Open AccessThe Stoichiometry of the Conversion of Cholesterol and Hydroxycholesterols to Pregnenolone (3β-Hydroxypregn-5-en-20-one) Catalysed by Adrenal Cytochrome P -450
Author(s) -
Mikio Shikita,
Peter F. Hall
Publication year - 1974
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.71.4.1441
Subject(s) - pregnenolone , chemistry , cleavage (geology) , cytochrome , cholesterol side chain cleavage enzyme , stoichiometry , cholesterol , stereochemistry , biochemistry , organic chemistry , steroid , cytochrome p450 , metabolism , enzyme , biology , hormone , paleontology , fracture (geology)
The stoichiometry of the side-chain cleavage of cholesterol (cholest-5-en-3β-ol), 20α-hydroxycholesterol (cholest-5-ene-3β,20α-diol), and 20α,22-dihydroxycholesterol (cholest-5-ene-3β,20α,22-triol) has been examined with respect to TPNH, oxygen and H+ . Side-chain cleavage of cholesterol can be described by the following equation:Cholesterol + 3TPNH + 3H+ + 3O2 → Pregnenolone (3β-hydroxypregn-5-ene-20-one) + isocapraldehyde + 3 TPN+ 4H2 OStoichiometry of 20 α-hydroxycholesterol is 2TPNH and 2O2 per mole of cleavage and with 20α, 22-dihydroxycholesterol the values are 1:1:1. In addition 1 mole of H+ is consumed per mole of TPNH oxidized in each of these reactions. These observations are in keeping with a mechanism previously proposed in the literature, namely:Cholesterol → 20α-OH-Cholesterol → 20α, 22-di-OH-Cholesterol → pregnenolone Discordant observations are reviewed and it is concluded that insufficient data are available to sustain objections to this pathway.