Niacin metabolic functions

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. 

Biochemically, the niacin coenzymes function as cofactors for a number of dehydrogenases due to their oxidation-reduction capabilities (19,93,96). They are involved in the metabolism of carbohydrates, fatty acids, and amino acids. Nicotinamide can also participate in nonredox reactions, such as the ribosylation of ADP. 

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. 

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-... 

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. 

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]. 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

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. 

Niacin is a generic term which refers to two related chemical compounds, nicotinic acid (6.22) and its amide, nicotinamide (6.23) both are derivatives of pyridine. Nicotinic acid is synthesized chemically and can be easily converted to the amide in which form it is found in the body. Niacin is obtained from food or can be synthesized from tryptophan (60 mg of dietary tryptophan has the same metabolic effect as 1 mg niacin). Niacin forms part of two important co-enzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are co-factors for many enzymes that participate in various metabolic pathways and function in electron transport. 

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. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

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. 

The antipellagra vitamin, essential to many animals for growth and health. In humans, niacin is believed necessary, along with other vitamins, for the prevention and cure of pellagra. It functions in protein and carbohydrate metabolism. As a component of two important enzymes, coenzymes I and II, it functions in glycolysis and tissue respiration. 

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. 

---