Hydroxymethylglutaryl-CoA reductase (NADPH)

In enzymology, a hydroxymethylglutaryl-CoA reductase (NADPH) (EC 1.1.1.34) is an enzyme that catalyzes the chemical reaction

(R)-mevalonate + CoA + 2 NADP⁺ ${\displaystyle \rightleftharpoons }$ (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H⁺

The 3 substrates of this enzyme are (R)-mevalonate, CoA, and NADP⁺, whereas its 3 products are (S)-3-hydroxy-3-methylglutaryl-CoA, NADPH, and H+.

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: 2572–8. 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.