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Proc Natl Acad Sci U S A. Apr 1974; 71(4): 1441–1445.
PMCID: PMC388245

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 + 3 TPN+ 4H2O

Stoichiometry 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.

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Selected References

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