Accepted name: 4α-methylsterol monooxygenase
Reaction: 4,4-dimethyl-5α-cholest-7-en-3β-ol + 6 ferrocytochrome b5 + 3 O2 + 6 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 6 ferricytochrome b5 + 4 H2O (overall reaction)
(1a) 4,4-dimethyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 4α-hydroxymethyl-4β-methyl-5α-cholest-7-en-3β-ol + 2 ferricytochrome b5 + H2O
(1b) 4α-hydroxymethyl-4β-methyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferricytochrome b5 + 2 H2O
(1c) 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 2 ferricytochrome b5 + H2O
Other name(s): methylsterol hydroxylase (ambiguous); 4-methylsterol oxidase (ambiguous); 4,4-dimethyl-5α-cholest-7-en-3β-ol,hydrogen-donor:oxygen oxidoreductase (hydroxylating) (ambiguous); methylsterol monooxygenase (ambiguous); ERG25 (gene name); MSMO1 (gene name); 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b5:oxygen oxidoreductase (hydroxylating) (ambiguous)
Systematic name: 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b5:oxygen oxidoreductase (C4α-methyl-hydroxylating)
Comments: This enzyme is found in fungi and animals and catalyses a step in the biosynthesis of important sterol molecules such as ergosterol and cholesterol, respectively. The enzyme acts on the 4α-methyl group. Subsequent decarboxylation by EC, 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating), occurs concomitantly with epimerization of the remaining 4β-methyl into the 4α position, thus making it a suitable substrate for a second round of catalysis. cf. EC, 4β-methylsterol monooxygenase; EC, plant 4,4-dimethylsterol C-4α-methyl-monooxygenase; and EC, plant 4α-monomethylsterol monooxygenase.
1.  Miller, W.L., Kalafer, M.E., Gaylor, J.L. and Delwicke, C.V. Investigation of the component reactions of oxidative sterol demethylation. Study of the aerobic and anaerobic processes. Biochemistry 6 (1967) 2673–2678. [PMID: 4383278]
2.  Gaylor, J.L. and Mason, H.S. Investigation of the component reactions of oxidative sterol demethylation. Evidence against participation of cytochrome P-450. J. Biol. Chem. 243 (1968) 4966–4972. [PMID: 4234469]
3.  Sharpless, K.B., Snyder, T.E., Spencer, T.A., Maheshwari, K.K. and Nelson, J.A. Biological demethylation of 4,4-dimethyl sterols, Evidence for enzymic epimerization of the 4β-methyl group prior to its oxidative removal. J. Am. Chem. Soc. 91 (1969) 3394–3396. [PMID: 5791927]
4.  Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624–10629. [PMID: 7430141]
5.  Fukushima, H., Grinstead, G.F. and Gaylor, J.L. Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b5-dependence of 4-methyl sterol oxidase. J. Biol. Chem. 256 (1981) 4822–4826. [PMID: 7228857]
6.  Kawata, S., Trzaskos, J.M. and Gaylor, J.L. Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. J. Biol. Chem. 261 (1986) 3790–3799. [PMID: 3949790]
[EC created 1972 as EC, transferred 2002 to EC, transferred 2017 to EC, modified 2019]

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