Protease activities in normal and schizophrenic human prefrontal cortex and white matter

Endo- and exopeptidase activities have been measured in normal post-mortem human prefrontal cortex and subjacent white matter to estimate their relative capabilities for protein and peptide degradation. Cathepsin D and three dipeptidases versus leucyl-glycine, glycyl-l-leucine and glycyl-glycine) were assayed in serial, microtome prepared frozen sections (± 125 g fresh weight) and related to histological composition (Nissl stain), dry weight, total protein, and DNA content. RNA concentrations were similarly determined, serving as approximate indices of protein synthetic potential. Cathepsin D activity and RNA concentration were, respectively, threefold and twofold greater in cortical gray than in subcortical white matter. Each dipeptidase showed somewhat higher activity in white matter than in cortex. In both tissues the order of activities were: glycyl-leucine> glycyl-glycine>leucyl-glycine dipeptidase. The results are consistent with preferential localizations of cathepsin D in cortical neurons and dipeptidases in neuroglia. None of the four enzymes showed differences in activity in comparable cortex from six patients with chronic schizophrenia.