EFFECTS OF DIETARY 6-AMINONICOTINAMIDE, AN ANTAGONIST OF NICOTINAMIDE, ON THE METABOLISM OF TRYPTOPHAN TO NICOTINAMIDE IN RATS

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 see n in pellagra. So, we investigated the effects of 6-AN on the metaboli sm of tryptophan to nicotinamide. The threshold of the toxicity of 6-A N was around 0.001% when it was incorporated in the diet. In enzyme ac tivities involved in the metabolism of tryptophan to nicotinamide, the activities of tryptophan oxygenase and aminocarboxymuconate-semialdeh yde decarboxylase were greatly increased, while that of kynureninase w as decreased by feeding of 6-AN diets. In enzymes involved in cataboli sm of nicotinamide, the activity of nicotinamide methyltransferase was increased and those of N-1-methyl-2-pyridone-5-carboxamide (2-Py)- an d N-1-methyl-4-pyridone-3-carboxamide 4-Pyridone-3-carboxamide (4-Py)- N-1-methylnicotinamide (MNA) oxidases were decreased by feeding of 6-A N diets. These changes were similar those seen in alloxan- and strepto zotocin-induced diabetic rats. The urinary excretion ratio of (2-Py 4-Py)/MNA, which is reported to be lower in pellagrin than in normals, was decreased, and the conversion ratio of tryptophan to nicotinamide was also decreased. These results demonstrated that the metabolism of tryptophan to nicotinamide was greatly changed by intake of 6-AN.