title: Studies on the nature and regulation of the cellular thio:disulphide potential.
abstract: Microsomal fractions separated from homogenates of liver, kidney and corpora lutea contain a monooxygenase (dimethylaniline monooxygenase [N-oxide forming], EC 1.14.13.8) that catalyses NADPH- and oxygen-dependent oxidation of cysteamine to cystamine. The monooxygenase purified to homogeneity from hog liver also catalyses oxygenations of diverse xenobiotics, but it does not catalyse oxidation of any other physiological sulphur- or nitrogen-containing compounds. All the available evidence indicates that cysteamine is the physiological substrate for the monooxygenase, and the oxidation of this thiol to the disulphide may be a significant source of disulphide maintaining the cellular thiol:disulphide potential. The concentration of protein-low molecular weight mixed disulphide is a function of this potential. Changes in concentration of this protein-mixed disulphide reflect changes in thiol:disulphide balance. At constant substrate concentrations the potential would depend primarily on activity of the cytosol glutathione reductase (NAD(P)H: oxidized-glutathione oxidoreductase, EC 1.6.4.2) relative to that of the membrane-bound monooxygenase. In hepatic tissue from adult mice and hamsters there is a correlation between the concentration of protein-mixed disulphide and the activity of the monooxygenase relative to the reductase. Hepatic glutathione reductase is relatively constant in mice, but the monooxygenase is much higher in the female than in the male. After gonadectomy monooxygenase activity decreases in the female and increases in the male. Activities are restored to control levels by treating males with testosterone and females with progesterone. Testosterone decreases and progesterone increases activity. These two hormones apparently regulate the level of this enzyme in hepatic tissue.
mesh_terms: D000818:Animals; D002369:Castration; D006224:Cricetinae; D003543:Cysteamine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005980:Glutathione Reductase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D004220:Disulfides; D013438:Sulfhydryl Compounds; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D003543:Cysteamine; D005980:Glutathione Reductase