MetaCyc EC 1.1.1.270 -- 3β-hydroxysteroid 3-dehydrogenase

Parent Class: EC-Numbers1 -- Oxidoreductases1.1 -- Acting on the CH-OH group of donors1.1.1 -- With NAD(+) or NADP(+) as acceptor

Synonyms: 3-keto-steroid reductase, 3-KSR, HSD17B7 (gene name), ERG27 (gene name)

Systematic Name: 3β-hydroxysteroid:NADP+ 3-oxidoreductase

Unification Links: BRENDA:1.1.1.270, ENZYME:1.1.1.270, IUBMB-ExplorEnz:1.1.1.270

Reaction:
a 3β-hydroxysteroid + NADP+ ← a 3-oxosteroid + NADPH + H+

Unofficial Reactions:
zymostenol + NADP+ ← 5α-cholesta-8-en-3-one + NADPH + H+,
4α-methyl-5α-cholesta-8-en-3-ol + NADP+ ← 4α-methyl-5α-cholesta-8-en-3-one + NADPH + H+,
isoavenasterol + NADP+ ← isoavenastenone + NADPH + H+,
zymosterol + NADP+ ← zymosterone + NADPH + H+,
5α-cholesta-7,24-dien-3β-ol + NADP+ ← 5α-cholesta-7,24-dien-3-one + NADPH + H+,
31-norcycloartenol + NADP+ ← 31-norcycloartenone + NADPH + H+,
cycloeucalenol + NADP+ ← cycloeucalenone + NADPH + H+,
4α-methyl-5α-cholest-7-en-3β-ol + NADP+ ← 4α-methyl-5α-cholest-7-en-3-one + NADPH + H+,
31-norcycloartanol + NADP+ ← 31-norcycloartanone + NADPH + H+,
lathosterol + NADP+ ← lathosterone + NADPH + H+,
4α-methyl-zymosterol + NADP+ ← 3-dehydro-4-methylzymosterol + NADPH + H+,
avenasterol + NADP+ ← avenastenone + NADPH + H+

Summary:
The enzyme participates in the biosynthesis of zymosterol, an intermediate of cholesterol biosynthesis. It is part of a three enzyme system that removes methyl groups from the C-4 position of steroid molecules. The first enzyme, ( EC 1.14.18.9, 4α-methylsterol monooxygenase, in fungi and animals, EC 1.14.18.10, plant 4,4-dimethylsterol C-4α-methyl-monooxygenase and EC 1.14.18.11, plant 4α-monomethylsterol monooxygenase in plants, or xxxx in bacteria) catalyzes three successive oxidations of the methyl group, resulting in a carboxylate group; the second enzyme, EC 1.1.1.170, 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating), catalyzes an oxidative decarboxylation that results in hydrogenation of the 3β-hydroxy group at at the C-3 carbon to an oxo group; and the last enzyme, EC 1.1.1.270, 3β-hydroxysteroid 3-dehydrogenase, reduces the 3-oxo group back to a 3β-hydroxyl. The mammalian enzyme is bifunctional and also catalyses EC 1.1.1.62, 17β-estradiol 17-dehydrogenase [Marijanovic03].

Citations: [Swindell68, Billheimer81, Gachotte99]


References

Billheimer81: Billheimer JT, Alcorn M, Gaylor JL (1981). "Solubilization and partial purification of a microsomal 3-ketosteroid reductase of cholesterol biosynthesis." Arch Biochem Biophys 211(1);430-8. PMID: 6946726

Gachotte99: Gachotte D, Sen SE, Eckstein J, Barbuch R, Krieger M, Ray BD, Bard M (1999). "Characterization of the Saccharomyces cerevisiae ERG27 gene encoding the 3-keto reductase involved in C-4 sterol demethylation." Proc Natl Acad Sci U S A 96(22);12655-60. PMID: 10535978

Marijanovic03: Marijanovic Z, Laubner D, Moller G, Gege C, Husen B, Adamski J, Breitling R (2003). "Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis." Mol Endocrinol 17(9);1715-25. PMID: 12829805

Swindell68: Swindell AC, Gaylor JL (1968). "Investigation of the component reactions of oxidative sterol demethylation. Formation and metabolism of 3-ketosteroid intermediates." J Biol Chem 243(21);5546-55. PMID: 4387005


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 46(D1):D633-D639 2018
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