Sterols [local] are an amazingly diverse class of molecules with many different functions. What they share in common is a structure with three six-carbon rings and a single five-carbon ring.
Several positions have been labeled with their designated numbers so that you will be better able to interpret the resources below. For example, cholesterol has a 3-OH that is on the A ring. Sterol structures depicted in line drawings and Chime animations.
Sterols have essential biochemical roles as hormones, vitamins, agents to make membranes more fluid, as plant protectants and as bile salts, emulsifying agents for fat catabolism. Sterols also share a common biosynthetic pathway with the class of biomolecules known as isoprenoids or terpenes. This pathway, starting with Acetyl-CoA and including important intermediates such as HMG-CoA and isopentylpyrophosphate is shown in this review [local]
Cholesterol is essential in relatively large quantities in animals where it has a major role in helping keep membranes fluid. It does this by inserting into the membrane bilayer with the 3-OH facing the aqueous phase. The rigid cholesterol ring structure forces greater fluidity in the fatty acyl chains of the membrane phospholipids. Although our bodies can synthesize cholesterol, we also tend to consume it with our diet. This can lead to health problems [local] and be a major cause of mortality. Much research has focused on the inhibition of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase, a key component of the cholesterol/sterol biosynthetic pathway.
This enzyme is involved in the pathway which constructs the five-carbon isopentyl pryophosphate, from acetyl-CoA. Isopentyl pyrophosphate is the building block used to construct the broad category of molecules called terpenes or isoprenoids. The isoprenoid pathway in plants produces important molecules for photosynthesis such as the carotenoids and part of the chlorophyll molecule, as well as many of the molecules producing what we consider characteristic food flavors and aromas. In animals, the isoprenoid pathway produces cholesterol (essential for membrane fluidity), bile salts (essential for digestion) and steroid hormones. Excess production of cholesterol in humans is a serious health problem because it results in a clogging of the arteries termed 'atherosclerosis'. Regulation of cholesterol levels in the blood is complex. Normally about one-third of cholesterol is acquired in the diet, whereas two-thirds is produced by the body itself, mostly in the intestines and liver. Efforts to reduce the amount of cholesterol in the diet and thereby lower serum cholesterol may not be successful because the body can respond by increasing its cholesterol production. In order to effectively lower serum cholesterol, it is necessary to inhibit the cholesterol biosynthetic pathway. Scientists have found a number of drugs that act as competitive inhibitors of HMG-CoA reductase. The most commonly used are Lovastatin, Pravastatin and Simvastatin.
Lovastatin [local] was discovered as a naturally occurring product of a fungus. Lovastatin itself is not an inhibitor of HMG-CoA reductase. However, it is metabolized in the body to a different molecule with a structure which mimics HMG-CoA. One indication of the specificity of lovastatin binding to HMG-CoA reductase is the different effect seen in different species. Since the primary structure (amino acid sequence) of HMG-CoA reductase will be differ slightly between species, it should be expected that the inhibitory product of lovastatin will bind more effectively to the enzyme from some species than to the enzyme from other species. Because of these differences, lovastatin is effective at inhibiting the HMG-CoA reductase activity in humans as well as in dogs and rabbits, but does not inhibit the enzyme in mice and rats.
Cholesterol serves as a precursor for the bile salts [local] produced in the gall bladder. These are amphiphilic molecules that solubilize fats in the gut and help with the absorption of lipids in the diet.
Cholesterol also serves as a precursor for steroid hormones and bile acids. It has recently been found that cholesterol is involved in providing signals for proper development of the fetus; defects in cholesterol metabolism and trafficking can result in birth defects producing one-eyed cyclops--usually fatal. See Evelyn Strauss (1998) Science 280:1528 "One-eyed animals implicate cholesterol in development".
Steroid hormones have a profound effect on development of the body. You may get the impression that they are safe to experiment with, to help shape the body. You may want to be a sports hero by taking androstenedione. There is a plethora of sites on the internet that say steroid precursors like androstenedione are wonderful, safe, and offer to sell some to you. It is more difficult to find reputable sites that offer objective information or would be appropriate for students [local].
Just remember, androstenedione is found in high concentrations in pregnant hyenas. Does it cause problems? Hyena placenta contains an enzyme called 17-beta-hydroxysteriod dehydrogenase (see metabolic map [local]) that converts androstenedione to testosterone. Female hyenas are born with an abnormally developed clitoris that forms a psuedopenis and labia that form a false scrotum. Does it make the pups a little hostile? Well, they are normally born in pairs and one kills the other shortly after birth.
There is also a lot of interest in the possible medical consequences of environmental estrogens. One example is resveratrol in the skin of grapes that may mimic estrogens and provide health benefits.
Other important sterols derived from cholesterol include Vitamin D and the cortisone drugs. Vitamin D [local] is essential for proper blood clotting. This vitamin is unusual in that a photochemical step is involved in its biosynthesis. This vitamin is also important for the proper balance of calcium and phosphate [local] needed for production of solid bones. A second product derived from cholesterol is the hormone epinepherine [local]. This hormone is important in mobilizing energy reserves when an organism is threatened, but also gets turned on by the stress of modern life. Another derivative from cholesterol is cortisone [local] which is widely used in medical applications for skin and joint problems.
While plants may not have large amounts of cholesterol, they do have their own sterols such as sitosterol, stigmasterol and campesterol. Compare the amount of sterol to other lipid components in olive oil [local]. Plants also produce sterols that have a protective function. Perhaps best known are the cardiac glycosides produced by plants such as foxglove (Digitalis) and Solonaceae, members of the deadly nightshade family. The molecule digitalis [local] started out as a folk medicine and is now a standard drug in the treatment of heart problems.
