The behavior of L-asparaginase and L-asparagine in whole mice after asparaginase-application

Abstract

Healthy mice were treared intravenously with the antileukemic L-asparaginase A by a single injection of 5,000 U/kg. At various times after injection the L-asparaginase (Asnase) content was determined in the blood-plasma and in the whole body; furthermore the simultaneous content of L-asparagine (Asn) was determined in the whole animal.Methods are described for the determination of Asnase and Asn in whole mice. The Asnase activity in the blood-plasma decreased rapidly during the first 4 hours after application. Afterwards an equilibrium of distribution was apparently reached, and the further decrease followed first order kinetics with a half-life of 3 h approximately.In the whole animal, the Asnase decrease followed from the beginning first order kinetics with a half-time of 3 h. After reaching the equilibrium, the relative volume of distribution was approximately 0.1 I/kg.In untreated mice the mean total Asn content was 26 nmoles per g. After Asnase application Asn fell, in just over one hour, below the detection limit. After two days it began to reincrease slowly; only after several days the initial value was found.The experiments have shown that Asnase also exhibits its effect apart from the circulation. It is concluded that the disturbance of the blood-mediated Asn supply is not the essential effect on sensitive cells. The problem of Asnase distribution and its influence on sensitive and resistant cells is discussed with regard to the reported results.

Fungal Enzyme l-Lysine α-Oxidase Affects the Amino Acid Metabolism in the Brain and Decreases the Polyamine Level

“…T 1/2 of LO in serum was 1.23 ± 0.10 h. Most of the antitumor enzymes that are injected i.v. have similar T 1/2 in blood, for example, T 1/2 of methionine gamma-lyase from C. tetani was 1.71±0.14 and l -asparaginase from E.coli about 3 h; for l -asparaginase from E. coli it was shown that human macrophages bind and degrade this enzyme [ 16 , 17 , 18 , 19 ]. While the value of LO T 1/2 in blood is rather short, T 1/2 of LO in the brain was 9.41 ± 1.10 h. The longer persistence in the brain is possibly due to rather slow utilization of extracellular proteins in the brain.…”