Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Synthesis, Transport, and Excretion of Cholesterol
Cholesterol Transport — Tissue Cholesterol Balance

The factors influencing Cholesterol balance at THE TISSUE LEVEL are shown in Fig. 27.5.

An increase in tissue cholesterol content occurs through 1) the uptake of cholesterol-rich Lipoproteins by specific receptors, such as LDL receptors; 2) the receptor-independent uptake of cholesterol-containing lipoproteins; 3) the uptake of free cholesterol from cholesterol-rich lipoproteins directly by Cell membranes; 4) cholesterol synthesis; and 5) the Hydrolysis of cholesterol esters catalyzed by cholesterol ester hydrolase.

A decrease in cholesterol content is observed via 1) The transfer of cholesterol from membranes to lipoproteins with a low cholesterol content, particularly HDL₃ or newly formed HDL (this transfer is promoted by lecithin-cholesterol acyltransferase, LCAT); 2) the Esterification of cholesterol catalyzed by ACAT (acyl-CoA:cholesterol acyltransferase); and 3) the utilization of cholesterol for the Synthesis of Other Steroids, specifically Hormones or Bile acids in the Liver.

The LDL receptor (apo-B-100, E receptor)

In normal Cells, LDL receptors interact with the apo-B-100 Ligand on LDL particles, after which the intact LDL is internalized by receptor-mediated endocytosis. Inside Lysosomes, the LDL is degraded; its cholesterol esters are hydrolyzed, and free cholesterol is released into the Cytoplasm, where it inhibits HMG-CoA reductase and de novo cholesterol synthesis while activating ACAT. The number of LDL receptors on The Cell surface appears to be regulated According to the cell's demand for cholesterol required for membrane formation and steroid hormone Biosynthesis. As the intracellular cholesterol concentration increases, the number of LDL receptors decreases (Fig. 27.5).

The apo-B-100, E receptor is a high-affinity LDL receptor that is easily saturated under physiological conditions. Cell membranes also contain low-affinity LDL receptors.