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Biomedical subjects

C Monder

Publications and source records attributed to C Monder.

At least 109 records · Page 6Linked to original sources

Studies in the biotransformation of cortisol to cortoic acids in man. III. 21-Oxidation of 4-14C,21-3H-desoxycorticosterone.

The metabolism of (4-14C, 21-3H) desoxycorticosterone (DOC) in man has been studied. DOC, like cortisol, undergoes oxidation at C-21 with the formation of acidic metabolites (2.3-8.2% of the dose). The release of 3H into the body water, either by oxidation or exchange, is approximately twice as great as the actual formation of acidic metabolites (as judged from the recovery of 14C in the urinary acidic fraction), but both parameters were considerably smaller than the corresponding values for cortisol. The principal metabolite isolated from the urine was 21-hydroxypregnanolone, which had an isotope ratio (3H/14C) greater than that of the dose; the pregnanetriols, which were formed in lesser amounts, had significantly lower isotope ratios than the dose. The absence of the 17-hydroxy group in DOC appears to modify C-21 oxidation, decreasing its magnitude and altering the character of the products.

Biotransformation↗

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).

Adrenal Cortex Hormones↗

17-Deoxygenation: a new pathway of cortisol metabolism. Isolation of 17-deoxycortolonic acids.

The existence of a 17-deoxylation pathway in the metabolism of cortisol has been established by isolation of two 17-deoxy metabolites of cortisol. They have been identified as the 20alpha and 20beta-hydroxy isomers of 3alpha,20-dihydroxy, 11-oxo-5beta-pregnan-21-oic acids by comparison of the nuclear magnetic resonance spectra (nmr) and high resolution mass spectra of their methyl esters with authentic samples and confirmed by reverse isotope dilution.

Humans↗

Spontaneous development of gluconeogenesis in fetal rat livers during incubation in organ culture.

Freshly isolated fetal liver explants in organ culture did not convert L-[14C]alanine or L-[14C]lactate to carbohydrate, but L-[14C]serine and D-[14C]glycerol were both transformed. When explants were subjected to 42 hr of preliminary incubation without supplements, followed by transfer to fresh medium with added precursor, all four substrates underwent gluconeogenic transformation. It was concluded that the ability of fetal rat liver in organ culture to convert alanine and lactate to carbohydrate evolves slowly, but the conversion of glycerol, and to a lesser extent serine, to glucose and glycogen is initiated immediately.

Alanine↗

The stereospecificity of the enzymic reduction of 21-dehydrocortisol by NADH.

(21R)-[21-3H]cortisol and (21S)-[21-3H]cortisol were synthesized by reduction of 21-dehydrocortisol by NADH in the presence of 21-hydroxysteroid dehydrogenase. The stereochemistry at carbon 21 was established after cleaving the side chain and oxidizing the resulting two epimers of tritiated glycolate with glycolate oxidase of known (2-pro-S) stereospecificity. From the distribution of radioactivity in the water and glyoxylate produced in this reaction, it was concluded that the reaction of 21-dehydrocortisol with (4S)-[4-3H]NADH catalyzed by 21-hydroxysteroid dehydrogenase results in a transfer of tritium from the 4S position of the nucleotide to form (21S)-[21-3H]cortisol, and that (21R)-[21-3H]cortisol resulted from the enzyme-catalyzed reduction of 21-dehydro[21-3H]cortisol with NADH. Nuclear magnetic resonance studies on both epimers at position 21 of [21-2H]cortisol and of [21-2H]cortisone prepared enzymically identify the transferring 21-pro-S hydrogen as the relatively downfield of the two 21-hydrogen atoms.

Deuterium↗