Cholesterols metabolism

The key importance of cholesterol (74) in animal systems has long been recognised. It is now becoming clear that this steroid may play an equally important role in plant systems although it can rarely be isolated. The incorporation of ) -sitosterol (86 = Et) into progesterone shows that the 24-alkyl group does not prevent 

The important insect hormone ecdysterone (122) and its precursor ponasterone A (123) also occur in a number of higher plants. As expected, both mevalonic 

While many mechanisms regnlate cholesterol homeostasis within the body, limited means of cholesterol input and ontpnt exist. Cholesterol input into the body pool is 

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Evans, A.J. Hood, R.L. Oakenfull, D.G. Sidhu, G.S. (1992). Relationship between structure and function of dietary fibre a comparative study of the effects of three galactomannans on cholesterol metabolism in the rat. British Journal of Nutrition, Vol.68, No.l, (July 1992), pp. 217-229, ISSN 0007-1145. 

HDL TAKES PART IN BOTH LIPOPROTEIN TRIACYLGLYCEROL CHOLESTEROL METABOLISM... 

Cross, C.E., Forte, T., Stocker, R., Louie, S., Yamamoto, Y., Ames, B.N. and Frei, B. (1990). Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. J. Lab. Clin. Med. 115, 396-404. 

Increased cholesterol concentrations have been associated with AD. The cholesterol increases P-amyloid protein synthesis which can lead to plaque formation.16 Also, the apo E4 allele is thought to be involved in cholesterol metabolism and is associated with higher cholesterol levels.16... 

Lakkaraju, A, Finnemann, SC, and Rodriguez-Boulan, E, 2007. The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells. I1 roc Nall Acad Sci USA 104, 11026-11031. 

The liver plays a decisive role in the cholesterol metabolism. The liver accounts for 90% of the overall endogenic cholesterol and its esters the liver is also impli-cated in the biliary secretion of cholesterol and in the distribution of cholesterol among other organs, since the liver is responsible for the synthesis of apoproteins for pre-p-lipoproteins, a-lipoproteins, and P-lipoproteins which transport the secreted cholesterol in the blood. In part, cholesterol is decomposed by intestinal micro-flora however, its major part is reduced to coprostanol and cholestanol which, together with a small amount of nonconverted cholesterol, are excreted in the feces. 

Brown MS, Goldstein JL. The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997 89 331-340. 

Fernandez LM, Lin ECK, Trejo A and McNamara DJ. 1994. Prickly pear (Opuntia sp.) pectin alters hepatic cholesterol metabolism without affecting cholesterol absorption in guinea pigs fed a hypercholesterolemic diet. J Nutt 124 817-824. 

This assay has been used by some authors to evaluate the in vitro effects of antioxidant extracts on LDL oxidation (Viana and others 1996 Cirico and Omaye 2006 Kedage and others 2007 Vayalil 2002 Garcfa-Alonso and others 2004 Tarwadi and Agte 2005). Oboh and others (2007) confirmed that hot pepper prevents in vitro lipid peroxidation in brain tissues. Indeed, Bub and others (2000) demonstrated that a moderate intervention with vegetable products rich in carotenoids reduces lipid peroxidation in men. Nicolle and others (2003) evaluated the effect of carrot intake on antioxidant status in cholesterol-fed rats. Later on, they showed that lettuce consumption improves cholesterol metabolism and antioxidant status in rats (Nicole and others 2004). 

Bobek P, Ozdin L and Hromadova M. 1998. The effect of dried tomato, grape and apple pomace on the cholesterol metabolism and antioxidative enzymatic system in rats with hypercholesterolemia. Nahrung 42(5) 317— 320. 

Nicolle C, Cardinault N, Aprikian O, Busserolles J, Grolier P, Rock E, Demigne C, Mazur A, Scalbert A, Amouroux P and Remesy C. 2003. Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat. Eur J Nutr 42(5) 254-261. 

Dietschy, J. M. and Turley, S. D. Thematic review series brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. /. Lipid Res. 45 1375-1397,2004. 

