The metabolic interrelationship between tryptophan, pyridoxine, and nicotinic acid; forced feeding studies in rats.

The addition of corn products to a synthetic low protein diet very low in nicotinic acid has been reported by Krehl and coworkers (1,2) to depress growth in rats. This growth retardation could be prevented by tryptophan as well as by nicotinic acid. These findings have been confirmed in this laboratory by the paired feeding technique (3) and by other investigators (4, 5). The interchangeability of nicotinic acid and tryptophan is not peculiar to corn-supplemented rations, since a similar relationship has been demonstrated with non-corn rations which are low in both trypt,ophan and nicotinic acid (6,7). The Wisconsin group has indicated that intestinal microorganisms may play a significant part in the deficiency syndrome, since the growth-depressing effect of corn can be greatly modified by the use of carbohydrates previously shown to favor intestinal synthesis (7). An increased excretion of nicotinic acid and its derivatives has been shown to result from the administration of tryptophan (4, 5, 8, 9), which has been interpreted to indicate that tryptophan may function as a metabolic precursor of nicotinic acid. The studies which have been reported on the increased excretion of nieotinic acid following tryptophan feeding have been msqde with adult rats on basal diets which contained tryptophan. It was thought desirable to compare the excretion of nicotinic acid of growing rats on an acid-hydrolyzed casein diet containing a minimum of tryptophan (0.24 mg. per gm. of diet) with that obtained with an adequate amount of tryptophan (20 mg. per rat per day) and to determine whether there is any relationship between the excretion of nicotinic acid and the gain in weight. It has been shown that in pyridoxine-deficient rats tryptophan is not normally metabolized, resulting in the excretion of xanthurenic acid in the urine (10-13). It was of interest, therefore, to study the effect of a pyridoxine deficiency on the excretion of nicotinic acid and its methylated