formulas are shown in Figure 68-4. Phospholipids always contain one or more fatty acid molecules and one phosphoric acid radical, and they usually contain a nitrogenous base. Although the chemical structures of phospholipids are somewhat variant, their physical properties are similar because they are all lipid soluble, transported in lipoproteins, and used throughout the body for various structural purposes, such as in cell membranes and intracellular membranes.
Formation of Phospholipids. Phospholipids are synthesized in essentially all cells of the body, although certain cells have a special ability to form great quantities of them. Probably 90 per cent are formed in the liver cells; substantial quantities are also formed by the intestinal epithelial cells during lipid absorption from the gut.
The rate of phospholipid formation is governed to some extent by the usual factors that control the overall
Cholesterol, the formula of which is shown in Figure 68-5, is present in the diets of all people, and it can be absorbed slowly from the gastrointestinal tract into the intestinal lymph. It is highly fat soluble but only slightly soluble in water. It is specifically capable of forming esters with fatty acids. Indeed, about 70 per cent of the cholesterol in the lipoproteins of the plasma is in the form of cholesterol esters.
Formation of Cholesterol. Besides the cholesterol absorbed each day from the gastrointestinal tract, which is called exogenous cholesterol, an even greater quantity is formed in the cells of the body, called endogenous cholesterol. Essentially all the endogenous cholesterol that circulates in the lipoproteins of the plasma is formed by the liver, but all other cells of the body form at least some cholesterol, which is consistent with the fact that many of the membranous structures of all cells are partially composed of this substance.
The basic structure of cholesterol is a sterol nucleus. This is synthesized entirely from multiple molecules of acetyl-CoA. In turn, the sterol nucleus can be modified by means of various side chains to form (1) cholesterol; (2) cholic acid, which is the basis of the bile acids formed in the liver; and (3) many important steroid hormones secreted by the adrenal cortex, the ovaries, and the testes (these hormones are discussed in later chapters).
Factors That Affect Plasma Cholesterol Concentration—Feedback Control of Body Cholesterol. Among the important factors that affect plasma cholesterol concentration are the following:
1. An increase in the amount of cholesterol ingested each day increases the plasma concentration slightly. However, when cholesterol is ingested, the rising concentration of cholesterol inhibits the most essential enzyme for endogenous synthesis of cholesterol, 3-hydroxy-3-methylglutaryl CoA reductase, thus providing an intrinsic feedback control system to prevent an excessive increase in plasma cholesterol concentration. As a result, plasma cholesterol concentration usually is not changed upward or downward more than ±15 per cent by altering the amount of cholesterol in the diet, although the response of individuals differs markedly.
2. A highly saturated fat diet increases blood cholesterol concentration 15 to 25 per cent. This results from increased fat deposition in the liver, which then provides increased quantities of acetyl-CoA in the liver cells for the production of cholesterol. Therefore, to decrease the blood cholesterol concentration, it is usually just as important, if not more important, to maintain a diet low in saturated fat as to maintain a diet low in cholesterol.
3. Ingestion of fat containing highly unsaturated fatty acids usually depresses the blood cholesterol concentration a slight to moderate amount. The mechanism of this effect is unknown, despite the fact that this observation is the basis of much present-day dietary strategy.
4. Lack of insulin or thyroid hormone increases the blood cholesterol concentration, whereas excess thyroid hormone decreases the concentration. These effects are probably caused mainly by changes in the degree of activation of specific enzymes responsible for the metabolism of lipid substances.
Specific Uses of Cholesterol in the Body. By far the most abundant nonmembranous use of cholesterol in the body is to form cholic acid in the liver. As much as 80 per cent of cholesterol is converted into cholic acid. As explained in Chapter 70, this is conjugated with other substances to form bile salts, which promote digestion and absorption of fats.
A small quantity of cholesterol is used by (1) the adrenal glands to form adrenocortical hormones, (2) the ovaries to form progesterone and estrogen, and (3) the testes to form testosterone. These glands can also synthesize their own sterols and then form hormones from them, as discussed in the chapters on endocrinology.
A large amount of cholesterol is precipitated in the corneum of the skin. This, along with other lipids, makes the skin highly resistant to the absorption of water-soluble substances and to the action of many chemical agents, because cholesterol and the other skin lipids are highly inert to acids and to many solvents that might otherwise easily penetrate the body. Also, these lipid substances help prevent water evaporation from the skin; without this protection, the amount of evaporation can be 5 to 10 liters per day (as occurs in burn patients who have lost their skin) instead of the usual 300 to 400 milliliters.
Cellular Structural Functions of Phospholipids and Cholesterol— Especially for Membranes
The previously mentioned uses of phospholipids and cholesterol are of only minor importance in comparison with their function of forming specialized structures, mainly membranes, in all cells of the body. In Chapter 2, it was pointed out that large quantities of phospholipids and cholesterol are present in both the cell membrane and the membranes of the internal organelles of all cells. It is also known that the ratio of membrane cholesterol to phospholipids is especially important in determining the fluidity of the cell membranes.
For membranes to be formed, substances that are not soluble in water must be available. In general, the only substances in the body that are not soluble in water (besides the inorganic substances of bone) are the lipids and some proteins. Thus, the physical integrity of cells everywhere in the body is based mainly on phospho-lipids, cholesterol, and certain insoluble proteins. The polar charges on the phospholipids also reduce the interfacial tension between the cell membranes and the surrounding fluids.
Another fact that indicates the importance of phos-pholipids and cholesterol for the formation of structural elements of the cells is the slow turnover rates of these substances in most nonhepatic tissues—turnover rates measured in months or years. For instance, their function in brain cells to provide memory processes is related mainly to their indestructible physical properties.
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