Nicotinamide adenine dinucleotide niacin metabolism

Four of the B vitamins are essential in the citric acid cycle and therefore in energy-yielding metabolism (1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor in the a-ketoglutarate dehydrogenase complex and in succinate dehydrogenase (2) niacin, in the form of nicotinamide adenine dinucleotide (NAD),... 

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. 

Nicotinate and nicotinamide, together referred to as niacin, are required for biosynthesis of the coenzymes nicotinamide adenine dinucleotide (NAD"") and nicotinamide adenine dinucleotide phosphate (NADP" ). These both serve in energy and nutrient metabolism as carriers of hydride ions (see pp. 32, 104). The animal organism is able to convert tryptophan into nicotinate, but only with a poor yield. Vitamin deficiency therefore only occurs when nicotinate, nicotinamide, and tryptophan are all simultaneously are lacking in the diet. It manifests in the form of skin damage (pellagra), digestive disturbances, and depression. 

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. 

Nicotinamide (8.45) and nicotinic acid (8.46, niacin)—which have also been referred to as vitamin B3 or B5—are simple pyridine-3-carboxylic acid derivatives occurring in liver, yeast, and meat. In the form of nicotinamide-adenine dinucleotide (NAD" ) or its phosphorylated form (NADP+), nicotinamide is the most important electron carrier in intermediary metabolism. Unlike FAD, it adds a hydride ion (i.e., one pair of electrons and one hydrogen) only. 

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. 

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 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. 

It is not strictly correct to regard niacin as a vitamin. Its metabolic role is as the precursor of the nicotinamide moiety of the nicotinamide nucleotide coenzymes, nicotinamide adenine dinucleotide (NAD) and NADP, and this can also be synthesized in vivo from the essential amino acid tryptophan. At least in developed countries, average intakes of protein provide more than enough tryptophan to meet requirements for NAD synthesis without any need for preformed niacin. It is only when tryptophan metabolism is disturbed, or intake of the amino acid is inadequate, that niacin becomes a dietary essential. 

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 of the electrons removed from fuels during energy metabolism are transferred via nicotinamide adenine dinucleotide (NAD). NAD collects electrons from many different energy fuels in reactions catalyzed by specific enzymes. These enzymes are dehydrogenases. Reduced NAD, in turn, shuttles the electrons to the respiratory chain. Flavin adenine dinucleotide (FAD) also acts as an electron shuttle. In each reaction involving NAD (or FAD), two electrons are transferred that is, two electrons are carried or shuttled. NAD and FAD are small molecules with molecular weights of 663 and 785 and are manufactured in the body from the vitamins niacin and riboflavin, respectively. These molecules are called N.A.D. and F.A.D., not nad" or Jad. ... 

Co-enzyme I (nicotinamide-adenine dinucleotide NAD) and Co-enzyme II (nicotinamide-adenine dinucleotide phosphate NADP) are required by all living cells. They enable both the conversion of carbohydrates into energy as well as the metabolism of proteins and fats. Both nicotinamide and nicotinic acid are building blocks for these co-enzymes. The common name for the vitamin is niacin and, strictly speaking, refers only to nicotinic acid. 

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. 

Nicotinic acid (niacin) is a precursor of nicotinamide adenine dinucleotide (NAD) which plays a central role in metabolism as a coenzyme. It can be synthesized from tryptophan. Tryptophan and nicotinate deficiency lead to pellagra, which is characterized by diarrhea, dermatitis, and dementia. Maize-rich diets... 

Nicotinamide adenine dinucleotide (NAD) is the coenzyme form of the vitamin niacin. Most biochemical reactions require protein catalysts (enzymes). Some enzymes, lysozyme or trypsin, for example, catalyze reactions by themselves, but many require helper substances such as coenzymes, metal ions, and ribonucleic acid (RNA). Niacin is a component of two coenzymes NAD, and nicotinamide adenine dinucleotide phosphate (N/kDP). NAD (the oxidized form of the NAD coenzyme) is important in catabolism and in the production of metabolic energy. NADP (the oxidized form of NADP) is important in the biosynthesis of fats and sugars. 

The absorption of niacin in the human body mainly occurs in the stomach and small intestine (Bechgaard and Jespersen 1977). Niacin is taken up by the body swiftly and quickly, and reaches peak plasma levels within 30-60 minutes of being absorbed (Bodor and Offermanns 2008). Furthermore it has a plasma half-life of 60 minutes (Carlson et al. 1968 Svedmyr and Harthon 1970). The enzyme nicotinamide adenine dinucleotide (NAD) glycohydrolase, which is found in the intestine and liver, faciUtates the synthesis of nicotinamide from NAD (Henderson and Gross 1979). This is an important step that ensures the availability of nicotinamide for the conversion to NAD. Niacin is metabolized in most tissues in the body and its metaboKtes are excreted in urine (Jacob et al. 1989 Shibata and Matsuo 1989). Importantly, niadn deficiency occurs mainly as a result of poor diet, but also other conditions such as carcinoid syndrome, Hartnup s disease and drug intake (isoniazid) (Hegyi et al. 2004). 

Nicotinic acid (niacin) and various nicotinamides are sources of the coenzyme nicotinamide adenine dinucleotide, synthesized in the mitochondria and vital for oxidative energy production in many metabolic reactions. The RDA is 15-20 mg, normally acquired from a balanced diet of meat, fish, whole cereals and yeast. Peas, beans, nuts, fruit and vegetables are all good sources of this vitamin. 

Metabolism—Niacin is readily absorbed from the small intestine into the portal blood circulation and taken to the liver. There it is converted to the coenzyme nicotinamide adenine dinucleotide (NAD). Also, some NAD is synthesized in the liver from tryptophan. NAD formed in the liver is broken down, releasing nicotinamide, which is excreted into the general circulation. This nicotinamide and the niacin that was not metabolized in the liver are carried in the blood to other body tissues, where they are utilized for the synthesis of niacin-containing coenzymes. 

In the metabolism of carbohydrates, thiamin diphosphate is needed in the conversion of pyruvic acid and the sub uent formation of acetyl coenzyme A, which in turn enters the Krebs cycle and produces vital energy. This is one of the most complex and important reactions in carbohydrate metabolism. In addition to thiamin diphosphate, it also requires the following cofactors coenzyme A, which contains pantothenic acid, nicotinamide adenine dinucleotide (NAD), which contains niacin magnesium ions and lipoic acid. 

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