Niacin is present in tissues, and therefore in foods, largely as the nicotinamide nucleotides. The post-mortem hydrolysis of NAD(P) is extremely rapid in animal tissues, so it is likely that much of the niacin of meat (a major dietary source of the preformed vitamin) is free nicotinamide.
Nicotinamide nucleotides present in the intestinal lumen are not absorbed as such, but are hydrolyzed to free nicotinamide. Many intestinal bacteria have high nicotinamide deamidase activity, and a significant proportion of dietary nicotinamide may be deamidated in the intestinal lumen. Both nicotinic acid and nicotinamide are absorbed from the small intestine by a sodium-dependent saturable process.
The nicotinamide nucleotide coenzymes can be synthesized from either of the niacin vitamers and from quinolinic acid, an intermediate in the metabo-lism of tryptophan. In the liver, synthesis of the coen-zymes increases with increasing intake of tryptophan, but not preformed niacin. The liver exports nicotin-amide, derived from turnover of coenzymes, for uptake by other tissues.
The catabolism of NAD+ is catalyzed by four enzymes:
●NAD glycohydrolase, which releases nicotinamide and ADP-ribose;
●NAD pyrophosphatase, which releases nicotin-amide mononucleotide; this can be either hydro-lyzed by NAD glycohydrolase to release nicotin-amide, or reutilized to form NAD;
The activation of ADP-ribosyltransferase and poly(ADP-ribose) polymerase by toxins, oxidative stress or DNA damage may result in considerable depletion of intracellular NAD(P), and may indeed provide a protective mechanism to ensure that cells that have suffered very severe DNA damage die as a result of NAD(P) depletion. The administration of DNA-breaking carcinogens to experimental animals results in the excretion of large amounts of nicotin-amide metabolites and depletion of tissue NAD(P); addition of the compounds to cells in culture has a similar effect. Chronic exposure to such carcinogens and mycotoxins may be a contributory factor in the etiology of pellagra when dietary intakes of trypto-phan and niacin are marginal.
Under normal conditions there is little or no urinary excretion of either nicotinamide or nicotinic acid.
This is because both vitamers are actively reabsorbed from the glomerular filtrate. It is only when the con-centration is so high that the reabsorption mecha-nism is saturated that there is any significant excre-tion of niacin.
Nicotinamide in excess of requirements for NAD synthesis is methylated by nicotinamide N-methyltransferase. N1-Methylnicotinamide is actively secreted into the urine by the proximal renal tubules. N1-Methylnicotinamide can also be meta-bolized further, to yield methylpyridone-2- and 4-carboxamides.
Nicotinamide can also undergo oxidation to nico-tinamide N-oxide when large amounts are ingested. Nicotinic acid can be conjugated with glycine to form nicotinuric acid (nicotinoyl-glycine) or may be meth-ylated to trigonelline (N1-methylnicotinic acid). It is not clear to what extent urinary excretion of trigonel-line reflects endogenous methylation of nicotinic acid, since there is a significant amount of trigonelline in foods, which may be absorbed, but cannot be utilized as a source of niacin, and is excreted unchanged.