Steroid 21 hydroxylase

Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.

As a mitochondrial P450 system, P450c11 is dependent on two electron transfer proteins, adrenodoxin reductase and adrenodoxin that transfer 2 electrons from NADPH to the P450 for each monooxygenase reaction catalyzed by the enzyme. In most respects this process of electron transfer appears similar to that of P450scc system that catalyzes cholesterol side chain cleavage. [9] Similar to P450scc the process of electrons transfer is leaky leading to superoxide production. The rate of electron leakage during metabolism depends on the functional groups of the steroid substrate. [10]

Dehydroepiandrosterone comes into subsequent oxidative transformation with production of 16Alpha-hydroxydehydroepiandrosterone . This oxidation is catalyzed by Cytochrome P450, family 3, subfamily A, polypeptide 7 ( CYP3A7) [10] , [11] , [12] and Cytochrome P450, family 3, subfamily A, polypeptide 4 ( CYP3A4) [13] , [10] , [11] . Oxidative metabolite of this reaction as well as Dehydroepiandrosterone can be further sulfated by steroid sulfatase (microsomal), isozyme S ( STS ) [14] , [15] , [16] , [15] , [14] . Dehydroepiandrosterone and Dehydroepiandrosterone sulfate can be transformed into other compounds with hormonal activity, Androstendiol and Androstendiol sulfate , respectively. These two reactions are catalyzed by Hydroxysteroid (17-beta) dehydrogenase 1 ( HSD17B1) [17] , [18] , [17] , [18] , Hydroxysteroid (17-beta) dehydrogenase 2 ( HSD17B2) [19] , [20] , [20] , [21] , and Hydroxysteroid (17-beta) dehydrogenase 7 ( HSD17B7 ) [22] , [23] , [23] , [24] .

Steroid 21 hydroxylase

steroid 21 hydroxylase

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