N -Methylnicotinamide

Already in 1946, Knox (46JBC699) presented evidence for the ability of a crude preparation of rabbit liver aldehyde oxidase to catalyze oxidation of diverse quaternary aromatic heterocyclic compounds. Later, it was demonstrated that mammalian liver contains an enzyme system that can oxidize N-methylnicotinamide 230 to both the pyridones 231 and 232 (64JBC2027 66BBA556 67JBC1271 67JBC1274). 

Felsted RL and Chaykin S (1967) N -methylnicotinamide oxidation in a number of mammals. Journal of Biological Chemistry 242,1274-9. 

Stanulovic M and Chaykin S (1971a) Aldehyde oxidase catalysis of the oxidation of N -methylnicotinamide and pyridoxal. Archives of Biochemistry and Biophysics 145, 27-34. 

Gershoff et al. (G3) observed no significant differences, following the ingestion of 5 g DL-tryptophan, in N -methylnicotinamide and creatinine excretion, but xanthurenic acid was lower in mongoloids than in non-mongoloid mentally retarded children. 

Xanthurenic acid and N -methylnicotinamide were measured before and after a standard DL-tryptophan load of 0.54 mg/kg, whereas xanthurenic acid and 4-pyridoxic acid were determined before and after parenteral pyridoxine hydrochloride (25 mg) plus the standard DL-tryptophan load. 

Morales and Lincoln (Mil) studied pyridoxine deficiency in 26 tuberculous children. Of these 20 received isoniazid therapy for various periods and clinical signs of Be deficiency were not observed. The ability to convert tryptophan to N -methylnicotinamide was used as a test for pyridoxine deficiency. Except for 1 case, all patients showed an increase in urinary N -methylnicotinamide excretion after tryptophan loading, and the authors admit the absence of pyridoxine deficiency. 

R. Bendayan, E. M. Sellers, and M. Silverman, Inhibition kinetics of cationic drugs on N -methylnicotinamide uptake by brush border membrane vesicles from the dog kidney cortex. Can. J. Physiol. Pharmacol., 68 467-475 (1990). 

At present, no blood markers are commonly used as indicators of niacin status. Most assessments of niacin nutriture have been based on measurement of the 2 urinary metabolites, N -methylnicotinamide and N -methyl-2-pyridone-5-carboxamide. Normally, adults excrete 20% to 30% of their niacin in the form of methylnicotinamide and 40% to 60% as the pyridone. An excretion ratio of pyridone to methylnicotinamide of 1.3 to 4.0 is thus normal, but latent niacin deficiency is indicated by a value below 1.0. As depletion occurs, the pyridone is absent for weeks before clinical signs are noted, and the methylnicotinamide excretion falls to a minimum at about the time that clinical signs are evident.f HPLC methods are currently the methods of choice, though some capillary electrophoresis methods have been developed. However, the measurement of 2-pyridone and N -methylnicotinamide concentrations in plasma may provide a more reliable metabolite ratio than urine measurements. A newer approach that may prove valuable is the ratio of NAD/NADP in erythrocytes and plasma tryptophan. A ratio of NAD/NADP below 1.0 would be indicative of a risk of developing niacin deficiency. ... 

The conversion of N-methylnicotinamide to its 6-pyridone has been studied enzymically (429). The isomeric 2-pyridone may well be formed in small amount (542), but most methods for determination do not distinguish between the isomers (e.g., 397). The 6-pyridone is not hydrolyzed to the corresponding acid (398 but see 1012). The enzyme of rat liver converting nicotinic acid to nicotinuric acid occurs in the mitochondria (454). Methylation of nicotinamide is carried out by a soluble enzyme, nicotinamide methylkinase, which has been studied by Cantoni (135, 136). The methyl group is derived from methionine. 

Cephalosporins such as cephalothin and cephaloridine interact with both the anionic (p-aminohippu-rate, PAH) and cationic (tetraethylammonium, TEA or N-methylnicotinamid, NMN) transport systems [31,67, 85]. P-lactams have been shown to be secreted by the S2 segment of the proximal tubule via the PAH transport system [85]. Cephalothin inhibited the transport of PAH in rabbit basolateral and in brush border membrane vesicles [84] while cephaloridine inhibited the transport of PAH and TEA and in rat renal cortical slices [26, 77] and of PAH [77, 84] or NMN [84] in rat brush border membrane vesicles (BBMV). 

Ouweland et al., 1978) or directly by the pyrolysis of amino acids (Fujimaki et al., 1969). Another important, if not the main, precursor of pyridines in roasted coffee is trigonelline (see Section 2.1.1.2), a product isolated by Goi ter (1910), identical to the product isolated from the seeds of Trigonella foenum-graecum. Viani and Horman (1974, 1976) identified 12 pyridinic compounds after pyrolysis of trigonelline, six of which have now been identified in roasted coffee (4-methylpyridine is noted as identified in coffee, but it is not present in the lists of quoted publications, and to our knowledge its identification has not yet been reported in the literature). The presence of four other alkyl derivatives and of two N-methylnicotinamides have not yet been confirmed in the flavor. The authors have also isolated two piperidylpyridines, 3-phenylpyridine and two of its methyl derivatives, as well as four unsubstituted and dimethyl-substituted dipyridyl compounds. 

Ricinine and ethionine were found to inhibit ricinine biosynthesis with shunting of radioactivity from [6- C]quinolinic acid through the pyridine nucleotide cycle into N-methylnicotinic acid (30) and N-methylnicotinamide (31) (c/. Scheme 6), and quinolinic acid consumption was reduced. 

N-(2-hydroxyethyl)-nicotinamide, which undergoes further side-chain degradation to nicotinuric acid and, subsequently, nicotinamide and nicotinamide metabolites (e.g., nicotinic acid and N-methylnicotinamide). The nicotinamide derived from nicorandil merges into the endogenous pool of nicotinamide adenine dinucleoside coenzymes. Its elimination half-life is approximately 1 hour. Approximately 30% of nicorandil is excreted into the urine as metabolites, with less than 1% excreted unchanged. 

Fragmentation of the pyrrolidine ring gave cis- and tmns-3-(3-pyridyl)acrylo-nitrile, N-methylnicotinamide, nicotinic acid, and products (42) and (43). ... 

Nicotinic acid and nicotinamide These are sometimes known by the generic term niacin. Their importance is in combination with tryptophan, as the coenzyme forms nicotinamide adenine dinucleotide (NAD + ) and nicotinamide adenine dinucleotide phosphate (NADP). HPLC is too insensitive to measure endogenous plasma levels, but the urinary metabolites N-methyl-2-pyridone-5-carboxylamide and N -methylnicotinamide can be measured to assess niacin status. Preliminary cleanup of urine by anion-exchange resins is followed by reversed-phase HPLC with UV detection. 

Typical urine levels. About 7-10 mg day (measured as N-methylnicotinamide). 

Strand breaks. DMSO did not induce DNA strand breaks after the first 24 h of induction although a 24 h exposure resulted in a twentyfold increase in benzidine-positive cells (Fig. 1). Analysis of DNA strand breaks by alkaline elution, showed no difference between controls and DMSO-treated cells at 0, 2, 4, 6, 8 and 12 h (data not shown). Addition of 10 mM SAB together with DMSO (Fig. 1) or the addition of SAB separately did not cause an increase in DNA strand breaks (data not shown). Sodium butyrate and N -methylnicotinamide did not induce single-strand breaks in DNA at 12 or 24 h of incubation (data not shown). Inducers of FEL differentiation and inhibitors of poly(ADP-ribose) polymerase did not cause detectable DNA strand breaks under the experimental conditions used in these studies. 

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