Cholesterol in the Human Body

Scheme 1. Cholesterol in the human body endogeneous build up, exogeneous introduction, and pathological consequences.

Lipoproteins produced in the liver take one of two forms. Low-density lipoproteins (LDL) carry cholesterol directly to cells. Because this cholesterol serves a useful biological function, it is sometimes called good cholesterol. High-density lipoproteins (HDL), by contrast, bypass cells and remain in the blood stream. The cholesterol in HDL lipoproteins serves no useful function in the body and is often referred to as bad cholesterol. The role of cholesterol in the human body and dietary methods of maintaining the correct HDL LDL ratio in the blood has been the subject of some controversy and considerable educational programs in recent decades. 

Isoprene is a key intermediary in the synthesis of cholesterol in the human body. 

In the early 70s, in Japan, Drs Endo and Kuroda began studies to find chemical entities that would inhibit the activity of HMC CoA reductase and thus interfere with the synthesis of cholesterol in the human body. They investigated many microorganisms to find such inhibitors since they proposed that such organisms might produce inhibitors in order to combat attack on the mevalonic acid biosynthesis, which is prevalent in many organisms. 

Diseases. Liquid crystals have been impHcated in a number of disease conditions in the human body. A complex cholesterol—phosphoHpid—Hpoprotein Hquid crystal phase has been identified in the initiation and maintenance of atheromatous deposits on the aortic intima in dissected human and rabbit arteries (40). The paracrystalHne nature of this precursor to plaque buildup with the resultant loss of arterial elasticity... 

In the human body choline is needed for the synthesis of phospholipids in cell membranes, methyl metabolism, transmembrane signaling and lipid cholesterol transport and metabolism [169]. It is transported into mammalian cells by a high-affinity sodium-dependent transport system. Intracellular choline is metabolized to phosphorylcholine, the reaction being catalyzed by the enzyme choline... 

Estradiol, testosterone, and progesterone are the principal sex hormones from the estrogen, androgen, and progestin gronps, respectively. These hormones are synthesized in the human body starting with cholesterol. 

Cholesterol is a soft waxy substance that is a steroidal alcohol or sterol. It is the most abundant steroid in the human body and is a component of every cell. Cholesterol is essential to life and most animals and many plants contain this compound. Cholesterol biosynthesis occurs primarily in the liver, but it may be produced in other organs. A number of other substances are synthesized from cholesterol including vitamin D, steroid hormones (including the sex hormones), and bile salts. Cholesterol resides mainly in cell membranes. 

A very similar reaction is catalyzed by 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase), which functions in the formation of acetoacetate in the human body (Eq. 17-5, step c) and also in the catabolism of leucine (Fig. 24-18)182183 and in the synthesis of 3-hydroxy-3-methyIgIutaryI-CoA, the presursor of cholesterol (Eq. 17-5, step fr)183a... 

Oxysterols are defined as oxygenated derivatives of cholest-5-en-3(3-ol (cholesterol) (Figure 18.1) or precursors of CHOL that may be formed directly by autoxidation or by the action of a specific monooxygenase, or that may be secondary to enzymatic or nonenzymatic lipid peroxidation (Guardiola et al., 1996 Schroepfer, 2000 Bjorkhem and Diczfalusy, 2002). These OS may be formed in the human body by endogenous free-radical attack on CHOL or by enzymatic processes, mainly in the biosynthesis of bile acids and steroid hormones. In addition, OS may be formed exogenously by autoxidation of CHOL in foods. The nomenclature and abbreviations of OS are presented in Table 18.1. It should be emphasized at this point that the OS that occur in... 

It is known that apoE plays an important role in the distribution and metabolism of cholesterol and triglycerides within many organs and cell types in the human body (Mahley et al., 2006). The apoE polymorphism is unique to humans and has been... 

Archeological evidence shows that pahn oil has been consumed by humans for more than 5000 years (145). Its digestion and absorption rates in the human body are in excess of 97%, which is very similar to other common edible oils and fats. In many communities pahn oil is an important source of dietary energy and provides sufficient quantities of the essential fatty acid, linoleic acid (18 2, n-6) for normal healthy metabolic functions. Like all other edible oils of vegetable origin, palm oil is considered cholesterol free. 

