Hydroxymethylglutaryl-CoA reductase (NADPH)

This enzyme belongs to the family of oxidoreductases, to be specific those acting on the CH-OH group of donor with NAD or NADP as acceptor. This enzyme participates in biosynthesis of steroids including cholesterol. The statin class of anticholesterol drugs act through inhibiting this enzyme.

Nomenclature

The systematic name of this enzyme class is (R)-mevalonate:NADP oxidoreductase (CoA-acylating). Other names in common use include:

hydroxymethylglutaryl coenzyme A reductase (reduced nicotinamide adenine dinucleotide phosphate)
3-hydroxy-3-methylglutaryl-CoA reductase
β-hydroxy-β-methylglutaryl coenzyme A reductase
hydroxymethylglutaryl CoA reductase (NADPH)
S-3-hydroxy-3-methylglutaryl-CoA reductase
NADPH-hydroxymethylglutaryl-CoA reductase
HMGCoA reductase-mevalonate:NADP-oxidoreductase (acetylating-CoA)
3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
hydroxymethylglutaryl-CoA reductase (NADPH₂).

Structural studies

As of late 2007, 12 structures have been solved for this class of enzymes, with PDB accession codes 1DQ8, 1DQ9, 1DQA, 1HW8, 1HW9, 1HWI, 1HWJ, 1HWK, 1HWL, 2Q1L, 2Q6B, and 2Q6C.

References

Bucher NL, Overath P, Lynen F (1960). "β-Hydroxy-β-methylglutaryl coenzyme A reductase, cleavage and condensing enzymes in relation to cholesterol formation in rat liver". Biochim. Biophys. Acta. 40: 491–501. doi:10.1016/0006-3002(60)91390-1. PMID 13805544.
Durr IF, Rudney H (1960). "The reduction of β-hydroxy-β-methyl-glutaryl coenzyme A to mevalonic acid". J. Biol. Chem. 235 (9): 2572–8. doi:10.1016/S0021-9258(19)76915-4. PMID 13818862.
Kawachi T, Rudney H (1970). "Solubilization and purification of β-hydroxy-β-methylglutaryl coenzyme A reductase from rat liver". Biochemistry. 9 (8): 1700–5. doi:10.1021/bi00810a008. PMID 4985697.

v t e Oxidoreductases: alcohol oxidoreductases (EC 1.1)
1.1.1: NAD/NADP acceptor	3-hydroxyacyl-CoA dehydrogenase 3-hydroxybutyryl-CoA dehydrogenase Alcohol dehydrogenase Aldo-keto reductase 1A1 1B1 1B10 1C1 1C3 1C4 7A2 Aldose reductase Beta-Ketoacyl ACP reductase Carbohydrate dehydrogenases Carnitine dehydrogenase D-malate dehydrogenase (decarboxylating) DXP reductoisomerase Glucose-6-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase HMG-CoA reductase IMP dehydrogenase Isocitrate dehydrogenase Lactate dehydrogenase L-threonine dehydrogenase L-xylulose reductase Malate dehydrogenase Malate dehydrogenase (decarboxylating) Malate dehydrogenase (NADP+) Malate dehydrogenase (oxaloacetate-decarboxylating) Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) Phosphogluconate dehydrogenase Sorbitol dehydrogenase Hydroxysteroid dehydrogenase: 3β 3β-HSD NSDHL 11β 11β-HSD1 11β-HSD2 17β
1.1.2: cytochrome acceptor	D-lactate dehydrogenase (cytochrome) D-lactate dehydrogenase (cytochrome c-553) Mannitol dehydrogenase (cytochrome)
1.1.3: oxygen acceptor	Glucose oxidase L-gulonolactone oxidase Xanthine oxidase Alcohol oxidase
1.1.4: disulfide as acceptor	Vitamin K epoxide reductase Vitamin-K-epoxide reductase (warfarin-insensitive)
1.1.5: quinone/similar acceptor	Malate dehydrogenase (quinone) Quinoprotein glucose dehydrogenase
1.1.99: other acceptors	Choline dehydrogenase L2HGDH

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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