Effects of Dietary 6-Aminonicotinamide, an Antagonist of Nicotinamide, on the Metabolism of Tryptophan to Nicotinamide in Rats

Abstract

It has been reported that pellagra is caused by abnormal metabolism of tryptophan, although it is generally believed that pellagra is caused by a deficiency of niacin. The administration of 6-aminonicotinamide (6-AN) to rats induces central nervous lesions being similar those seen in pellagra. So, we investigated the effects of 6-AN on the metabolism of tryptophan to nicotinamide. The threshold of the toxicity of 6-AN was around 0.001% when it was incorporated in the diet. In enzyme activities involved in the metabolism of tryptophan to nicotinamide, the activities of tryptophan oxygenase and aminocarboxymuconate-semialdehyde decarboxylase were greatly increased, while that of kynureninase was decreased by feeding of 6-AN diets. In enzymes involved in catabolism of nicotinamide, the activity of nicotinamide methyltransferase was increased and those of N1-methyl-2-pyridone-5-carboxamide (2-Py)- and N1-methyl-4-pyridone-3-carboxamide (4-Py)-forming N1-methylnicotinamide (MNA) oxidases were decreased by feed...