Cholesterol lowering

Some of the most effective cholesterol lowering drugs act by inhibiting the enzyme that catalyzes this reaction... 

The practical development of plant sterol drugs as cholesterol-lowering agents will depend both on structural features of the sterols themselves and on the form of the administered agent. For example, the unsaturated sterol sitosterol is poorly absorbed in the human intestine, whereas sitostanol, the saturated analog, is almost totally unabsorbable. In addition, there is evidence that plant sterols administered in a soluble, micellar form (see page 261 for a description of micelles) are more effective in blocking cholesterol absorption than plant sterols administered in a solid, crystalline form. 

Denke, M. A., 1995. Lack of efficacy of low-dose sitostanol therapy as an adjunct to a cholesterol-lowering diet in men widi moderate hypercholesterolemia. American Journal of Clinical Nutrition 61 392—396. 

Derivatives of lovastatin have been found to be even more potent in cholesterol-lowering trials. Synvinolin lowers serum cholesterol levels at much lower doses than lovastatin. 

The cholesterol-lowering agents called statins, such as simvastatin (Zocor) and pravastatin (Pravachol), are among the most widely prescribed drugs in the world. Identify the functional groups in both, and tell how the two substances differ. 

Many valuable compounds are aromatic in part, including steroids such as estrone and well-known pharmaceuticals such as the cholesterol-lowering drug alorvastatin, marketed as Lipitor. Benzene itself has been found to cause bone marrow depression and a consequent lowered white blood ceil count on prolonged exposure. Benzene should therefore be handled cautiously if used as a laboratory solvent. 

Cholesterol Treatment Trialists (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 366 1267-1278... 

A class of cholesterol lowering drugs that inhibit 3-hydroxy-3-methylglutary 1-CoA reductase, the rate-limiting enzyme step in cholesterol biosynthesis. 

Schmitz G, Langmann T (2006) Pharmacogenomics of cholesterol-lowering therapy. Vascul Pharmacol 44(2) 75-89... 

The primary care provider may initially seek to control the cholesterol level by encouraging therapeutic life changes (TLC). This includes a cholesterol-lowering diet (TLC diet), physical activity, quitting smoking (if applicable), and weight management. The TLC diet is a... 

The study concerns the desymmetrization of the prochiral dinitrile (16) with preferential formation of the (Ji)-17, which was known to be a chiral intermediate in the synthesis of the cholesterol-lowering therapeutic drug (18) (Lipitor, Sortis, Torvast, etc.) as shown in Scheme 2.3. 

The biocatalytic differentiation of enantiotopic nitrile groups in prochiral or meso substrates has been studied by several research groups. For instance, the nitrilase-catalyzed desymmetrization of 3-hydroxyglutaronitrile [92,93] followed by an esterification provided ethyl-(Jl)-4-cyano-3-hydroxybutyrate, a useful intermediate in the synthesis of cholesterol-lowering dmg statins (Figure 6.32) [94,95]. The hydrolysis of prochiral a,a-disubstituted malononitriles by a Rhodococcus strain expressing nitrile hydratase/amidase activity resulted in the formation of (R)-a,a-disubstituted malo-namic acids (Figure 6.33) [96]. 

Figure 10.44 RibA catalyzed sequential aldol additions yielding a key chiral building block for cholesterol-lowering drugs.

The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of LDL receptors by poly-and monounsaturated as compared with saturated fatty acids, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, saturated fatty acids cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles—tendencies that may be regarded as atherogenic. 

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

RIDGES L, SUNDERLAND R, MOERMAN K, MEYER B, ASTHEIMER L, HOWE P (2001) Cholesterol lowering benefits of soy and linseed enriched foods. Asia Pac J Clin Nutr. 10 204-11. 

Observational studies have suggested possible favourable effects of estrogen replacement therapy (ERT) on the risk of coronary heart disease in postmenopausal women. Since elevated plasma cholesterol has been identified as the primary risk factor for cardiovascular disease, investigations have focused on the inverse association between plasma cholesterol concentration and soy protein consumption. The cholesterol-lowering properties of soy have been demonstrated, and a good correlation has been found in... 

Therapeutic lifestyle changes should be the first approach tried in all patients (Table 9—7).3 An adequate trial of TLC should be employed in all patients, but pharmacotherapy should be instituted concurrently in higher-risk patients. This includes dietary restrictions of cholesterol and saturated fats as well as regular exercise and weight reduction. In addition, therapeutic options to enhance LDL cholesterol lowering such as consumption of plant stanols/sterols (which competitively inhibit incorporation of cholesterol into micelles) and dietary fiber should be encouraged. These therapeutic options collectively may reduce LDL cholesterol by 20% to 25%. 

NCEP ATP III identified metabolic syndrome as an important target for further reducing CHD risk. Treatment of metabolic syndrome starts with increased physical activity, weight reduction (which also enhances LDL cholesterol lowering and... 

Cholesterol lowering Cancer, immunosuppression Parkinson s disease Urinary tract infections Peptic ulcers Cancer... 

Nguyen, T. T. (1999). The cholesterol-lowering action of plant stand esters. J. Nutr. 129(12) 2109-2112. 

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