3-Hydroxy-8-methylglutaryl CoA reductase

Starvation elicits mobilization of triglycerides from the adipose tissue and inhibits the endogenic cholesterol synthesis owing to the low activity of hydroxy-methylglutaryl-CoA reductase. The latter process provides the possibility for the active production of ketone bodies in the liver. 

ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxy-methylglutaryl-CoA reductase (NADPH)] phosphate (EC 1.1.1.34 hydroxy-methylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors.)... 

Ingebritsen, T.S. Parker, R.A. Gibson, D.M. Regulation of liver hydroxy-methylglutaryl-CoA reductase by a bicyclic phosphorylation system. J. Biol. Chem., 256, 1138-1144 (1981)... 

This effect may be due to the high level of PUFA, which is supported by evidence that com oil is more effective than olive oil in lowering LDL-cholesterol because com oil has higher PUFA (58.7 g/100 g oil) than olive oil (8.4 g/100 g oil) (Howell et al., 1998 Dupont et al., 1990). Com oil has a plant sterols content of 128 mg/lOOOkcal vs. 66 mg/lOOOkcal for olive oil, and these plant sterols can reduce cholesterol absorption from the gut which in turn lowers body pools and enhances synthesis rate through de-suppression of cellular hydroxy-methylglutaryl-CoA reductase activity (Howell et al., 1998 Maki, et al., 2015). This is supported by a recent human study that the hypocholesteremic effect of com oil is connected with the high amount of phytosterols (Wagner et al., 2001). 

Hampton, R. Y., R. G. Gardner, and J. Rine, Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Md Biol Cell, 1996, 7(12), 2029 4. 

This enzyme [EC 2.7.1.109], also known simply as reductase kinase, catalyzes the reaction of ATP with the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (NADPH) producing ADP and the phosphorylated form of the reductase. This phosphorylation inactivates the reductase. Histones can substitute for the reductase as substrates. 

Zapata R., D. Martin, M-D. Kulachs, and X. Belles (2002). Effects of h3fpocholesterolaemic agents on the expression and activity of 3-hydroxy-3-methylglutaryl-CoA reductase in the fat body of the German Cockroach. Archives of Insect Biochemistry and Physiology 49 177-186. 

Zapata R., M-D. Piulachs, and X. Belles (2(X)3). Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase lower fecundity in the German cockroach Correlation between the effects on fecundity in vivo with the inhibition of enzymatic activity in embryo cells. Pest Management Science 59 1111-1117. 

Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 1998 101 271 I -2719. 

Tabernero L., Bochar D. A., Rodwell V. W. and Stauffacher C. V. (1999) Substrate-induced closure of the flap domain in the ternary complex structures provides insights into the mechanism of catalysis by 3-hydroxy-3-methylglutaryl-CoA reductase. Proc. Natl. Acad. Sci. USA 96, 7167-7171. 

Kikuchi R, Kusuhara H, Abe T, et al. Involvement of multiple transporters in the efflux of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors across the blood-brain barrier. J Pharmacol Exp Ther 2004 311 1147-1153. 

HMG ((3-hydroxy-(3-methylglutaryl)-CoA reductase is a rate-limiting enzyme, which catalyzes the conversion of HMG-CoA to mevalonic acid. 

Which one of the following drugs decreases de novo cholesterol synthesis by inhibiting the enzyme 3-hydroxy-3-methylglutaryl CoA reductase ... 

J., Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral... 

Ohashi, K., Osuga, J., Tozawa, R., Kitamine, T., Yagyu, H., Sekiya, M., Tomita, S., Okazaki, H., Tamura, Y., Yahagi, N., lizuka, Y., Harada, K., et al. (2003). Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. J Biol Chem 278 42936 2941. 

Dale, S., Arro, M., Becerra, B., Morrice, N.G., Boronat, A., Hardie, D.G. and Ferrer A. (1995) Bacterial expression of the catalytic domain of 3-hydroxy-3-methylglutaryl-CoA reductase (isoform hmgrl) from Arabidopsis thaliana and its inactivation by phosphorylation at ser577 by Brassica oleracea 3-hydroxy-3-methylglutaryl-CoA reductase kinase. Bur.. Biochem., 233,506-13. 

Denbow, C.J., Lang, S. and Cramer, C.L. (1996) The N terminal domain of tomato 3-hydroxy-3-methylglutaryl-CoA reductases sequence, microsomal targeting and glycosylation. /. Biol. Chem., 271, 9710-5. 

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