Cholesterol
is a member of a large group of substances called steroids,
which include vitamin D
and a number of steroid hormones,
among them the sex hormones of higher animals. In fact, cholesterol
is the precursor for the synthesis of many of these substances
and is also a precursor of the bile
acids.
Cholesterol is an important component of animal membranes and affects membrane fluidity. A space-filling model can be seen in Figure 10.9 and numbering of the ring system is shown in Figure 19.16. Cholesterol can be synthesized exclusively from acetyl-CoA (see here). An important regulatory enzyme in cholesterol biosynthesis is hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), which is allosterically inhibited in the presence of cholesterol. (See Cholesterol Biosynthesis)
A primary risk factor predisposing to heart disease is an abnormally elevated level of cholesterol in the blood. Prolonged cholesterol accumulation contributes to the development of atherosclerotic plaques, fatty deposits that line the inner surfaces of coronary arteries. Cholesterol is highly insoluble in the aqueous environment of blood, and it accumulates in white blood cells that become deposited at sites of injury or damage on inner arterial walls. If cholesterol levels are too high for its subsequent removal into the bloodstream, these cells become engorged with fatty deposits, which then harden into plaque, ultimately blocking key blood vessels and causing myocardial infarctions, or heart attacks.
Cholesterol travels in the bloodstream via lipoprotein complexes called Chylomicrons, VLDL, IDL, LDL, and HDL. Of the five lipoprotein classes, LDL is by far the richest in cholesterol. Cholesterol in plasma lipoproteins exists both as the free sterol and esterified at its hydroxyl position with a long-chain fatty acid, usually unsaturated (see also Table 18.1). The LDL particle contains a single molecule of apoprotein B-100 (Mr = 513,000) as its primary protein component. Because cholesterol biosynthesis is confined primarily to the liver with some occurring also in intestine, LDL plays an important role in delivering cholesterol to other tissues. Cholesterol esters are too hydrophobic to traverse cell membranes by themselves and must be transported into cells via specialized LDL receptors.
INTERNET LINK: