0-Hydroxy-/3-methylglutaryl coenzyme synthase

Hydroxy-3-methylglutaryl coenzyme A synthase inhibition. Seed oil, administered intragastrically to rats at a dose of 2 mL/kg, was active k Hydrogen peroxide release inhibition. Seed oil, administered to rats at a concentration of 8% of diet, was active on macrophages. Capsaicin or curcumin enhanced the effect° h... 

S Omura, H Tomoda, H Kumagai, MD Greenspan, JB Yodkovitz, JS Chen, AW Albert, I Martin, S Mochales, RL Monaghan, JC Chabala, RE Schwartz, AA Pat-chett. Potent inhibitory effect of antibiotic 1233A on cholesterol biosynthesis which specifically blocks 3-hydroxy-3-methylglutaryl coenzyme A synthase. J Antibiot 40 1356-1357, 1987. 

H Tomoda, H Kumagai, H Tanaka, S Omura. F-244 specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A synthase. Biochim Biophys Acta 922 351-356, 1987. 

Casals N., Buesa C., Marrero P. F., Belles X. and Hegardt, F. G. (2001) 3-Hydroxy-3-methylglutaryl coenzyme A synthase-1 of Blattella germanica has structural and functional features of an active retrogene. Insect Biochem. Molec. Biol. 31, 425 433. 

Gil G., Brown M. S. and Goldstein J. L. (1986) Cytoplsamic 3-hydroxy-3-methylglutaryl coenzyme A synthase from the hamster. J. Biol. Chem. 261, 3717-3724. 

Mascaro, C., Ortiz, J.A., Ramos, M.M., Haro, D., and Hegardt, F.G. (2000). Sterol regulatory element binding protein-mediated effect of fluvastatin on cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase transcription. Arch Biochem Biophys 374 286-292. 

Montamant, P, Guilloton, M., Karst, F. and Delrot, S. (1995) Isolation and characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy-3-methylglutaryl-coenzyme A synthase. Gene, 167,197-201. 

Smith JR, Osborne TF, Brown MS, Goldstein JL, Gil G (1988) Multiple sterol regulatory elements in promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A synthase. J Biol Chem 263 18480-18487... 

Laurent, F., L.F. Wentzinger, T.J. Bach, and M.-A. Hartmaim Iirhibition of squalene synthase and squalene epoxidase in tobacco cells triggers an up-regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase Plant Physiol. 130 (2002) 334-346. 

Studies of the 2-oxetanones having inhibitory activity on 3-hydroxy-3-methylglutaryl coenzyme A synthase (94CPB512) and investigations designed to probe factors affecting the hydrolytic stability of antibodies related to the naturally occurring (+)-... 

Gil-Gomez, G, Ayte, J. Hegardt, G. (1993) Ewr. J. Biochem. 213, 773-779. The rat mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal regulation and tissue specificity. 

Fig. 8.12 Heterologous and endogenous pathways used for the produetion of the monoterpenes (-)-carvone and ( )-perillyl alcohol in E. coli. AtoB acetyl-CoA acetyl-transfeiasehydroxymethylglutaiyl-CoA synthase, HMGR 3-hydroxy-3-methylglutaryl-coenzyme A reduc-...

Morris AA, Lascelles CV, Olpin SE, Lake BD, Leonard JV, Quant PA. Hepatic mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase deficiency. Pediatr Res 1998 44 392-396. 

In the first step, acetate (as a coenzyme A thioester) plus malonate gives acetoacetate, just as for the fatty acids. The next step is a different kind of reaction. Another acetate unit (as malonate) is added via an aldol condensation, using a HMG-CoA synthase enzyme, to give 3-hydroxy-P-methylglutaryl coenzyme A (HMG-CoA). This is reduced by NADPH with a HMG-CoA reductase to mevalonic acid (MVA) in the ratedetermining step for the whole sequence of reactions that builds up the... 

Mevalonic acid itself is a product of acetate metabolism. Three molecules of acetate coenzyme A, produced by the citric acid cycle, are used to form mevalonic acid (Scheme 5.1). Two molecules undergo a Claisen condensation via acetyl-CoA-acetyltransferase enzyme [EC 2.3.1.9] to produce acetoacetyl-CoA, and a third is incorporated in a stereospecific aldol addition to the formation of p-hydroxy-p-methylglutaryl-CoA (HMG-CoA) by the aid of HMG-CoA synthase [EC 2.3.3.10]. The first Claisen reaction was found to involve formation of Cys-89 acetyl-5-enzyme reaction intermediate [9]. Then, Cys-378 residue on the active site of the enzyme activates a second molecule of acetyl-CoA to initiate the condensation reaction (Fig. 5.4) [11]. Similarly, in HMG-CoA synthases (S. aureus HMG-CoA synthase), Cysl 11/129 are the crucial residues of covalent attach to acetyl-CoA to produce acetyl-enzyme thioester with the subsequent loss of coenzyme A (Fig. 5.4). Glu79/95 residues are responsible for the enolization of acetyl-enzyme intermediate in order to react with acetoacetyl-CoA, which is bound to His233/264 residues [12]. 

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