Inhibition of a purified adrenal steroid 21-hydroxylating system by cytochrome P-450 particles

Biological Aspects of Cytochrome P450 and Associated Hydroxylation Reactions

“…The conversion of cholesterol and cholesterol sulphate to pregnenolone and pregnenolone sulphate, respectively, by bovine adrenocortical mitochondrial enzymes have been reported to proceed at about the same rate of 1,500-5,900 U/kg protein [159], The 17-and 21-hydroxylation activities of the adrenal cortex [124,142] appear to be located on the smooth-surfaced microsomes although certain mammalian steroid 21-hydroxylations may be cytochrome P450-independent [73,99]. It was found that the mitochondrial and micro somal cytochrome P450 concentration in the zona glomerulosa of the adrenal cortex was less than in the zona reticularis which in turn was less than in the zona fasciculata [67].…”

“…The schemes shown in figure 1 do not, however, take into account the possibility that certain adrenal microsomal 21-hydroxylations may be cyto chrome P450-independent [73,99]. It is unlikely that two alternative enzyme systems, one cytochrome P450-dependent and the other cytochrome P450-independent, for these 21-hydroxylation reactions exist in the same tissue, although the contradictory findings [24,73,99,124] relate principally to the 21-hydroxylation of 17a-hydroxyprogesterone.…”

“…It is unlikely that two alternative enzyme systems, one cytochrome P450-dependent and the other cytochrome P450-independent, for these 21-hydroxylation reactions exist in the same tissue, although the contradictory findings [24,73,99,124] relate principally to the 21-hydroxylation of 17a-hydroxyprogesterone. Such a hypothesis would need considerable additional experimental evidence for verification and would not readily help to clarify the biochemical basis of the genetic defect leading to the adrenogenital syndrome.…”