Cholesterols homeostasis

The primary transporter of cholesterol in the blood is low density Hpoprotein (LDL). Once transported intraceUularly, cholesterol homeostasis is controlled primarily by suppressing cholesterol synthesis through inhibition of P-hydroxy-P-methyl gluterate-coenzyme A (HMG—CoA) reductase, acyl CoA—acyl transferase (ACAT), and down-regulation of LDL receptors. An important dmg in the regulation of cholesterol metaboHsm is lovastatin, also known as mevinolin, MK-803, and Mevacor, which is an HMG—CoA reductase inhibitor (Table 5). 

CYP46 hydroxylates cholesterol at the 24-position, a reaction that appears to play a role for cholesterol homeostasis in the brain. 

Peschel, D. et al., Cnrcnmin indnees changes in expression of genes involved in cholesterol homeostasis, J. Nutr. Biochem., 18, 113, 2007. 

Brown, M. S. and Goldstein, J. L. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science, 232(4746) 34-47. 

Bile helps in the digestion and absorption of fats. Its constituent bile acids (BAs) have detergent properties, and some can be carcinogenic. BAs can act as signalling molecules, entering the nuclei and reacting with the nuclear receptors and this could enhance or reduce BA synthesis. In this way, they control their own levels as well as those of their precursor, cholesterol. This controls cholesterol homeostasis and BA and lipid synthesis. 

Effect of endocytosed cholesterol on cellular cholesterol homeostasis The chylomicron remnant-, IDL-, and LDL-derived cholesterol affects cellular cholesterol content in several ways (see Figure 18.20). First, HMG CoA reductase is inhibited by ttfi cholesterol, as a result of which, de novo cholesterol synthesis decreases. Second, synthesis of new LDL receptor protein is reduced by decreasing the expression of the LDL receptor gene, thus limiting further entry of LDL cholestrol into cells. [Note ... 

Pennings M, Meurs I, Ye D, Out R, Hoekstra M, van Berkel T, van Eck M (2006) Regulation of cholesterol homeostasis in macrophages and consequences for atherosclerotic lesion development. FEBS Lett 580(23) 5588-5596... 

Similarly, apolipoprotein E expression increases in neurotoxicity mediated by KA (Table 6.3) (Boschert et al., 1999). Apolipoprotein E is a major lipoprotein in the brain. It is involved in the transport, distribution, and other aspects of cholesterol homeostasis. Apolipoprotein E also plays a dominant role in the mobilization and redistribution of brain lipids in repair, growth, and maintenance of nerve cells (Mahley, 1988). The secretion of apolipoproteins E and D may be differentially regulated in cultured astrocytes. In cell culture systems this depends upon the extracellular lipid milieu (Patel et al., 1995). During neurotoxicity mediated by KA, apolipoprotein E levels increase moderately in astrocytes and apolipoprotein E mRNA increases very strongly in clusters of CA1 and CA3 pyramidal neurons. Based on hybridization in situ and immunohistochemical studies, expression of apolipoprotein E in neurons may be a part of a rescue program to counteract neurodegeneration mediated by KA (Boschert et al., 1999). 

Liu, Y., Peterson, D. A., and Schubert, D. (1998). Amyloid beta peptide alters intracellular vesicle trafficking and cholesterol homeostasis. Proc Natl Acad Sci USA 95, 13266—13271. 

Absorption of cholesterol in the small intestine contributes to maintaining whole-body cholesterol homeostasis, yet the mechanisms of absorption have not been completely defined. For many years it was believed that cholesterol, a normal component of cell membranes, simply diffused through the brush border membrane of enterocytes (Grundy, 1983 Westergaard and Dietschy, 1974). However, the discovery of specific transporters, receptors,... 

The apoproteins of HDL are secreted by the liver and intestine. Much of the lipid comes from the surface monolayers of chylomicrons and VLDL during lipolysis. HDL also acquire cholesterol from peripheral tissues in a pathway that protects the cholesterol homeostasis of cells. In this process, free cholesterol is transported from the cell membrane by a transporter protein, ABCA1, acquired by a small particle termed prebeta-1 HDL, and then esterified by lecithin cholesterol acyltransferase (LCAT), leading to the formation of larger HDL species. The cholesteryl esters are transferred to VLDL, IDL, LDL, and chylomicron remnants with the aid of cholesteryl ester transfer protein (CETP). Much of the cholesteryl ester thus transferred is ultimately delivered to the liver by endocytosis of the acceptor lipoproteins. HDL can also deliver cholesteryl esters directly to the liver via a docking receptor (scavenger receptor, SR-BI) that does not endocytose the lipoproteins. 

Bjorkhem, I. 2002. Do oxysterols control cholesterol homeostasis J. Clin. Invest. 110, 725-730. Bjorkhem, I., Diczfalusy, U. 2002. Oxysterols. Friends, foes, or just fellow passengers Arterio-scler. Thromb. Vase. Biol. 22, 734-742. 

Wolf, G. 1999. The role of oxysterols in cholesterol homeostasis. Nutr. Rev. 57, 196-198... 

What are SREBP and SCAP What role do they play in the regulation of cholesterol homeostasis ... 

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