Metabolism cholesterol, and

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... 

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. 

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. 

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. 

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... 

PO025 Me Call, M. R., T. Mehta, C. W. Leathers, and D. M. Foster. Psyllium husk I. Effect on plasma lipoprotein, cholesterol metabolism, and artherosclerosis in African green monkeys. Amer J Clin Nutr 1992 56(2) 376-384. 

In addition to treatment with the statins, hypercholesterolemia is sometimes treated with the use of nonabsorbable anion-exchange resins like cholestyramine (5.13) and colestipol, which sequester bile acid in the intestine, excrete them, and thus increase their synthesis in the liver by a feedback mechanism. Increased bile acid synthesis increases cholesterol metabolism and also decreases LDL concentrations. Unfortunately, these resins interfere with the absorption of other fats and fat-soluble vitamins (A, D, E, and K). They... 

Pharmaceuticals. Lecithin and especially purified phosphatidylcholine can act as excipients in pharmaceutical (drug) formulation to enhance and control the Unavailability of the active component. Moreover, phosphatidylcholine can be utilized as a diedelic source, as it involved in the cholesterol metabolism and the metabolism of fats in the liver also, it can be utilized as a precursor of brain acetylcholine, as neurotransmiticr. 

Harwood, H.J., Jr., Chandler, C.E., Pellarin, L.D., Bangerter, F.W., Wilkins, R.W., Long, C.A., Cosgrove, P.G., Malinow, M.R., Marzetta, C.A., Pettini, J.L., Savoy, Y.E., and Mayne, J.T. 1993. Pharmacologic consequences of cholesterol absorption inhibition Alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin /Migogenin cellobioside (CP-88818 tiqueside). J. Lipid Res. 34, 377-395. 

The search for intestinal cholesterol transporters extended for many years, beginning with a debate about whether or not it was even a protein-facilitated process (4, 5). The pancreatic enzyme carboxyl ester lipase (CEL, also called cholesterol esterase) was believed to be important to this process (6,7) and several companies devoted considerable resources to the development and testing of compounds to inhibit CEL, with mixed results (8-10). These efforts were abandoned in the mid-1990s, however, after studies with gene-knockout mice demonstrated that the enzyme was important only for absorption of cholesteryl ester (11, 12), which is a minor component of dietary cholesterol and is present at very low levels in bile. Interestingly, CEL is also found in liver where it has been shown to affect HDL metabolism (13). Thus, it may ultimately play an important role in cholesterol metabolism and may yet prove to be a useful drug target for CVD treatment (Camarota and Howies, unpublished). 

Schroepfer, Jr., G.J. 2000. Oxysterols modulators of cholesterol metabolism and other processes. Physiol. Rev. 80, 361-554. 

Howard (1976) recommended the baboon as model in atherosclerosis research because of the similarity of cholesterol metabolism and composition of the lipoproteins to man. 

Other conditions previously mentioned in this chapter, such as cancer, immunocompetence and interferon production, antihistamine eflFects in colds, increased iron absorption, eflFects on cholesterol metabolism, and nitrosamine blocking, were studied at higher than RDA dosage levels. These many situations require additional research study to determine what the minimum levels are to attain the optimal health condition. 

Cholesterol metabolism and bile acid biosynthesis. At least seven cytochrome P-450 enzymes play critical roles in the conversion of acetate into sterols and bile acids. Key among these are CYP51A1, CYP7A1, CYP7B1, and CYP39A1. The roles of each of these enzymes are beyond the scope of this article, but some excellent reviews and texts are available on the topic. 

The area of HDL cholesterol metabolism and function holds considerable promise in atheroprotection. Novel HDL-directed therapeutic interventions mainly target LXR (liver X receptor), ABCA1, apoA-I, CEPT (cholesteryl ester transfer protein), and EL (endothelial lipase) [12, 16, 70], The contribution of pharmacogenomics in the development of such drugs has not only been proven to be important (Fig. 2) but been required by the international drug regulatory bodies. Representative examples are presented below. 

Liver X receptors (LXRs) are nuclear receptors involved in the regulation of lipid metabolism and inflammatory responses in the CNS [440], LXR agonists induce the transcriptional activity of LXR target genes, attenuating the imbalance of cholesterol metabolism and overactivation of microglia and astrocytes in inflammation [441],... 

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