Oxidation of the 17-aldol (20 beta hydroxy-21-aldehyde) intermediate of corticosteroid metabolism to hydroxy acids by homogeneous human liver aldehyde dehydrogenases.
In human liver, the oxidation of corticosteroids to 20-hydroxy-21-oic acids proceeds via the formation and oxidation of aldol (20-hydroxy-21-aldehyde) intermediates. Human liver aldehyde dehydrogenases E1 and E2, which we have previously purified to homogeneity, catalyzed the oxidation of the aldol isomer of cortisol (isocortisol) or of 11-deoxycorticosterone (isoDOC) by E1 and E2 respectively, were identified by the criteria of chromatographic mobility, derivatization, and reverse isotope dilution of 4-14C labeled acid end products. Both enzymes showed broad substrate specificity and oxidized both 17-hydroxy and 17-deoxy steroids, though at widely varying rates. Kinetic analysis of the course of oxidation of isocortisol and isoDOC by NAD+ gave intersecting initial velocity plots that conform with a sequential mechanism. The inhibition patterns for both enzymes with thionicotinamide adenine dinucleotide or chloral hydrate were consistent with random sequential behavior.
D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D013379:Substrate Specificity
D000305:Adrenal Cortex Hormones; D007527:Isoenzymes; D009243:NAD; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase