[Does a modified gamma-glutamyl cycle exist in human erythrocytes (author's transl)].
The first step in the biosynthesis of glutathione is the formation of gamma-glutamyl-cysteine by the enzyme glutamyl-cysteine synthetase. Since this enzyme is not specific for cysteine, different gamma-glutamylamino acids may be formed in vivo which represent potential substrates for the enzymes gamma-glutamylcyclotransferase; in this way 5-oxo-L-proline and free amino acid are formed. We investigated in membrane-free hemolysate the competition between the biosynthesis of glutathione or ophthalmic acid and the degradation of gamma-glutamyl peptides by measuring the formation of 5-oxoproline. The endogenous rate of 5-oxoproline production was 0.13 muM/min. This increased to 2muM/min after addition of 2-aminobutyrate, and to 10muM/min after addition of glutamate and 2-aminobutyrate to hemolysate. Addition of cysteine resulted in an increased oxoproline production only under conditions where glutamyl-cysteine accumulated. In addition, it was shown that for glutamyl-2-aminobutyrate the degradation to 5-oxoproline is faster than the utilization for the tripeptide synthesis. This was not the case for glutamyl-cysteine. Since membrane-free hemolysate (which lacks gamma-glutamyltransferase) is able to produce 5-oxoproline starting from glutamate, it is concluded that this 5-oxoprolinent amino acid transport via a modified gamma-glutamyl cycle.
D000613:Aminobutyrates / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D011392:Proline / Q000378:metabolism; D005722:gamma-Glutamylcyclotransferase / Q000378:metabolism
D000613:Aminobutyrates; D005971:Glutamates; D011392:Proline; D005722:gamma-Glutamylcyclotransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
Zur Frage eines modifizierten gamma-Glutamylzyklus in Human-Erythrozyten