280 THE BIOCHEMISTRY OF B VITAMINS 



taining corn grits was tripled. 74 Wintrobe 75 found a similar relationship 

 in young pigs. 



In Krehl's study it was found that -raising the casein in the basal diet 

 from a level of 15 per cent to a level of 20 per cent also prevented the 

 antagonism due to corn. Both lysine and tryptophan occur in low concen- 

 trations in corn but in higher levels in casein; and Krehl et a/. 7G found 

 that whereas lysine was not effective, 0.05 per cent of L-tryptophan was 

 as effective in reversing the effect of corn as was nicotinic acid itself. At 

 the time, this was believed to be due to intestinal synthesis of nicotinic 

 acid by bacteria, which were believed unable to grow on corn diets due 

 to inadequate tryptophan.. It was also found 77 that in diets in which 

 wheat gluten or gelatin (which are lower in tryptophan) were used as the 

 protein supplement, poor growth ensued which was cured by either trypto- 

 phan or nicotinic acid. When egg albumin, fibrin or soybean globulin were 

 used as the protein components 7S it was found that no inhibition occurred 

 when corn grits were added to the diet, and that this could be explained 

 on the basis of the high tryptophan content of these protein materials. 

 Thus, while an antagonist effect of corn was not ruled out, its low trypto- 

 phan content was at least in part concerned with the nicotinic acid- 

 deficiencies observed. 



Singal and co-workers 79 found that there was an increased urinary 

 excretion of niacin and its metabolic products in rats when tryptophan 

 was added to the corn grit diet. Rosen, Huff, and Perlzweig 80 similarly 

 observed that 50 mg of dl- or L-tryptophan either given orally or sub- 

 cutaneously produced a five- to tenfold increase in nicotinic acid excretion 

 over the level excreted on 15 per cent casein diets. Moreover, there was 

 a relative constancy of fecal nicotinic acid whether or not tryptophan 

 was administered. From these observations it became readily apparent 

 that the tryptophan effect was not due to intestinal synthesis, and that 

 tryptophan must therefore be involved in nicotinic acid metabolism, prob- 

 ably as a precursor. This, moreover, seemed more in line with the observa- 

 tion that, when 4 mg/day of 3-pyridylmethylketone, a structural 

 analogue of nicotinic acid, was fed to mice on niacin-free diets, 11 out of 

 12 died within 10 days, but that this toxic action was prevented by both 

 nicotinic acid and tryptophan. 81 This work was based on the well estab- 

 lished theory of the interference by structural analogues with the opera- 

 tion of a metabolite through saturation of enzymes involved in the 

 metabolism of the latter substance, and reversal of such toxic action by 

 precursors or products of the metabolite. It led naturally to the re- 

 emphasis of a "pellagragenic" agent in corn, which acts in a manner 

 similar to that of 3-pyridylmethylketone (Chap. VI D). More recently, 

 work with Neurospora mutants 82 makes it seem certain that the effect 



