Oxidation of corticosteroids to steroidal-21-oic acids by human liver enzyme.
An enzyme that oxidizes corticosteroids to acidic metabolites has been purified from postmortem human liver. The most rapidly oxidized substrate was 11-deoxycorticosterone (DOC). Other corticosteroids were oxidized at rates that were 10% or less of DOC. The products of DOC oxidation were 3, 20-dioxopregn-4-en-21-oic acid and 20-hydroxy-3-oxopregn-4-en-21-oic acid. The 20-keto acid was the predominant metabolite in all enzyme preparations. Keto acid and hydroxy acid were not interconverted. Enzyme activity was assayed by measuring the transfer of tritium from [21-3H]DOC to water. The enzyme is yellow, and has spectral maxima at 278 and 405 nm. Inhibition by o-phenanthroline suggests that it may be a metalloenzyme. Molecular weight was estimated at 74 000 +/- 8 000; a pH maximum occurred at pH 8-8.5. This enzyme may participate in the in vivo conversion of corticosteroids to the acidic metabolites that we have described previously (H.L. Bradlow et al. (1973), J. Clin. Endocrinol. Metab. 37, 811).
D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D002413:Cations, Divalent; D002414:Cations, Monovalent; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D000305:Adrenal Cortex Hormones; D002413:Cations, Divalent; D002414:Cations, Monovalent; D010088:Oxidoreductases