METABOLISM 



Melnick and his colleagues 2. * worked out a method of estimating 

 nicotinic acid, nicotinamide, nicotinuric acid and trigonelline separ- 

 ately in urine (see page 224), and used the method to study the fate of 

 ingested nicotinic acid. They found that the total free and combined 

 nicotinic acid in the urine increased when additional nicotinic acid 

 was given. Most of the increase (over 50 %) was apparently due to 

 trigonelline, a substantial proportion (36 %) to nicotinuric acid and 

 only 13 % to nicotinic acid and nicotinamide. The ingestion of nico- 

 tinamide was followed by a slower excretion of nicotinic acid com- 

 pounds, 80 to 90 % of which apparently consisted of trigonelline. 

 The excretion of trigonelline was also increased by heavy smoking or 

 by drinking coffee, so that both these sources of interference must be 

 eliminated in metabolic studies on nicotinic acid. 



These and other results obtained prior to 1943, do not, however, 

 take into account the excretion of part of the ingested nicotinic acid 

 as N^-methylnicotinamide and N^-methyl-6-pyridone-3-carboxylamide, 

 which were discovered subsequently ; the values reported for the 

 urinary trigonelline probably included the N^-methylnicotinamide and 

 the pyridone. 



Rats were said to convert a substantial proportion of ingested 

 nicotinic acid into trigonelline and nicotinuric acid, only a small 

 amount being excreted unchanged.^ Nicotinamide was apparently 

 excreted mainly as trigonelline (but see below). 



Somewhat similar results were obtained with dogs,® which appar- 

 ently excreted trigonelline and nicotinuric acid as the principal end- 

 products of nicotinic acid metabolism. On a blacktongue-producing 

 diet, the amount of (apparent) trigonelline excreted fell to o-i mg. 

 per day and several 25-mg. doses of nicotinic acid were required to 

 increase the output to normal levels. On a diet containing i-i mg. 

 of nicotinic acid per kg., 50 % was excreted in the urine, 90 % of it 

 in the form of (apparent) trigonelline. After saturation with nico- 

 tinic acid, loo-mg. doses of nicotinamide were completely excreted 

 as (apparent) trigonelline (75 to 94 %) and nicotinuric acid (6 to 

 25 %). Neither trigonelline nor nicotinuric acid was utilised by the 

 dog. 



Rabbits excreted 1-54 mg. of nicotinic acid per day or 077 mg. 

 per kg. of bodyweight per day in the urine when maintained on a 

 normal diet, but less than half that amount on a pellagra-producing 

 diet ; the urinary excretion increased on administration of nicotinic 

 acid.'^ According to M. Swaminathan,^ rabbits on a diet low in 

 nicotinic acid (07 mg. per kg.) excreted 0-15 mg. of nicotinic acid 

 and o-o86 mg. of (apparent) trigonelline in the urine daily, and almost 

 similar amounts in the faeces. When given extra nicotinic acid, 15 

 to 20 % of it was excreted in the urine. 



253 



