Hydrolysisof Glutathioneby Human Liver ‘y-Glutamyltransferase

We studied the catalytic hydrolysis of glutathione by human liver -y-glutamyltransferase [(y-glutamyl)-peptide:amino acid -y-glutamyltransferase, EC 2.3.2.21. Glutamate production from glutathione was maximal at pH 7.4 (37 #{176}C). Kinetically, the liver enzyme is similar to human kidney ‘y-glutamyltransferase: their respective Km values with glutathione as substrate are similar (0.096 X iO mol/L and 0.097 X iO mol/L, respectively). S-Methylglutathione was hydrolyzed at a slightly higher rate than glutathione by liver y-glutamyltransferase. From these findings and other established properties of liver and kidney yglutamyltransferase we propose that human liver is an important site of glutathione catabolism and that ‘y-glutamyltransferase in liver catalyzes the first step of the catabolism of glutathione and glutathione conjugates in this organ.