Role of Tryptophan in the Biosynthesis of Nicotinamide

Abstract

DURING an examination of the chemical mechanism of the so-called "conversion of tryptophan into nicotinamide"¹, it was hoped to obtain some elucidation of the supposed pathway from tryptophan to nicotinamide by studying in vitro the effect of various methyl-substituted tryptophans on the biosynthesis of nicotinamide by a pure strain of Bact. coli (type I fæcal²) isolated from the rat's fæces. It was found that when 2-, 4-, 5- and 7-methyl tryptophans, prepared and kindly supplied by Dr. H. N. Rydon³, and N₂-methyl tryptophan isolated from the seeds of Abrus præcatorius in concentrations of 2 mM were each incubated with the B. coli in an ammonium lactate medium⁴ containing 2 mM of L-ornithine, the first four completely inhibited the biosynthesis of nicotinamide without affecting the growth, and the N₂-methyl tryptophan behaved like tryptophan. This, indeed, indicates that tryptophan is specifically involved in the biosynthesis of nicotinamide. But recent findings showed that nicotinamide methochloride, which is eliminated after administration to dogs, rabbits or rats of DL-tryptophan-β-C¹⁴, did not contain the radioactive carbon. It therefore appears more likely that tryptophan acts as some sort of catalyst rather than by taking part directly in the reaction. To test this hypothesis the following series of experiments were carried out.