BIOSYNTHESIS 



that it can replace tryptophan in promoting the growth of rats ^^ and 

 that it is converted into nicotinic acid and quinolinic acid by rat liver 

 slices.^2 Quinolinic acid was excreted by rats following intraperitoneal 

 injection of 3-hydroxyanthranilic acid or L-tryptophan.^^ An analo- 

 gous series of transformations to the foregoing has been shown to take 

 place with certain micro-organisms (see page 281). That L-kynure- 

 nine, but not kynurenic acid, is an intermediate in the synthesis of 

 nicotinic acid is confirmed by the observation that the former, but not 

 the latter, increased the N^-methylnicotinamide excretion in rats.^^ 



The supporters of the contrary view, that tryptophan merely 

 stimulates the synthesis of nicotinic acid by intestinal bacteria, are 

 P. Ellinger and M. M. Abdel Kader.^^ They observed that, although 

 a mixed culture from rats' caecum was apparently able to produce 

 nicotinamide from tryptophan, Escherichia coli was not able to effect 

 this transformation in the absence of lactate, whereas ornithine and, 

 to a smaller extent, glutamine and arginine were readily converted 

 into nicotinamide. The synthesis was completely inhibited by 2-, 4-, 

 5- and 7-methyltryptophan. Since more N^-methylnicotin amide was 

 excreted when tryptophan was given to rats orally than when given 

 parenterally, and since less w^as excreted when the animals were given 

 sulphasuxidine, it was concluded that the nicotinamide was synthe- 

 sised by the intestinal flora and that the precursor was ornithine, 

 not tryptophan ; it is suggested that the latter is a catalyst stimu- 

 lating the formation of ornithine. 



These two views are not irreconcilable and, in any event, none of 

 the evidence advanced in support of the intestinal synthesis hypo- 

 thesis is opposed to the view that tryptophan can be converted into 

 nicotinic acid directly in the tissues of animals. 



The recognition of L-tryptophan as a precursor of nicotinic acid 

 makes it necessary to assume that pellagra can only occur where 

 there is deficiency of both nicotinic acid and typtophan in the diet. 

 By feeding two normal adults on a diet of known nicotinic acid content 

 and estimating the urinary output of N^-methyl-G-pyridone-a-car- 

 boxylamide (page 255) and other nicotinic acid metabolites, W. I. M. 

 Holman and D. J. de Lange ^^ found that the ingestion of 12 g. of 

 L-tryptophan over the test period increased the nicotinic acid output 

 by 145 and 181 mg, in the two individuals. This implies that the 

 tryptophan in the diet, normally equal to about i-i g. per day, may 

 be of great importance in the prevention of pellagra. 



References to Section 9 



I. R. W. Luecke, W. N. McMillen, F. Thorp and C. Tull, /. Nutrition, 



1948, 36, 417 ; F. Rosen and W. A. Perlzweig, /. Biol. Chem., 



1949, 177, 163. 



251 



