Glutathione dependent control of protein disulfide-sulfhydryl content by subcellular fractions of hepatic tissue.
The disulfide-sulfhydryl (SS/SH) ratios of subcellular fractions of rat hepatic tissue were found to vary diurnally with the ratio lowest in the early morning and highest in the early evening. These changes were found in the nuclear, microsomal and cytosol fractions. The primary reaction is the reversible formation of mixed disulfides of glutathione with proteins. This formation is controlled by the activity of thiol transferase and the level of oxidized glutathione (GSSG) as substrate. Several enzymes including mitochondrial and microsomal oxidases, glutathione reductase and peroxidase and glucose-6-phosphate dehydrogenase were found to control the levels of GSSG. An NADPH-dependent microsomal oxidase system, inhibited by GSSG, was found to produce activated oxygen which served as substrate for flutathione peroxidase. Evidence is presented for the concept that the formation of mixed disulfides of proteins with glutathione is a mechanism for maintenance of a disulfide-sulfhydryl ratio such that the integrity of particulate membranes is maintaine during oxidative and reductive stresses on the hepatic cells.
D000818:Animals; D002940:Circadian Rhythm; D004220:Disulfides / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004220:Disulfides; D011506:Proteins; D013438:Sulfhydryl Compounds; D010088:Oxidoreductases; D005954:Glucosephosphate Dehydrogenase; D010544:Peroxidases; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione