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. In this way dietary cholesterol reaches the liver and slows its own synthesis there. Source 1↑ supplies Via the chylomicron remnants, dietary cholesterol reaches the liver. There it slows the liver's own synthesis via SREBP-2 and is passed on into VLDL or into the bile. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If remnants stay in the blood longer because the liver absorbs them more slowly, more cholesterol-rich particles circulate in the blood.

   too little — If few remnants reach the liver, less dietary cholesterol arrives there; the liver then makes more itself.

   established physiology · Source 1, 2

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. It supplies the tissues with fat between meals. Source 1↑ supplies VLDL supplies muscle and adipose tissue with triglycerides from the liver between meals. Once the fats are released, the particle gradually becomes cholesterol-rich LDL. established physiology Source 1
   ⚖ When the balance tips

   too much — If the liver releases more VLDL, more LDL also forms from it via lipoprotein lipase; more particles carrying ApoB-100 then circulate in the blood.

   too little — If the liver releases little VLDL, it retains more fat in its own cells; less LDL then forms in the blood.

   established physiology · 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. How long it stays in the blood depends on the LDL receptors. Source 1↑ supplies LDL distributes cholesterol to the cells of the body. How long an LDL particle stays in the blood depends mainly on how many LDL receptors remove it again. established physiology Source 1, 4
   ⚖ When the balance tips

   too much — If LDL builds up in the blood because few receptors absorb it, each particle circulates longer, and more cholesterol in the blood is bound in LDL.

   too little — If there is little LDL in the blood, the cells cover more of their needs from their own synthesis via HMG-CoA reductase.

   established physiology · Source 4, 2

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. Otherwise the receptor returns to the surface. Source 4↑ supplies The LDL receptor brings LDL into the cell; in the endosome the particle is released and the receptor returns to the surface. PCSK9 blocks this return and has the receptor broken down. established physiology Source 4
   ⚖ When the balance tips

   too much — If many LDL receptors sit on the surface, LDL is cleared from the blood quickly; the released cholesterol then slows the formation of new receptors via SREBP-2.

   too little — If few receptors sit on the surface, for instance because PCSK9 breaks many down, LDL stays in the blood longer, and the cell receives less cholesterol from outside.

   established physiology · Source 4, 2

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. In this way HDL withdraws cholesterol from cells. Source 5↓ depletes HDL withdraws surplus cholesterol from cells: ABCA1 passes it to ApoA-I, LCAT esterifies it and so holds it inside the particle. This is the start of the return transport to the liver. established physiology Source 5
   ⚖ When the balance tips

   too much — If a lot of HDL circulates, more acceptor sites for cholesterol from cells are available; how much actually returns to the liver also depends on LCAT and SR-B1.

   too little — If little ApoA-I is present or ABCA1 works slowly, few HDL particles form, and cells release surplus cholesterol less readily; it remains esterified inside the cell.

   established physiology · 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. By this route cholesterol leaves the body. Source 5, 6↑ supplies Through return transport and conversion into bile acids, cholesterol leaves the body. CYP7A1 is the slowest step here; bile acids returning to the liver slow it via the receptor FXR. established physiology Source 6, 5
    ⚖ When the balance tips

    too much — If a lot of cholesterol arrives in the liver, more of it is released into the bile, esterified or converted into bile acids; the liver's own synthesis is throttled at the same time.

    too little — If few bile acids return to the liver, for instance when they are bound in the gut, the liver switches up CYP7A1 and uses more cholesterol for new bile acids.

    established physiology · Source 6, 2

Further stations

• Acetyl-CoA — building block from breakdown The body makes most of its cholesterol itself, mainly in the liver. The starting material is acetyl-CoA, a fragment from the breakdown of sugar and fatty acids. The same building blocks also serve energy production. Source 1↑ supplies Acetyl-CoA supplies all the carbon atoms of cholesterol. The same building blocks also serve energy production and the synthesis of fatty acids; the cell divides them as needed. established physiology Source 2, 1
  ⚖ When the balance tips

  too much — If plenty of acetyl-CoA is present, more cholesterol does not form by itself: HMG-CoA reductase and SREBP-2 limit the pathway according to the sterol content of the cell.

  too little — If little acetyl-CoA is available, less building material is ready for the mevalonate pathway; the cell then covers more of its needs from LDL particles absorbed via the LDL receptor.

  established physiology · Source 2

• Cholesterol in the gut — from food and bile In the small intestine, cholesterol from food meets cholesterol from bile. The larger share comes from bile. What is not absorbed leaves the body with the stool. Source 3↑ supplies The cholesterol in the gut is mostly recycled bile cholesterol. Only part of it is absorbed; the rest leaves the body with the stool, one of the few routes by which the body releases cholesterol. established physiology Source 3, 6
  ⚖ When the balance tips

  too much — If a lot of dietary cholesterol arrives, the gut does not absorb unlimited amounts: ABCG5 and ABCG8 pump part of it back, and the liver throttles its own synthesis.

  too little — If little cholesterol arrives via the gut, the liver makes more itself; the cycle through the bile ensures that cholesterol is always present in the gut.

  established physiology · Source 3, 2

• Chylomicrons — dietary fat The gut cell packages fats and cholesterol into chylomicrons and releases them into the blood via the lymph. Their fats go to muscle and adipose tissue. Source 1↑ supplies Chylomicrons bring fat and cholesterol from food into the body. Their triglycerides go to muscle and adipose tissue; most of the cholesterol stays in the remnant and reaches the liver. established physiology Source 1
  ⚖ When the balance tips

  too much — If many chylomicrons enter the blood at once, lipoprotein lipase is busy for longer; the particles then remain in the blood longer until their fats are released.

  too little — If few chylomicrons form, less fat, cholesterol and fat-soluble vitamins from food reach the body.

  established physiology · Source 1

Cofactors in this pathway

• NADPH — Electron donor for HMG-CoA reductase and the later steps of the squalene pathway; without NADPH, synthesis stalls Source 2
• Coenzyme A — Carrier of the acetyl units from which HMG-CoA is assembled; starting point of the whole pathway Source 1, 2
• Iron — Haem iron in the enzyme CYP51, which converts lanosterol on the way to cholesterol; CYP51 needs haem iron Source 8In the ORY catalogue as a laboratory value: Eisen
• Taurine — Attached in the liver to bile acids formed from cholesterol; this makes them more water-soluble Source 6In the ORY catalogue as a laboratory value: Taurin
• Glycine — Second partner to which the liver attaches bile acids formed from cholesterol; this too makes them more water-soluble 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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