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Amino Acid Levels following L-Asparagine Amidohydrolase (EC.3.5.1.1) Therapy¹

Sloan-Kettering Institute for Cancer Research and the Sloan-Kettering Division Graduate School of Medical Sciences, Cornell University Medical College, New York, New York 10021

The blood levels of the dicarboxylic amino acids and their amides were determined at various periods during the course of L-asparaginase treatment of a number of patients with asparaginase-sensitive and asparagine-insensitive malignancies. Asparagine levels decreased rapidly at the start of treatment, falling essentially to zero with low levels of enzyme. Glutamine levels also dropped rapidly, reaching zero a day or two after the asparagine levels had done so. At this time the glutamate usually reached a peak level; in one case, glutamate was four times the normal level. The results of complete amino acid analyses revealed no remarkable changes in the concentrations of any other amino acid. Glutamine began to reappear as soon as the initial course of therapy (200 IU/kg/day) was interrupted, whereas asparagine levels remained negligible until the plasma asparaginase level was no longer measurable. Study of the bloods of a number of patients being maintained in hematologic remission for a period of months on continuing dosage of enzyme (10 or 50 IU/kg/day) revealed essentially normal glutamine levels in all cases. The body can apparently overcome the effect of at least 50 IU/kg of this Escherichia coli L-asparaginase preparation on the serum glutamine level, possibly because this falls within normal synthetic capacity or because of an increase in glutamine synthetase levels following inital therapy at asparaginase levels high enough to cause large drops in the blood glutamine levels. The observed sensitivity of the tumor to asparaginase could not be correlated with any changes in the amino acid levels during therapy.

¹ This investigation was supported in part by funds from USPHS Grant No. CA-08748.

Received 4/24/68. Accepted 9/ 4/68.

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