Regulatory Effects of Nicotinamide on Tryptophan Pyrrolase Synthesis in Rat Liver in vivo

Earlier studies had shown that the enzyme tryptophan pyrrolase which cat lyzes the first irreversible step in the conversion of tryptophan to functional nicotinyl derivatives in rat liver, was strongly inhibited by NADPH which may be considered the ultimate distal product in the conversion of tryptophan to derivatives of nicotinamide. As an extension of this work the present study has demonstrated that the administration of nicotinamide in vivo to adrenalectomized animals resulted in a strong suppression of the tryptophan‐mediated elevation of tryptophan pyrrolase but had little or no effect on the hormonal induction of this enzyme by corticosteroids. These effects of nicotinamide were in sofar specific as analogs of this compound had little or no effect on the specific tryptophan‐medidated elevation of tryptophan pyrrolase. Furthermore, the effect of nicotinamide was shown to be specific for the enzyme, tryptophan pyrrolase, having no effect on the tryptophan‐mediated increase in serine dehydratase. By means of anti‐tryptophan pyrrolase antibodies prepared in rabbits, the pulse labeling of tryptophan pyrrolase in vivo by [14C]phenylalanine showed that, in animals pre‐fed a 0% protein diet, tryptophan administration resulted in a doubling of the [14C]phenylalanine incorporation into tryptophan pyrrolase. Nicotinamide administration completely abolished this effect of tryptophan but had little effect on the dramatic stimulation of tryptophan pyrrolase synthesis by hydrocortisone. It is postulated that nicotinamide may exert its inhibitory effect on tryptophan induced synthesis of tryptophan pyrrolase at the level of genetic translation.