Methyl pyridone carboxamide

As shown in Figure 8.3, the principal metabolites of nicotinamide are A( -methyl nicotinamide and methyl pyridone carboxamides. AT -Methyl nicotinamide is actively secreted into the urine by the proximal renal tubules. Nicotinamide A(-methyltransferase is an S-adenosylmethionine-dependent enzyme that is present in most tissues. Very high intakes of nicotinamide may deplete tissue pools of one-carbon fragments - indeed, this was the basis for the use of nicotinamide in the treatment of schizophrenia (Section 8.8). 

Figure 8.3. Metabolites of nicotinamide and nicotinic acid. Nicotinamide deamidase (nicotinamidase), EC 3.5.1.19 nicotinamide Af-methyltransferase, EC 2.1.1.1 aldehyde dehydrogenase, EC 1.1.1.1. Relative molecular masses (Mr) nicotinamide, 123.1 nicotinic acid, 122.1 nicotinamide JV-oxide, 139.1 Af -methyl nicotinamide, 139.1 trigonelline, 137.1 nicotinuric acid, 179.2 and methyl pyridone carboxamides, 154.1.

A number of studies have investigated the equivalence of dietary tryptophan and preformed niacin as precursors of the nicotinamide nucleotides, generally by determining the excretion of -methyl nicotinamide and methyl pyridone carboxamide in response to test doses of the precursors, in subjects maintained on deficient diets. 

Urinary Excretion of N -Methyl Nicotinamide and Methyl Pyridone Carboxamide... 

The most widely used method for assessing niacin nutritional status is measurement of the urinary excretion of niacin metabolites. Table 8.1 shows the excretion of A( -methyl nicotinamide and methyl pyridone carboxamide in niacin adequacy and deficiency. 

Ratio, methyl pyridone carboxamide A/ -methyl nicotinamide ... 

The excretion of methyl pyridone carboxamide is more severely reduced in marginal niacin deficiency than is that of -methyl nicotinamide. The excretion of methyl pyridone carboxamide decreases rapidly in subjects fed on a niacin-deficient diet, and virtually ceases several weeks before the appearance of clinical signs of deficiency by contrast, a number of studies have shown continuing excretion of -methyl nicotinamide even in pellagrins. A better estimate of niacin nutritional status can be obtained by determining the ratio of urinary methyl pyridone carboxamide Ai -methyl nicotinamide, which is relatively constant, despite the administration of loading doses of tryptophan or niacin to adequately nourished subjects (between 1.3 to 4.0), and a ratio of less than 1.0 indicates depletion of niacin reserves (de Eange and Joubert, 1964 Dillon et al., 1992). 

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