Tryptophan-Niacin Metabolism in Alloxan Diabetic Rats

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Abstract
It has been shown that there is a marked reduction in the conversion of tryptophan to NMN in the alloxan diabetic rat. The primary failure appears to be in the conversion of tryptophan to niacin rather than in the methylation or excretion of the metabolite, since administration of niacin, niacinamide or NMN did result in increased urinary NMN. The failure to convert tryptophan to niacin appeared to result primarily from the diabetes per se rather than from some more direct effect of the alloxan, since the defect was corrected in some rats by administration of insulin, and alloxan treated rats which failed to become diabetic converted tryptophan to NMN as did normal rats. In some diabetic animals the conversion of niacinamide to NMN was also reduced, but to a lesser extent than was the conversion of tryptophan to NMN. Administration of tryptophan elevated the blood glucose in fasting diabetic rats, but not in normal controls, suggesting that part of the tryptophan may be converted into glucose in an attempt to meet energy requirements. However, the lack of a beneficial effect of dietary fructose in correcting the low conversion of tryptophan to NMN, indicates that conversion to glucose is not the entire explanation. Some diabetic animals in which the conversion of tryptophan to NMN was greatly impaired did excrete increased amounts of NMN when very large doses of tryptophan (400 mg) were given, indicating that the defect may be due to changes in the primary metabolic pathways of tryptophan rather than to absence of the proper mechanisms. Diabetics excreted much more xanthurenic acid than did non-diabetics, following large doses (200 to 400 mg) of tryptophan.