Amino Acid Imbalance and Tryptophanniacin Metabolism. I. Effect of Excess Leucine on the Urinary Excretion of Tryptophan-niacin Metabolites in Rats.

The effect of feeding excess leucine on the urinary excretion of tryptcphan-niacin metabolites and nitrogen was studied in young and adult rats. Urinary excretion of quinolinic acid and N'methylnicotinamide was increased in both young and adult rats when L-leucine was added at 1.5% level to a 9% casein diet. Quinolinic acid excretion was more markedly affected in young rats, whereas N'-methylnicotinamide excretion was more affected in adult rats. Isoleucine counteracted the effect of leucine in young rats. Nitrogen excretion increased on leucine feeding in adult rats but not in young rats. Adult rats fed a jowar (Sorghum -vulgäre")diet tended to ex crete relatively more N'-methylnicotinamide and niacin than when fed a wheat diet. The effect of leucine feeding on the uri nary excretion of tryptophan-niacin metab olites in human subjects and pellagrins has been reported by Gopalan and Srikantia (1) and Belavady et al. (2). Feeding leucine caused a significant increase in quinolinic acid excretion and a decrease in 6-pyridone of N'-methylnicotinamide excretion in normal subjects besides alter ing the excretion of other metabolites to varying degrees (2). Leucine is present in a relatively high concentration in the millet jowar (Sorghum vulgäre'). Amino acid imbalance due to an excess of leucine in jowar has been suggested as a possible factor in the development of pellagra which is endemic in certain population groups that subsist principally on this mil let (1). Amino acid imbalance in certain types of diets has been shown to cause an in crease in niacin requirement in rats and chicks (3). Addition of relatively low levels of gelatin, acid hydrolyzed protein or certain amino acids to a niacin-free casein diet has been shown to cause growth retardation in rats (4-8), which can be corrected by niacin or tryptophan. These observations have been extended to noncasein diets (9) and diets based on amino acid mixtures by Koeppe and Henderson (10). Lyman and Elvehjem (11) have shown that niacin is more effective in cor recting the imbalance than tryptophan it self, indicating that imbalance affects the efficient conversion of tryptophan to nia cin. Sauberlich and Salmon (12) showed, however, that growth retardation in ani mals due to imbalance caused by feeding casein-gelatin diet could be corrected by tryptophan and not by niacin alone. These observations would point to a dis turbance in tryptophan-niacin metabolism brought about by an amino acid imbalance in the diet, the mechanism of which is not clear. A detailed investigation of the ef fect of feeding excess leucine on trypto phan-niacin metabolism in experimental animals was considered necessary to throw some light on the mechanism of the ob served action of leucine in humans. The present paper reports such an investiga tion with rats.