期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1978
卷号：75
期号：10
页码：4806-4809
DOI：10.1073/pnas.75.10.4806
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：gamma-Glutamyl transpeptidase, a membrane-bound enzyme, functions in the gamma-glutamyl cycle to catalyze utilization of glutathione. It has been postulated that the amino-acid-stimulated utilization of glutathione by gamma-glutamyl transpeptidase reflects an aspect of amino acid translocation. As one approach to the effective in vivo inhibition of this enzyme, the inhibition of the enzyme by L-serine in the presence of borate buffers [Revel, J.P. & Ball, E.G. (1959) J. Biol. Chem. 234, 577-582] was reinvestigated. Inhibition by L-serine, D-serine, and alpha-methyl-DL-serine in the presence of borate is competitive with respect to gamma-glutamyl substrate and such inhibition is parallel to the activity of transpeptidase toward L-gamma-glutamyl, D-gamma-glutamyl, and L-gamma-(alpha-methyl)glutamyl derivatives. L-Serine and borate effectively protect against inactivation of the enzyme by the gamma-glutamyl analogs, 6-diazo-5-oxonorleucine and azaserine, which bind to the gamma-glutamyl site of the enzyme. These studies, kinetic investigations, equilibrium dialysis experiments, and other data support the view that inhibition is produced by formation of serine-borate complex which binds at the gamma-glutamyl binding site of the light subunit of gamma-glutamyl transpeptidase. The data indicate that serine-borate complex is a transition state inhibitor of gamma-glutamyl transpeptidase.
