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Increased Tyrosine Phenol-Lyase Activity in Mice following Pyridoxal Phosphate Administration¹

Department of Pharmaceutical Sciences, School of Pharmacy, University of Washington, Seattle [G. W. E., L. M., G. G. M.], and the Pacific Northwest Research Foundation, and The Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [D. H. S., V. R.]

A limiting factor in the depletion of plasma tyrosine following tyrosine phenol-lyase injection into normal mice was found to be the availability of an essential cofactor, pyridoxal phosphate. Because of the extremely short half-life of this cofactor, adequate elevation of circulating cofactor levels for prolonged periods by injection of a pyridoxal phosphate solution was not practical. Similarly, long-term diets enriched with pyridoxine and pyridoxal phosphate did not significantly improve the efficiency of the injected holoenzyme. A repository dosage form was devised that consisted of an s.c. implant of pyridoxal phosphate suspended in a spermaceti and peanut oil mixture. Under these conditions a sustained increase in holoenzyme activity levels and a significant resulting decrease in plasma tyrosine levels were obtained.

¹ These studies were supported in part by Institutional Cancer Grant IN-26 and Grant PDT-73 from the American Cancer Society.

² To whom requests for reprints should be addressed.

³ Present address: College of Pharmacy, Washington State University, Pullman, Wash. 99163.

Received 4/ 6/78. Accepted 7/31/78.