GLUTATHIONE-RELATED ENZYMES IN BRAIN IN PARKINSONS-DISEASE

The activities of enzymes related to glutathione synthesis, degradatio n, and function were analyzed in various brain regions (cerebral corte x, caudate nucleus, putamen, globus pallidus, and substantia nigra) fr om patients dying with pathologically proven Parkinson's disease (PD) and multiple system atrophy (MSA), and from matched controls with no n eurological disorder. The activity of the glutathione degradative enzy me, gamma-glutamyltranspeptidase, was selectively elevated in substant ia nigra (SN) in PD. In contrast, the activity of the synthetic enzyme , gamma-glutamylcysteine synthetase, was unaltered in SN and other bra in areas in PD. Similarly, glutathione peroxidase and glutathione tran sferase activities were unaltered in SN or in other brain regions in P D. gamma-Glutamylcysteine synthetase, gamma-glutamyltranspeptidase, gl utathione peroxidase, and glutathione transferase activities were norm al in SN and most other brain areas in MSA. However, glutathione perox idase activity was increased in the lateral globus pallidus and caudat e nucleus in MSA. The depletion of reduced glutathione (GSH) in the SN in PD, with no change in oxidized glutathione (GSSG), may be due to e fflux of GSH mainly out of glia promoted by gamma-glutamyltranspeptida se, perhaps with additional increased conversion of GSH to GSSG (which itself is transported out of cells by gamma-glutamyltranspeptidase), in response to increased hydrogen peroxide formation.