3-Hydroxy-3-methyl-glutaryl CoA reductase

Isoprenoids or terpenoids are a large class of naturally occurring organic compounds with tremendous chemical and structural diversity. They are organic materials produced in the HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase pathway... 

Bok, S.H., Lee, S.H., Park, Y.B., Bae, K.H., Son, K.H., Jeong, T.S., and Choi, M.S., Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids, J. Nutr., 129, 1182, 1999. 

Elaborate cascades initiate the clotting of blood (Chapter 12) and the action of the protective complement system (Chapter 31). Cascades considered later in the book are involved in controlling transcription (Fig. 11-13) and in the regulation of mammalian pyruvate dehydrogenase (Eq. 17-9), 3-hydroxy-3-methyl-glutaryl-CoA reductase and eicosanoids (Chapter 21), and glutamine synthetase (Chapter 24). 

D. A. Kleinsek, R. E. Dugan, T. A. Baker, and J. W. Porter, 3-Hydroxy-3-methyl-glutaryl-CoA reductase from rat liver, Methods Enzymol. 1981, 73, 462-479. 

Pravastatin, a 3-hydroxy-3-methyl glutaryl CoA reductase inhibitor applied as a therapeutic agent for hypercholesterolemia, can be synthesized by stereo- and regioselective hydroxylation of compactin by the soil microorganism Streptomyces sp. Y-110 (Fig. 22) [152]. The fermentative production of pravastatin has already been applied on an industrial scale by Sankyo Co. using different Streptomyces bacteria strains [153, 154]. 

FIG. 1 Schematic diagram of cholesterol transport in the tissues, with sites of action of the main drug affecting lipoprotein metabolism (C = cholesterol CE = cholesteryl ester TG = triglycerides MV A = mevalonate HMG-CoA reductase = 3-hydroxy-3-methyl-glutaryl-CoA reductase YLDL = very low density lipoproteins LDL = low density lipoproteins HDL = high density lipoproteins). (Reprinted from Rang et al (1999), with permission from Elsevier Science.)... 

Mice were fed diets containing either 6% HL-SAF (normal), 4 HL-SAF + 2% CLA (lipodystrophy control), or 3.5% HL-SAF + 2% CLA + 0.5% DHA (lipodystrophy + DHA) for 4 weeks. Values are expressed as mean + standard error for six mice. Different letters show significant differences at p < 0.05. HMG, 3-hydroxy-3-methyl-glutaryl-CoA reductase, ACAT1, acyl-CoA cholesterol acyltransferase-1. 

Together with y-oryzanol, tocotrienols are responsible for the cholesterol-lowering effect of rice bran oil (250). Tocotrienol concentrates have been shown to have a hypocholesterolemic effect in animals and humans (251-257) possibly because of inhibition of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) (251, 258, 259). The presence of a-tocopherol at concentrations >20% in tocotrienol concentrates was, however, found to attenuate the inhibitory elfect of tocotrienols on HMG-COA reductase, thereby weakening their cholesterollowering activities (254). Tocotrienols were especially found to synergize the cholesterol-lowering effect of lovastatin (254). In addition, tocotrienols have been shown to influence certain hemostatic parameters and to reduce the occurrence of chemical-induced tumors in the rat (253). 

This may be accounted for by the fact that the activity of the key regulatory enzyme of sterol biosynthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase, is reduced in this yeast by C-14 methyl sterols such as lanosterol that accumulate in response to treatment with these inhibitors (44,45). 

Regulation of Liver 3-Hydroxy-3-methyl-glutaryl-CoA Reductase Zafarul H. Beg and H. Bryan Brewer, Jr. 

HMG-CoA. See 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) HMG-CoA reductase, 2678, 4115,4126,4130 HMGR. See 3-Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) Hemiterpenoids, 2720 H-NMR, 332, 916, 3476 Hodgkins lymphoma, 588 Holarrhena curtisii, 1289 Holoparasites, 3585 HOMA-IR. See Homeostasis model... 

---