Nicotinamide coenzyme 5 -Nicotine

Nicotinamide and nicotinic acid are both white crystalline substances. Their aqueous solution has a maximal UV absorbance at 263 nm. Both vitamers have the same biological activity as they can be converted into each other. Figure 2 shows the structure of the coenzyme forms NAD+ and NADP+. 

Niacin Nicotinic acid, nicotinamide Coenzyme in oxidation and reduction reactions, functional part of NAD and NADP Pellagra—photosensitive dermatitis, depressive psychosis... 

Garrett RH, Grisham CM (1995) Nicotinic acid and the nicotinamide coenzymes. In Biochemistry. Saunders, Orlando, p 468... 

Niacin, which refers to nicotinic acid and nicotinamide, is the metabolic precursor to three nicotinamide coenzymes. These are essential for the activity of a large number of enzymes catalyzing redox reactions. Pellagra is a niacin deficiency disease. 

Niacin is present in foods mainly as coenzyme NAD and NADP, which are hydrolyzed in the intestine, and it is adsorbed as nicotinamide or nicotinic acid. The free forms, nicotinamide and nicotinic acid, only allowed to be added in fortified foods [403], occur naturally in limited amounts. Instead, niacin occurs as nicotynil ester bonded to polysaccharides, peptides, and glycopeptides. In general, niacin is widespread in foodstuffs (cereals, seeds, meat, and fish). High concentrations are present in roasted coffee beans as a primarily product of the roasting process [417]. 

The niacin vitamers in foods include nicotinic acid and nicotinamide (Fig. 4), which occur in limited quantities in the free form, and their coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) (93,96). The nicotinic acid analog of NAD as well as nicotinamide and nicotinic acid mononucleotides also occur in nature. In addition, niacin occurs as nicotinyl esters bound to polysaccharides, peptides, and glycopep-tides, which are known as niacytin and niacynogens, respectively. In general, the niacin vitamers in cereal grains and other seeds are principally the nicotinic acid forms, whereas those in meat and fish are primarily the nicotinamide forms (94,95). 

Figure 8.1. Niacin vitamers, nicotinamide and nicotinic acid, and the nicotinamide nucleotide coenzymes. Relative molecular masses (Mr) nicotinic acid, 123.1 nicotinamide, 122.1 NAD, 663.4 and NADP 743.4.

The biological importance of these compounds stems from their use as cofactors. Both nicotinamide and nicotinic acid are building blocks for coenzyme I (Co I), nicotinarnide—adenine dinucleotide (NAD) (3) and coenzyme 11 (Co II), nicotinamide—adenine dinudeotide phosphate (NADP) (4) (2). 

Niacin and niacinamide (nicotinamide and nicotinic acid amide) are converted to the ubiquitous redox coenzymes nicotinamide-adenine dinucleotide (NAD)" and nicotinamide-adenine dinucleotide phosphate (NADP). ... 

Vitamin B3. Obsolete name for nicotinic acid, nico-tinamide (see also nicotinamide coenzymes), and pantothenic acid. 

Vitamin B3 Vitamin B3 (niacin) has different physiologically active forms, nicotinic acid, nicotinamide, and their coenzymes, which are very stable at ambient temperature. Usually acid or alkaline hydrolysis are used to convert nicotinamide to nicotinic acid for quantitation of both vitamers as nicotinic acid the first treatment (acid) is used to quantitate biologically available niacin, while alkaline hydrolysis provides an estimate of the total niacin content. Nicotinic acid has been analyzed using ion exchange or RP chromatography with amino columns. Detection is performed with UV absorbance at 254 nm. 

The conversion of nicotinamide to nicotinic acid requires the activities of a deaminase and a ribonucleotide pyrophosphorylase. Although a detailed description of mechanisms controlling NAD coenzyme synthesis in mammalian tissues is not available, it has been suggested that the regulatory restraints are... 

Preformed niacin occurs in foods either as nicotinamide (niacinamide) or as the pyridine nucleotide coenzymes derived from it, or as nicotinic acid, without the amide nitrogen, which is the form known as niacin in North America. Both nicotinamide and nicotinic acid are equally effective as the vitamin, but in large doses they exert markedly different pharmacological effects, so it is important, at least in that context, to make and maintain the distinction. In addition to the preformed vitamin, an important in vivo precursor is the amino acid L-tryptophan, obtained from dietary protein. Because the human total niacin supply, and hence niacin status, depends on the dietary tryptophan supply as well as on the amount of preformed dietary niacin and its bioavailability, it has become the accepted practice to express niacin intakes as niacin equivalents, ... 

Of the two pyridine nucleotide coenzymes, NAD is present mainly as the oxidized form in the tissues, whereas NADP is principally present in the reduced form, NADPH2. There are important homeostatic regulation mechanisms which ensure and maintain an appropriate ratio of these coenzymes in then-respective oxidized or reduced forms in healthy tissues. Once converted to coenzymes within the cells, the niacin therein is effectively trapped, and can only diffuse out again after degradation to smaller molecules. This implies, of course, that the synthesis of the essential coenzyme nucleotides must occur within each tissue and cell type, each of which must possess the enzymatic apparatus for their synthesis from the precursor niacin. Loss of nicotinamide and nicotinic acid into the urine is minimized (except when the intake exceeds requirements) by means of an efficient reabsorption from the glomerular filtrate. 

