Cholesterol characterization

Cholesterol was isolated m the eighteenth century but its structure is so complex that Its correct constitution was not determined until 1932 and its stereochemistry not verified until 1955 Steroids are characterized by the tetracyclic ring system shown m Figure 26 9a As shown m Figure 26 9b cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C 3 a double bond at C 5 methyl groups at C 10 and C 13 and a C Hn side chain at C 17 Isoprene units may be discerned m var lous portions of the cholesterol molecule but the overall correspondence with the iso prene rule is far from perfect Indeed cholesterol has only 27 carbon atoms three too few for It to be classed as a tnterpene... 

Atherosclerosis is a degenerative disease which is characterized by cholesterol-containing thickening of arterial walls. Saturated fatty acids, high levels of cholesterol, elevated blood pressure, and elevated serum lipoprotein are well-knowm risk... 

Steroid (Section 26.11) Type of lipid present in both plants and animals characterized by a nucleus of four fused rings (three are six-membered, one is five-membered). Cholesterol is the most abundant steroid in animals. 

An increase in serum lipids is believed to contribute to or cause atherosclerosis, a disease characterized by deposits of fatty plaques on the inner walls of arteries. These deposits result in a narrowing of the lumen (inside diameter) of the artery and a decrease in blood supply to the area served by the artery. When these fatty deposits occur in the coronary arteries, the patient experiences coronary artery disease. Lowering blood cholesterol levels can arrest or reverse atherosclerosis in the vessels and can significantly decrease the incidence of heart disease. 

Cardiovascular disease (CVD) is characterized by the involvement of the heart and allied vascular system. High cholesterol, associated lipid abnormahties and high blood pressure are recognized as the major risk factors of CVD. There have been several animal experiments and clinical studies using rice bran and rice bran oil, which have demonstrated a hypocholesterolemic effect (Raghuram et al., 1989 Rukmini and Raghuram, 1991 Sugano and Tsuji, 1997). The mechanisms involved are briefly summarized. 

Mott GE, AW Brinkley, CL Mersinger (1980) Biochemical characterization of cholesterol-reducing Eubacterium. Appl Environ Microbiol 40 1017-1022. 

Patients with metabolic syndrome are twice as likely to develop type 2 diabetes and four times more likely to develop CHD.3,11 These individuals are usually insulin resistant, obese, have hypertension, are in a prothrombotic state, and have atherogenic dyslipidemia characterized by low HDL cholesterol and elevated triglycerides, and an increased proportion of their LDL particles are small and dense.3... 

Krieger, M, 1999. Charting the fate of the good cholesterol Identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 68, 523-558. 

Lipids are transported between membranes. As indicated above, lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis. Because lipids are insoluble in water, special mechanisms must exist for the inter- and intracellular transport of membrane lipids. Vesicular trafficking, cytoplasmic transfer-exchange proteins and direct transfer across membrane contacts can transport lipids from one membrane to another. The best understood of such mechanisms is vesicular transport, wherein the lipid molecules are sorted into membrane vesicles that bud out from the donor membrane and travel to and then fuse with the recipient membrane. The well characterized transport of plasma cholesterol into cells via receptor-mediated endocytosis is a useful model of this type of lipid transport. [9, 20]. A brain specific transporter for cholesterol has been identified (see Chapter 5). It is believed that transport of cholesterol from the endoplasmic reticulum to other membranes and of glycolipids from the Golgi bodies to the plasma membrane is mediated by similar mechanisms. The transport of phosphoglycerides is less clearly understood. Recent evidence suggests that net phospholipid movement between subcellular membranes may occur via specialized zones of apposition, as characterized for transfer of PtdSer between mitochondria and the endoplasmic reticulum [21]. 

The bulk of pinocytosis in the nervous system is mediated by clathrin-mediated endocytosis (CME) [55] and this is the best-characterized pathway. More detail about clathrin-mediated pathways will be given when receptor-mediated endocytosis and the synaptic vesicle cycle pathways are considered. Pinocytosis through CME is responsible for uptake of essential nutrients such as cholesterol bound to low density lipoprotein (LDL) and transferring, but also plays a role in regulating the levels of membrane pumps and channels in neurons. Finally, CME is critical for normal synaptic vesicle recycling. 

Extracellular ligands (hormones, neurotrophins, carrier protein, adhesion molecules, small molecules, etc.) will bind to specific transmembrane receptors. This binding of specific ligand induces the concentration of the receptor in coated pits and internalization via clathrin-coated vesicles. One of the best studied and characterized examples of RME is the internalization of cholesterol by mammalian cells [69]. In the nervous system, there are a plethora of different membrane receptors that bind extracellular molecules, including neurotrophins, hormones and other cell modulators, being the best studied examples. This type of clathrin-mediated endocytosis is an amazingly efficient process, capable of concentrating... 

Familial hypercholesterolemia is characterized by a selective elevation in plasma LDL and deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas). 

ATP III recognizes the metabolic syndrome as a secondary target of risk reduction after LDL-C has been addressed. This syndrome is characterized by abdominal obesity, atherogenic dyslipidemia (elevated triglycerides, small LDL particles, low HDL cholesterol), increased blood pressure, insulin resistance (with or without glucose intolerance), and prothrom-botic and proinflammatory states. If the metabolic syndrome is present, the patient is considered to have a CHD risk equivalent. 

Lundeen SG, Carver JM, McKean ML, Winneker RC (1997) Characterization of the ovariectomized rat model for the evaluation of estrogen effects on plasma cholesterol levels. Endocrinology 138 1552-1558... 

The physiologic sequelae of biotin deficiency are almost unexplored. Severe skin lesions, especially seborrheic dermatitis and Leiner s disease (Erythroderma desquamativum or exfoliative dermatitis), were increased in young infants bom of mothers on a restricted diet low in eggs, livers, and other biotin-rich foods. After biotin administration the lesions healed. There are claims that excess biotin produces a fatty liver characterized by heightened cholesterol content. Choline has no effect in the prevention of biotin-fatty livers (G2, M2). In mice with transplanted tumors, both the tumors and the blood levels of biotin are below normal (R8). More recent studies established a protection with avidin, the biotin-binding fraction of egg white, against tumor formation (K4). More data along these lines are still needed for confirmation. 

K. Nakai, S. Tazuma, T. Nishioka and K. Chayama, Inhibition of cholesterol crystallization under bilirubi deconjugation partial characterization of mechanism whereby infected bile accelerates pigment stone formation. Biochem. Biophys. Acta 1632 (2003) 48-54. 

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