The stoichiometry of the conversion of cholesterol and hydroxycholesterols to pregnenolone (3β hydroxypregn 5 en 20 one) catalysed by adrenal cytochrome P 450

Abstract

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 + 3TPN+4H2O. Stoichiometry of 20α 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.