Biochemical regulation of the activity of gamma-glutamylcysteine synthetase from rat liver and kidney by glutathione.

Rat liver and kidney gamma-glutamylcysteine synthetase (gamma GCS) had similar catalytic properties and consisted of heavy and light subunits, but the molecular structure of the two enzymes was not the same as evidenced by the results of SDS-PAGE and disc gel electrophoresis. Unlike kidney enzyme, most of liver gamma GCS was in a reduced enzyme form which did not have disulfide linkage between heavy and light subunits. Although the oxidized form of the two enzymes which subunits were linked with disulfide bond(s) could be dissociated to a similar extent by GSH, liver gamma GCS was inhibited by GSH to a much greater extent. These results suggest that the relative sensitivity of the gamma GCS enzymes to inhibition by GSH might be related to the inherent dissociability of heavy and light subunit of gamma GCS.