Proliferation-dependency of γ-glutamyl hydrolase activity in various mouse cells

The activity of γ-glutamyl hydrolase, the enzyme which deglutamylates folyl and antifolyl polyglutamates, changed significantlly in mouse cells during different phases of growth, being about two times lower in actively proliferating mice splenocytes and fibroblasts than in nondividing cells. In EAC cells growing in vivo the lowest activity was observed in cells in the logarythmic phase. Methotrexate treatment of mice in a dose of 500 mg/kg body weight increased the activity of the enzyme in EAC cells about 1.5 times. We suggest that γ-glutamyl hydrolase is a proliferating dependent enzyme which together with folylpolyglutamate synthetase ensures in cells an appriopriate amount of folates in the form of polyglutamates necessary for optimizing folate-dependent biosynthetic activities.