Clearance and metabolism of plasma pyridoxal 5'-phosphate in the dog

This study was undertaken to characterize the metabolic fate of plasma pyridoxal 5'-phosphate (pyridoxal-P), the role of various organs in mediating its degradation, and the contribution of urinary excretion. Anesthetized dogs underwent sham operation, hepatectomy, nephrectomy, or combined surgical removal of the stomach, small intestine, and the spleen; however, the kinetics of plasma pyridoxal-P clearance after the intravenous administration of 2.5 mg of this B6 vitamin were not altered. In anesthetized sham-operated dogs and in unanesthetized dogs, pyridoxal (product of pyridoxal-P hydrolysis) but not 4-pyridoxic acid (oxidation product of pyridoxal) accumulated in plasma and urine after pyridoxal-P administration. Urinary excretion of pyridoxal-P was negligible and it could not account for the rapid clearance of pyridoxal-P from the plasma. The rate of pyridoxal-P hydrolysis mediated by plasma alkaline phosphatase and the cellular elements in whole blood in vitro was also too slow to account for the rapid disappearance of plasma pyridoxal-P in vivo. These results indicate that (1) normally, the overall capacity of the body to hydrolyze circulating pyridoxal-P in plasma is so large that removal of the liver, kidneys, or the intestinal tract and spleen has little or no effect on the rate of plasma pyridoxal-P decay; and (2) plasma pyridoxal-P decay normally proceeds by way of hydrolysis to form pyridoxal. Because pyridoxal is not further oxidized by the liver and the amount of pyridoxal excreted in the urine accounts for less than 25% of the pyridoxal that can be derived from the injected pyridoxal-P load, the preponderant metabolic fate of plasma pyridoxal-P most likely involves its hydrolysis to pyridoxal and then the uptake of pyridoxal by extrahepatic tissues.