Biosynthesis of 18-oxocortisol by aldosterone-producing adrenal tissue.
Aldosterone-biosynthesizing adrenal tissue contains an angular methyl oxidase which converts corticosterone to 18-hydroxycorticosterone and aldosterone. Cortisol, when incubated with an active source of this oxidase, the bullfrog interrenal gland, was converted to 18-hydroxycortisol and a new C-18-oxygenated steroid identified as 11 beta, 17 alpha,21-trihydroxy-3,20-diketo-4-pregnene-18-al, or 18-oxocortisol. Proof of structure was based on the evidence that it was an alpha, beta-unsaturated ketone biosynthesized from cortisol with an empirical formula of C21H28O6. Low resolution gas chromatography-mass spectrometry of its fully derivatized methoxime trimethylsilyl ether confirmed a trioxopregnenetriol structure in which one aldehyde group was partially masked as an internal hemiacetal. That the oxo group had replaced the C-18 angular methyl was shown by oxidative degradation of the side chain with either periodic acid or sodium bismuthate to yield an hydroxy gamma-lactone rather than an etioacid. It is suggested that the corticosterone methyl oxidase system of aldosterone-producing cells has diminished substrate specificity enabling it to accept cortisol as a suboptimal substrate. Angular methyl oxidation of cortisol to its 18-hydroxy and 18-oxoderivative in two hypertensive disorders is attributed to a derangement in adrenocortical functional zonation permitting access of glucocorticoid products into the mineralocorticoid-biosynthesizing system.
D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D011892:Rana catesbeiana
C038135:18-oxocortisol; D000450:Aldosterone; D003345:Corticosterone; D006854:Hydrocortisone