Quinolinic acid excretion and metabolism in man.

In 1946, Rosen e2 al. (1) showed that administration of tryptophan to rats resulted in an additional excretion of nicotinic acid and Nl-methylnicotinamide (Nl-Me). Singal et al. (2) found, in addition to these, increased excretion of another metabolite which could be converted to nicotinic acid by autoclaving in 1 N sulfuric acid solution. Henderson isolated this metabolite from the urine of rats receiving tryptophan, identified it as quinolinic acid, and showed that it was partially decarboxylated to nicotinic acid by the treatment employed by Singal et al. (2) ; he converted it quantitatively to nicotinic acid by autoclaving in glacial acetic acid (3). Increased quinolinic acid excretion following tryptophan administration has also been noted in man (4-6), the dog (7), and other animals (8). The place of quinolinic acid in the conversion of tryptophan to nicotinic acid has not been established (9-12). Quinolinic acid is partially converted to nicotinic acid compounds in the rat (9, lo), and can replace, to a limited extent, the nicotinic acid requirement of the rat for growth (9, 11). Neurospora mutants utilize quinolinic acid poorly in place of nicotinic acid (9, 11). Neurospora and rat liver slices can convert 3hydroxyanthranilic acid (an intermediate in the synthesis of nicotinic acid in Neurospora) to quinolinic acid (11, 12). .The present experiments were undertaken to learn whether quinolinic acid is a precursor of nicotinic acid in man, and, if so, to try to ascertain its importance in the conversion of tryptophan to nicotinic acid. The effect of quinolinic acid administration upon the urinary excretion of nicotinic acid metabolites was studied in man and compared with the findings following tryptophan supplements. Data on the excretion of quinolinic acid by subjects on various diets and after test doses of tryptophan are also presented.