Increased tyrosine phenol-lyase activity in mice following pyridoxal phosphate administration

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.