Hydroxymethylglutaryl-CoA reductase (NADPH)

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hydroxymethylglutaryl-CoA reductase (NADPH)
HMG-CoA reductase tetramer, Human
EC no.
CAS no.9028-35-7
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

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

(R)-mevalonate + CoA + 2 NADP+ (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.


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[edit]

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.


  • 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.