[The biosynthesis of glutathione in human erythrocytes (author's transl)].
The concentrations of glutathione precursors in human erythrocytes were investigated. 300muM glutamate, 375 muM glycine, and 10muM cysteine were found by automated amino acid analysis. The concentration of 2-aminobutyrate, the precursor of ophthalmic acid, was 15muM. The influence of the activities of endogenous or added glutamyl-cysteine synthetase and glutathione synthetase on the rate of glutathione biosynthesis was measured in membrane-free hemolysates under physiological conditions. The results show that the rate of the overall biosynthesis mainly depends on the formation of the dipeptide glutamyl-cysteine. The effect of glutathione precursor concentrations on the synthesis of the tripeptide was investigated at constant (endogenous) activities of the synthesizing enzymes. The rate was not enhanced by addition of glutamate and/or glycine unless cysteine or glutamyl-cysteine was also added. It is concluded that the concentration of cysteine limits the actual rate of the glutamyl-cysteine-synthetase reaction in vivo. No cysteine or bis(glutamyl)cystine was detected in human hemolysate; however, these disulfides were converted to glutathione. This indicates that erythrocytes have an appropriate system for their reduction, since the disulfides themselves are not substrates for the glutathione-synthesizing enzymes. Studies with intact human red cells indicate that the uptake of cysteine is the rate-determining step in the biosynthesis of glutathione.
D000596:Amino Acids / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis* / Q000097:blood; D005981:Glutathione Synthase / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D013997:Time Factors
D000596:Amino Acids; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione
Glutathionbiosynthese, VII[1-3] Die biosynthese von Glutathion in Humanerythrozyten