Enzymatic decarboxylation of α-methyl amino acids

Abstract

The effects of a-methyl-(±)-ornithine and its tert-butyl ester on the survival time and the levels of polyamines in spleen tissue of mice inoculated intraperitoneally with L-1210 lymphoid leukemic cells were studied in vivo. These compounds were administered at doses of 100–300 mg/kg from Day 1 of tumor inoculation until death. This treatment neither significantly increased survival time nor altered the increases in polyamine levels normally observed during tumor growth. A method was developed to determine polyamine levels in spleen tissue. The polyamines in the tissue extracts were converted to their 5-(dimethylamino)-1-naphthalenesulfonyl derivatives, and these derivatives were separated by TLC followed by high-pressure liquid chromatography on a bonded phase microparticle column. The in vivo metabolism of 1-14C-α-methyl-(±)-ornithim was studied and compared to that of 1-14C-(±)-ornithine. 1-14C-α-Methyl-(±)-ornithine was rapidly excreted after administration to mice inoculated with L-1210 leukemic cells. Within 24 hr after injection, over 70% of the radioactive dose was found in the urine, primarily as the unchanged compound. Less than 0.1% of the administered dose appeared as 14C-labeled carbon dioxide during the 24 hr following injection. In contrast, 34% of the administered dose of 1-14C-(±)-ornithine was metabolized to labeled carbon dioxide and 28% was excreted in urine during the 24 hr following injection.