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Evaluation of L-Asparagine Metabolism in Animals and Man¹

Department of Pharmacology and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510

A rapid, sensitive, and specific method for the determination of L-asparagine and L-aspartic acid has been developed based on an enzymatically coupled oxidation of reduced pyridine nucleotide. With this spectrophotometric or fluorimetric method, the concentration of these amino acids has been determined in normal plasma, erythrocytes, tumors, urine, and cerebrospinal fluid. A modification of this method permitted measurement of 0.001 i.u. L-asparaginase. A variety of disease states in humans had relatively little effect on the levels of L-asparagine in plasma. It was shown that hepatectomy caused a two-fold elevation of plasma levels of L-asparagine in rats, but that hypophysectomy and dietary deprivation did not produce significant changes in rodents. In human subjects, however, a large oral dose of L-asparagine created a sustained elevation of the level of L-asparagine in the plasma. In an attempt to reduce plasma concentrations of L-asparagine in humans by hemodialysis, it was found that, despite extensive loss in the dialysate over a period of 6 hr, the plasma concentration was essentially unchanged. L-asparaginase treatment of a dog with lymphosarcoma caused marked objective improvement and the expected elimination of plasma L-asparagine. The levels of this amino acid in erythrocytes, urine, and tumor tissue, however, were slow to follow the changes in plasma concentration and returned to normal values much more rapidly.

¹ Supported by American Cancer Society Grant T112 H.

² On detached service from the USPHS.

³ Postdoctoral USPHS Trainee (CA 5138).

⁴ American Cancer Society Professor of Pharmacology.

Received 10/18/68. Accepted 9/18/69.

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