The influence of vitamin B6 on the formation of liver pyridine nucleotides.

It has been shown that, when tryptophan is administered to rats, an increased excretion of niacin and some of its derivatives occurs (l-4). Isotope studies by Heidelberger et al. (5, 6) have given further evidence that niacin can be derived from tryptophan in the animal body. Vitamin Bs has been implicated in this transformation, since in a pyridoxine deficiency the excretion of an abnormal metabolite, xanthurenic acid, has been observed by several workers (7-10). Both riboflavin and pyridoxine deficiencies have been shown to inhibit the excretion of niacin and quinolinic acid after the administration of either tryptophan or kynurenine (ll), implicating these vitamins in the metabolism of intermediates past kynurenine (12). However, some workers (13-15) have been unable to demonstrate a striking connection between vitamin Bg and tryptophan metabolism. Spector (15) reported that a simple pyridoxine deficiency in the rat apparently had little effect upon the conversion of tryptophan to niacin or N-methylnicotinamide as measured by the excretion of these metabolites. Investigations in this laboratory (16, 17) have shown that in the rat tryptophan appeared to be more important than niacin in maintaining liver pyridine nucleotides (PN), even though the niacin structure is present in the PN molecules. Evidence from later studies (18) indicated that a simple pyridoxine deficiency in the rat did not disturb the normal conversion of tryptophan to liver PN to any demonstrable extent. The possibility existed, however, that the pyridoxine-“deficient” rat retained enough pyridoxine in its tissues to enable the synthesis of tissue PN to take place, especially with the high levels of dietary tryptophan employed in these studies. Under these conditions the apparently low concentrations of pyridoxine in the tissues would be efficiently utilized because of the high concentrations of dietary tryptophan. For this reason it appeared important to study the transformation of niacin and tryptophan to liver PN in animals in which the effects of the pyridoxine deficiency