Cutler, R. G., Kelly, J., Storie, K. et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer s disease. Proc. Natl Acad. Sci. U.S.A. 101 2070-2075,2004. 

Lp(a) binds to the LDL receptor on cultured fibroblasts, although with a lower affinity than LDL itself. Once bound, Lp(a) inhibits 3HMG-CoA reductase, indicating that it is taken up by the cells and by releasing its cholesterol moiety, regulates the de novo synthesis of cholesterol (FI 2). High plasma concentrations of Lp(a) can, by this mechanism, influence cholesterol metabolism. As the LDL/Lp(a) ratio in plasma is about 50-100/1, this influence is marginal. 

Lp(a) can associate with LDL particles (Y3) and, as such, alter the intake of LDL by the apo-B E receptor pathway, thus indirectly influencing LDL and cholesterol metabolism. 

A high plasma concentration of LDL (usually measured as LDL-cholesterol) is a risk factor for the development of atheroma whereas a high concentration of HDL is an anti-risk factor for cardiovascular disease (CVD). Fundamental discoveries relating to cholesterol metabolism and the importance of the LDL receptor made by Nobel laureates Joseph Goldstein and Michael Brown led to an understanding of the role of LDL in atherosclerosis. The impact of HDL in reducing CVD risk is often explained by the removal of excess cholesterol from tissues and its return to the liver, a process known as reverse cholesterol transport. However, evidence from research by Gillian Cockerill and others shows that HDL has a fundamental anti-inflammatory role to play in cardioprotection. 

Leng-Peschlow, E. (1993). Effect of fibre on key enzymes of cholesterol synthesis and degradation In "Workshop on the Mechanisms of Action of Dietary Fibre on Lipid and Cholesterol Metabolism." Published by the Commission of the European Communities, Luxembourg, pp. 99-101. 

Sugama S, Kimura A, Chen W, Kubota S, Sepma Y, et al. 2001. Frontal lobe dementia with abnormal cholesterol metabolism and heterozygous mutation in sterol 27-hydroxylase gene CYP27). J Inherit Metab Dis 24 379-392. 

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Skogsberg, J., Kannisto, K., Cassel, T. N., Hamsten, A., Eriksson, P., and Ehrenborg, E. (2003) Evidence that peroxisome prohferator-activated receptor delta influences cholesterol metabolism in men. Arterioscler. Thromb. Vase. Biol. 23, 637-643. 

B. Cholesterol metabolism in liver cell and cholesterol-lowering drugs... 

Cholesterol can be derived from two sources—food or endogenous synthesis from ace-tyl-CoA. A substantial percentage of endogenous cholesterol synthesis takes place in the liver. Some cholesterol is required for the synthesis of bile acids (see p. 314). In addition, it serves as a building block for cell membranes (see p. 216), or can be esterified with fatty acids and stored in lipid droplets. The rest is released together into the blood in the form of lipoprotein complexes (VLDLs) and supplies other tissues. The liver also contributes to the cholesterol metabolism by taking up from the blood and breaking down lipoproteins that contain cholesterol and cholesterol esters (HDLs, IDLs, LDLs see p.278). 

Another example in which literature results were reanalyzed in view of the PSSC concept concerns the development of ligands for the farnesoid X receptor. The farnesoid X receptor is a transcriptional sensor for bile acids, the primary products of cholesterol metabolism, and plays an important role in lipid homeostasis. The farnesoid X receptor was, until recently, an orphan receptor, which means that no specific ligands existed for this receptor. Selective ligands for this receptor have been found in natural product libraries described by Nicolaou et al. The group of Nicolaou developed solid phase synthesis methods to make combinatorial libraries based on a benzopyran core structure. " A 10,000-membered combinatorial library based on the benzopyran core structure was synthesized and screened for activity on the farnesoid X receptor. The first specific ligands for the... 

HIV human immunodeficiency virus HMG-CoA hydroxymethylglutaryl coenzyme A (liver enzyme important in cholesterol metabolism)... 

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