Glutathione glutamyl transfer

The ability of enzyme preparations from various animal tissues to catalyze transfer of the glutamyl unit from glutamine or glutathione to certain a-amino acids and peptides, first observed by Hanes et al. (38), has been examined in several laboratories (32, 35, 39-41). Enzymes of this type have been studied recently by Orlowski and Meister (in hog kidney) (32) and by Szewczuk and Baranowski (in beef kidney) (41)-Results with the hog kidney enzyme will be reviewed here the beef enzyme is quite similar in many respects, but it is not identical in physical properties. 

GSH enables the transport of amino acids and low-molecular-weight peptides through cell membranes by transfer of y-L-glutamyl residues to amino acids and certain dipeptides [catalyzed by y-glutamyl transpeptidase (y-glutamyl transferase, abbreviation y-GT, EC 2.3.2,2)]. The detoxification of electrophilic xenobi-otic substances by elimination as - mostly water-soluble, non-toxic - 5-substituted acetylcysteine derivatives (so-called mercapturic acids) is initiated by glutathione S-transferases (abbreviation GST, EC 2.5.1.18). For further information on the biochemistry, see Lit.. ... 

Determination of y-GT y-GT is a glycoprotein and a membrane-bound enzyme that is located primarily on the outer surface of plasma membrane. y-GT plays a significant role in the glutathione metabolism and the transfer of the y-glutamyl moiety to certain amino acids that may be involved in the uptake of amino acids by a cell. The body s y-GT is present in order of decreasing activity in kidneys (relative activity 100), pancreas (24), and liver (7). The significant elevation of y-GT activity in serum is... 

The sulfur-containing amino acids, cysteine and methionine, are essential components of proteins and also participate in special reactions. In animals methionine is of particular importance because of its role in the transfer of methyl groups. Cysteine is a component of glutathione, 7-glutamyl-cysteinyl-glycine. The synthesis of these important amino acids occurs in plants and microorganisms by as yet undefined pathways. Certain interconversions at the amino acid level have been studied in animals, and some of the enzymes concerned have been identified. More is known about the degradation of the amino acids. 

One of the major points of interest in the chemistry of glutathione has been the chemistry of the mercaptan group. More recently, there has been an additional interest developed in the possibility of glutathione being a common intermediate in the synthesis of all peptide links, particularly in view of the existence of enzyme systems which transfer this 7-glutamyl residue to a whole variety of other amino acids. However, this is not the part of the subject to which I will be addressed. We will limit ourselves, then, to a discussion of sulfur chemistry. 

The enzyme for reaction (a) was shown not to be the same as that for the synthesis of glutamine from glutamic acid and ammonia. Neither did the purified enzymes for reactions (a) and (b) contain the enzyme that hydrolyzes glutathione. Therefore both transpeptidation and a transfer reaction analogous to 7-glutamyl transamidation are excluded from the mechanism of the synthesis of glutathione from its amino acids. 

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