Vitamin D is a fat soluble vitamin derived from cholesterol. In the human epidermis (skin), sunlight spontaneously oxidizes cholesterol to 7-dehydrocholesterol (Fig. 10.10a). The 7-dehydrocholesterol leaks into the blood where it isomerizes to cholecalciferol (vitamin D3, Fig. 10.10b and c). Cholecalciferol is enzymatically hydroxylated at C25 in the liver (25-cholecalciferol) and then passes to the kidney where another enzyme is activated by parathyroid hormone to hydroxylate it at Cl, forming calcitriol (Fig. lO.lOd). The kidney hydroxylase is sensitive to feedback inhibition. As the amount of calcitriol increases, it binds to the hydroxylase and alters the specificity of the kidney enzyme. Additional 25-cholecal-ciferol is hydroxylated to 24,25-dihydroxycholecalciferol (inactive calcitriol) instead of 1,25 dihydroxycholecalciferol (calcitriol). Other vitamin D derivatives that can be converted to calcitriol are obtained enzymatically from cholesterol in other vertebrates. The most common of these are vitamin D3 (lamisterol) and D2 (ergosterol) from cold-water fish such as cod, where their presence keeps membranes fluid at low body temperatures 10-20°C. 

Fig. 10.10 Calcitriol synthesis in the human body, (a) Numbering of the cholesterol carbon atoms at each end of the molecule and position of oxidation site, (b, c) Isomerization to cholecalciferol. (d) Calcitriol showing the hydroxylation site in the liver (top right) and kidney (bottom left) (Modified from Fig. 27-32 of Biochemistry. L. Stryer, 4th Ed. 1995. W.H. Freeman Co., New York)...

It is very difficult to replace fat in food due to the very important function it plays in the human body. Fat is a concentrated energy source, a vitamin source and medium, in addition to providing structural functions. Fat mimetics must meet high requirements. These products must have fat-like properties such as flavor and sfruc-ture, but low energy, small cholesterol contents, and the ability to substitute 90% of the fat from a diet. 

Squalene is a naturally occurring triterpene and the precursor of steroids [66]. Oxidation (via squalene monooxygenase) of one of the terminal double bonds of squalene yields 2,3-squalene oxide, which undergoes enzyme-catalyzed cyclization to afford lanosterol, which is then elaborated into cholesterol and other steroids. Humans cannot live without squalene, because squalene is regarded as an essential building block for the production of hormones and other important substances in the human body. Squalene in olive oil may contribute to the low cholesterol levels of individuals consuming Mediterranean-style diets [67]. 

Elimination of cholesterol from the human body takes place primarily by the fecal route as bile acids and neutral sterols, viz. cholesterol, coprosta-nol, and coprostanone. About one-third of cholesterol is normally catabo-lized by way of bile acids (11). As will be shown later, the amount of the latter depends on the body size, so that the weight correlates with the fecal bile acids, the average daily output of 250 mg corresponding to about 4 mg/ kg. The factors regulating hepatic bile acid production under normal conditions are, however, unknown in many respects. 

The most abundant steroid in the human body, and the most important, is cholesterol ... 

Isolated for the first time in 1775 from gallstones by the physician Benjamin Gottlob Friedrich Conradi (Jena, Germany), cholesterol occurs everywhere in the human body. With high levels especially in the brain, the spinal cord and the suprarenal glands, the total amount of cholesterol in an adult adds up to some 240 grams. Invertebrates, on the other hand, synthesise in addition 24-dehydro-cholesterol in considerable quantity. 

Steroids and bile acids. The third major class of lipids is steroids. The structure of steroids is based on the cyclopentanoperhydrophenanthrene moiety (see Figure 12.5). Steroids exist in free form or as a conjugate of various molecules such as fatty acids, sulfuric acid, glucorinic acids, sugars, and amino acids. The most abundant steroid in the human body is cholesterol, which serves as a membrane component. It also acts as a precursor for the synthesis of other steroid hormones. Other known members of the steroid family are bile acids they are also derivative of cholesterol. 

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