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Cholesterol Transport

Cholesterolum

For medical students2 min readUpdated 2026-10-10

Cholesterol has extremely low solubility in water, so its transport in the blood is carried out within specialized protein-lipid complexes called lipoproteins. Depending on the density of these particles, a distinction is made between the transport of endogenous cholesterol to tissues and the reverse transport of excess cholesterol back to the liver.

Total poolThe human body contains about 140 g of cholesterol.

LocalizationThe main storage depots are the nervous and muscle tissues, as well as the liver.

Normal rangeThe blood concentration in adults should not exceed 5.2 mmol/L (200 mg/dL).

Dietary intakeAbout 1 g is ingested with food daily, of which half is absorbed.

Forms in the Body

Cholesterol is present in tissues and plasma in two main forms:

Free (unesterified) cholesterol is a structural component of biological membranes. In plasma membranes, it is located in the outer leaflet, with a phospholipid-to-cholesterol ratio of approximately 1:1. The free form is also present on the surface of lipoprotein particles.
Cholesterol esters serve as the storage form. Cholesterol is stored as esters in cells that synthesize steroid hormones and is transported within the inner hydrophobic core of lipoproteins.

Direct Transport (from Liver to Tissues)

The transport of endogenous cholesterol is mediated by very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL).

The liver synthesizes the apoB-100 protein component and assembles nascent VLDL.
In the bloodstream, they acquire apolipoproteins E and CII from high-density lipoproteins (HDL), becoming mature particles.
Under the action of lipoprotein lipase on capillary endothelium (activated by apoC-II), VLDL lose triacylglycerols and are converted into intermediate-density lipoproteins (IDL).
Subsequently, they transition into LDL, which interact with receptors on peripheral tissues or the liver via the apoB-100 protein, delivering cholesterol to cells.

Reverse Transport (to the Liver)

Excess cholesterol from peripheral tissues must be removed. This task is performed by HDL, which are synthesized in the liver and small intestine as disc-shaped precursors. In their immature state, they are rich in phospholipids and contain apolipoproteins E, C-II, A-I, and A-II, but contain almost no cholesterol.

The process of cholesterol uptake and packaging occurs in several stages:

The cellular protein ABCA1 transfers cholesterol from the cell membrane to the HDL particle (contact is mediated by apoA-I or apoE).
The enzyme lecithin-cholesterol acyltransferase (LCAT) is activated on the surface of the HDL. Its activator is the apoA-I protein.
LCAT catalyzes the esterification reaction: a fatty acid is transferred from phosphatidylcholine to cholesterol, forming hydrophobic cholesterol esters.
The esters move into the core of the particle. As a result, HDL acquire a spherical shape, increase in size, and transform into HDL₃.

Next, HDL deliver cholesterol to the liver, where it is partially converted into bile acids and excreted in the feces.

Frequently asked questions

Which receptors mediate cellular uptake of LDL and how does this process occur?

Cellular uptake of LDL is mediated by specific LDL receptors via endocytosis.

The process unfolds as follows:

Cell receptors recognize apolipoproteins on the surface of LDL (specifically apoB-100 and apoE).
Following receptor-lipoprotein interaction, the complex undergoes endocytosis into the cell.
Genetic mutations in the receptor impair the ability to undergo endocytosis after binding LDL, leading to hypercholesterolemia.

By what pathways is cholesterol eliminated from the body?

The primary route of cholesterol elimination from the body is via the intestine with feces.

Excess cholesterol in the liver is eliminated through the following pathways:

As synthesized bile acids (~0.5 g per day).
In unchanged form (~0.5 g per day).

A total of 1.0–1.3 g/day is eliminated through the intestine, accounting for over 90% of all excreted cholesterol. This pathway is the main mechanism for maintaining steroid homeostasis. Only minor quantities are excreted via other routes.

What key enzyme regulates endogenous cholesterol synthesis in the liver?

Endogenous cholesterol synthesis is regulated by the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase).

Enzyme activity is regulated by the following mechanisms:

Activation occurs with increased insulin secretion (promoting enzyme dephosphorilation) and the action of phosphatases.
Inactivation is triggered by kinases (phosphorylation stimulated by glucagon), a decrease in glucose concentration during fasting, and excessive dietary cholesterol intake (allosteric inhibition).

Excess cholesterol suppresses the expression of HMG-CoA reductase via negative feedback.

Why does cholesterol circulate freely in the blood if it is insoluble in water?

In plasma, cholesterol does not exist in a free state; rather, it is packaged within the hydrophobic core of lipoprotein complexes, which ensure its solubility and transport.

What is the difference between free cholesterol and its esters?

Free cholesterol is a component of cell membranes and lipoprotein coats, whereas cholesterol esters represent the hydrophobic storage form found within cells and the inner core of lipoproteins.

Which foods are sources of cholesterol?

Cholesterol is found exclusively in animal products: meat, liver, brain, egg yolks, and cheese. Plant sterols are virtually unabsorbed in the intestine.

Go deeper

Mechanism of intestinal cholesterol absorption (the role of mixed micelles)
Synthesis and structure of apolipoproteins (apoB-100, apoA-I, apoE)
Action of lipoprotein lipase on vascular endothelium
Conversion of cholesterol into bile acids in the liver
Interaction of LDL with cellular receptors