Biological effects of enzymatic deprivation of L-methionine in cell culture and an experimental tumor.

Abstract

Summary An enzyme, which degrades l-methionine to methanethiol, ammonia and α-ketobutyric acid (l-methionine-α-deamino-γ-mercaptomethane-lyase or l-methioninase), isolated from Clostridium sporogenes, was found to inhibit growth of P815 cell cultures and Walker carcinosarcoma 256 of the rat. Compared with a methionine-free diet, this enzyme had greater growth-inhibiting activity and yet resulted in negligible toxicity when evaluated by weight loss of the host. One hr after a single i.v. injection of 250 units of semipurified l-methioninase the plasma levels of methionine fell rapidly to below 8% of the control but recovered almost completely within 24 hr. The half-life of the active enzyme was about 4 hr. The ratios of maximal plasma levels of active enzyme after i.v., i.p., and s.c. injection of 250 units of the enzyme per kg were 100:30:2. The ratios of maximal levels (units/g tissue) reached in liver, kidney, and spleen after a single i.v. injection were 100:50:5.