Metabolic Functions of Niacin

Nicotinamide is the reactive moiety of the nicotinamide nucleotide coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate), which are coenzymes (or more correctly cosubstrates) in a wide variety of oxidation and reduction reactions (Section 8.4.1). The notation NAD(P) is used to mean either NAD or NADP, without specifying the oxidation state. 

NAD is the source of ADP-ribose for the modification of proteins by mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases (Section 8.4.2), and poly(ADP-ribosylation), catalyzed by poly(ADP-ribose) polymerase (Section 8.4.3). It is also the precursor of two second messengers that act to increase the intracellular concentration of calcium, cADP-ribose, and nicotinic acid adenine dinucleotide phosphate (Section 8.4.4). 

Nicotinic acid has been tentatively identified as the organic component of the (as yet uncharacterized) chromium-containing glucose tolerance factor that enhances the interaction of insulin with cell surface receptors. 

The notation NAD(P) is used to mean either NAD or NADP, without specifying the oxidation state. 

It is eilso the precursor of two second messengers that act to increase the intracellular concentration of calcium, cADP-ribose, tmd nicotinic acid adenine dinucleotide phosphate (Section 8.4.4). 

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In the organism that Is required In small amounts In food to sustain the normal metabolic functions of life. The key to this definition Is that this chemical compound must be supplied to the organism because the animal cannot synthesize vitamins. Lack of It produces a specific deficiency syndrome and supplying It cures that deficiency. An exception to this definition Is vitamin D, which can be made In the skin upon adequate exposure to sunlight. However, without adequate exposure, the animal Is dependent on a dietary source. Biotin, panthothenlc acid, and vitamin R are made by bacteria In the human Intestine, based on a symbiotic relation-ship and, thus, are not required by the human. Niacin can also be synthesized In humans from the amino acid tryptophane. 

The best-known functions of niacin are derived from the functions of its coenzymes NAD and NADP in the hydrogen/electron transfer redox reactions in living cells. Like most B vitamins, niacin is not extensively stored in forms or in depots that are usually metabolically inactive, but rather those that can become available during dietary deficiency. However, some storage of the coenzymes NAD and NADP in the liver is thought to occur. An inadequate dietary intake leads rapidly to significant... 

NADP can be converted to nicotinic acid adenine dinucleotide phosphate (NAADP), which has distinct functions in the regulation of intracellular calcium stores. The studies of these new roles of NAD(P) in metabolism are in their early stages, but they might soon help to better understand and explain the symptoms of niacin deficiency ( pellagra) [1]. 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Niacin is also known as vitamin PP or vitamin Bj. The term niacin describes two related compounds, nicotinic acid and nicotinamide (Figure 19.18), both with biological activity. Niacin is formed from the metabolism of tryptophan, and therefore it is not strictly a vitamin. It is a precursor of two cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for the functioning of a wide range of enzymes involved in redox reactions. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

Niacin is unusual among the vitamins in that it was discovered as a chemical compound, nicotinic acid produced by the oxidation of nicotine, in 1867 -long before there was any suspicion that it might have a role in nutrition. Its metabolic function as part of what was then called coenzyme II [nicotinamide adenine dinucleotide phosphate (NADP)] was discovered in 1935, again before its nutritional significance was known. 

Niacin is a water-soluble vitamin. The RDA of niacin for the adult man is 19 mg. Niacin is converted in the bi>dy to the cofactor nicotinamide adenine dinucleotide (NAD). NAD also exists in a phosphorylated form, NADP The phosphate group occurs on the 2-hydrr>xyl group of the AMP half of the coenzyme, NAD and NADP are used in the catalysis of oxidation and reduction reactions. These reactions are called redox reactions. NAD cycles between the oxidized form, NAD, and the reduced form, NADH + H. The coenzyme functions to accept and donate electrons. NADP behaves in a similar fashion. It occurs as NADP and NADPH + HT The utilization of NAD is illustrated in the sections on glycolysis, the malatc-aspartate shuttle, ketone body metabolism, and fatty acid oxidation. The utilization of NADP is illustrated in the sectirrns concerning fatty acid synthesis and the pentose phosphate pathway. 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

This chapter discusses the pathways by which L-tryptophan is metabolized into a variety of metabolites, many of which have important physiological functions. A few metabolites are cited here briefly. Quinolinic acid is involved in the regulation of gluconeogenesis. Picolinic acid is involved in normal intestinal absorption of zinc. The body s pool of nicotinamide adenine dinucleotide (NAD) is influenced by L-tryptophan s metabolic conversion to niacin. Finally, L-tryptophan is the precursor of several neuroactive compounds, the most important of which is serotonin (5-HT), which participates as a neurochemical substrate for a variety of normal behavioral and neuroendocrine functions. Serotonin derived from L-tryptophan allows it to become involved in behavioral effects, reflecting altered central nervous system function under conditions that alter tryptophan nutrition and metabolism. 

Niacin plays a number of essential roles in the body. It is necessary for cell respiration metabolism of proteins, fats, and carbohydrates the release of energy from foods the secretion of digestive enzymes the synthesis of sex hormones and the proper functioning of the nervous system. It is also involved in the production of serotonin, an essential... 

Water-Soluble Vitamins. Vitamin G (ascorbic acid) functions in the formation of collagen, wound healing, metabolic functions, and other roles. Foods high in vitamin G include citrus fruits, strawberries, cantaloupe, and cruciferous vegetables. B vitamins are important in energy metabolism. Thiamin (Bj) is called the antineuritic vitamin. Riboflavin (B ), rarely deficient in the diet, is found most abundantly in milk and dairy products. Niacin (Bj) is prevalent in meats, poultry, fish, peanut butter, and other foods. Other major B vitamins include folic acid (B ), B, and Bj2-... 

Vitamin Be participates in more than 100 enzymatic reactions and is needed, among other functions, for protein metabolism, conversion of tryptophan to niacin, and neurotransmitter formation. 

There is increasing evidence that niacin has potential benefit in decreasing inflammation, an important part of atherosclerosis. This may be mediated in part by ability of niacin to increase HDL or direct anti-inflammatory effect independent of the HDL (Vaccari et al. 2007a,b). For instance, administration of extended-release niacin (1000 mg/day) in 52 individuals with the metabolic syndrome was shown to be associated with a marked change of carotid intima-media thickness (IMT), improvement of endothelial function and decrease in high sensitivity C-reactive protein (Thoenes et al. 2007). 

The best-defined role of niacin is in oxidation and reduction reactions, as the functional nicotinamide part of the coenzymes NAD and NADP (section 2.4.1.3). In general, NAD is involved as an electron acceptor in energy-yielding metabolism, being oxidized by the mitochondrial electron transport chain (section 3.3.1.2), whereas the major coenzyme for reductive synthetic reactions is NADPH. An exception to this general rule is the pentose phosphate pathway of glucose metabolism (section 5.4.2), which results in the reduction of NADP to NADPH and is a major metabolic source of reductant for fatty acid synthesis (section 5.6.1). 

Transport of niacin between the liver and the intestine can occur in vivo, as indicated by radioactive probes in animals, and the liver appears to be a major site of conversion of niacin to its ultimate functional products the nicotinamide nucleotide coenzymes. Nicotinamide can pass readily between the cerebrospinal fluid and the plasma, thus ensuring a supply also to the brain and spinal cord. Liver contains greater niacin coenzyme concentrations than most other tissues, but all metabolically active tissues contain these essential... 

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