niacin

Definition: Niacin, also known as nicotinic acid and vitamin B3, is the organic compound with the formula HO2CC5H4N.

This water-soluble, colourless solid is a derivative of pyridine, featuring a carboxylic acid functional group at the 3-position.

The designation vitamin B3 also includes the corresponding amide nicotinamide ("niacinamide"), wherein the CO2H group has been replaced by a CONH2 group.

Niacin is converted to niacinamide in vivo, and though the two are identical in their vitamin functions, niacinamide does not have the same pharmacologic and toxic effects of niacin, which occur incidental to niacin’s conversion.

Thus niacinamide does not reduce cholesterol or cause flushing, although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.

Niacin is a precursor to NADH, NAD, NAD+, and NADP, which play essential metabolic roles in living cells. It is involved DNA repair, and the production of steroid hormones in the adrenal gland.

Niacin is the generic designation for nicotinic acid and its functionally active derivatives (e.g., nicotinamide). In the form of nicotinamide, it is an essential component of two coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), both of which play central roles in cellular intermediary metabolism.

NAD functions as a coenzyme for a variety of dehydrogenases involved in the metabolism of fat, carbohydrates, and amino acids. NADP participates in a variety of dehydrogenation reactions, particularly in the hexose-monophosphate shunt of glucose metabolism.

Niacin can be derived from the diet or may be synthesized endogenously. It is widely available in grains, legumes, and seed oils and in much smaller quantities in meats. In some grains, it is present in bound form and therefore not absorbable; the niacin in maize (corn), in particular, is bound, so the niacin deficiency syndrome pellagra has appeared with unexpected frequency among native populations that subsist largely on maize. Niacin can also be synthesized endogenously from tryptophan.

Thus, pellagra may result from either a niacin or a tryptophan deficiency. In industrialized countries, pellagra is encountered sporadically (usually in combination with other vitamin deficiencies), principally among alcoholics and persons suffering from chronic debilitating illnesses, including HIV infection. It may also occur with protracted diarrheal states, with diets that are grossly deficient in protein, and with long-term administration of drugs such as isoniazid and 6-mercaptopurine.

In pharmacologic doses, nicotinic acid lowers plasma LDL levels by reducing hepatic synthesis of VLDL, and hence it is used in the treatment of hypercholesterolemia.

Pathology

Severe deficiency of niacin in the diet causes the disease pellagra, whereas mild deficiency slows the metabolism, causing decreased tolerance to cold.

Dietary niacin deficiency tends to occur only in areas where people eat corn (maize), the only grain low in niacin, as a staple food, and that do not use lime during meal/flour production.

Alkali lime releases the tryptophan from the corn in a process called nixtamalization so that it can be absorbed in the intestine, and converted to niacin.

The term pellagra, strictly speaking, refers to rough skin. The clinical syndrome, however, is classically identified by most clinicians by the "three Ds": dermatitis, diarrhea, and dementia.

Dermatitis is usually bilaterally symmetric and is found mainly on exposed areas of the body. The changes at first comprise redness, thickening, and roughening of the skin, which may be followed by extensive scaling and desquamation, producing fissures and chronic inflammation (Fig. 9-28). Similar lesions may occur in the mucous membranes of the mouth and vagina.

Diarrhea is caused by atrophy of the columnar epithelium of the gastrointestinal tract mucosa, followed by submucosal inflammation. Atrophy may be followed by ulceration.

Dementia results from degeneration of the neurons in the brain, accompanied by degeneration of the corresponding tracts in the spinal cord. The spinal cord lesions bear a close resemblance to the posterior column alterations observed in pernicious anemia.

Biosynthesis

Biosynthesis: Tryptophan → kynurenine → niacin

The liver can synthesize niacin from the essential amino acid tryptophan, requiring 60 mg of tryptophan to make one mg of niacin.

The 5-membered aromatic heterocycle of tryptophan is cleaved and rearranged with the alpha amino group of tryptophan into the 6-membered aromatic heterocycle of niacin.

See also

 vitamins