Most foods of animal origin contain nicotinamide in the coenzyme form (high bioavialability). Liver and meat are particularly rich in highly bioavailable niacin. Most of the niacin in plants, however, occurs as nicotinic acid in overall lower concentrations and with a lower bioavailability. The major portion of niacin in cereals is found in the outer layer and its bioavailability is as low as 30% because it is bound to protein (niacytin). If the diet contains a surplus of L-tryptophan (Ttp), e.g., more than is necessary for protein synthesis, the liver can synthesize NAD from Trp. Niacin requirements are therefore declared as niacin equivalents (1 NE = 1 mg niacin = 60 mg Trp). 

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. 

Nicotinic acid derivatives occur in biologic materials as the free acid, as nicotinamide, and in two coenzymatic forms nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes act in series with flavoprotein enzymes and, like them, are hydrogen acceptors or, when reduced, donors. Several plants and bacteria use a metabolic pathway for the formation of nicotinic acid that is different from the tryptophan pathway used by animals and man (B39). 

Recently nicotinic acid has been found to lower serum cholesterol in hypercholesteremia, and also in normal persons and rabbits (A3, F2). It was shown that the hypercholesteremia, induced by a 48-hour fast, could be completely corrected by giving the animals large doses of nicotinic acid during the fast. In contrast to nicotinic acid, nicotinamide does not lower the cholesterol level (M10). Several explanations are offered for the action of nicotinic acid (1) it inhibits cholesterol biosynthesis, (2) it interferes with coenzyme A, and (3) it involves a hitherto unknown pharmacologic effect. The renewed clinical interest in nicotinic acid induced us to look for a more specific and sensitive assay for nicotinic acid (B7, M8). 

Although the structures for molecules having niacin activity are simple, the forms in which they act in human biochemistry are not so simple. Nicotinic acid and nicotinamide are precursors for three complex coenzymes in multiple oxida-tion/reduction (redox) reactions nicotinamide mononucleotide, NMN nicotinamide adenine dinucleotide, NAD+ and nicotinamide adenine dinucleotide phosphate, NADP. I shall use NAD+ as representative of the class. NADH is the corresponding reduced form. ... 

Niacin the generic name for nicotinic acid and nicotinamide precursors for the coenzymes NAD+ and NADP+. 

Nicotinic acid and nicotinamide are precursors of the coenzymes NAD+ and NADP+, which play a vital role in oxidation-reduction reactions (see Box 7.6), and are the most important electron carriers in intermediary metabolism (see Section 15.1.1). We shall look further at the chemistry of NAD+ and NADP+ shortly (see Box 11.2), but note that, in these compounds, nicotinamide is bound to the rest of the molecule as an A-pyridinium salt. 

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. 

The alkaloids are also relevant to drug design. Alkaloids are complex heterocyclic compounds that contain nitrogen and thus have base-like (hence the term alkaloid ) properties they are extremely structurally diverse. Nicotine is one of the simplest alkaloids. Oxidation of nicotine produces nicotinic acid, a vitamin that is incorporated into the important coenzyme nicotinamide adenine dinucleotide, commonly referred to as NAD" (oxidized form). The neurotransmitter serotonin is an alkaloid containing the aromatic indole ring system. 

Two vitamins, nicotinamide and pyridoxine (vitamin B6), are pyridine derivatives. Nicotinamide participates in two coenzymes, coenzyme I (65 R = H) which is known variously as nicotinamide adenine dinucleotide (NAD) or diphosphopyridine nucleotide (DPN), and coenzyme II (65 R = P03H2) also called triphosphopyridine nucleotide (TPN) or nicotinamide adenine dinucleotide phosphate (NADP). These are involved in many oxidation-reduction processes, the quaternized pyridine system acting as a hydrogen acceptor and hydrogen donor. Deficiency of nicotinamide causes pellagra, a disease associated with an inadequately supplemented maize diet. Nicotinic acid (niacin) and its amide are... 

Nicotinic acid can be converted to nicotinamide in Ihe body and, in this form, is found as a component of two oxidation-reduction coenzymes (Fig. 2) nh olimiinide adenine dinuclentide (NAD) and nicotinamide adenine dinucleolide phosphine NADP). The nicotinamide portion of the coenzyme iransfers hydrogens by alternating between an oxidized quaternary nitrogen and a reduced tertiary nitrogen. See Fig. 3. 

This reaction is a good example of the interrelationship of vitamin B coenzymes. Four vitamin coenzymes are necessary for this one reaction (1) thiamine (in TPP) for decarboxylation (2) nicotinic acid in nicotinamide adenine dinucleotide (NAD) (3) riboflavin in flavin adenine dinucleotide (FAD) and (4) pantothenic acid in coenzyme A (CoA) for activation of die acetate fragment. 

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). 

The physiologically active forms of niacin are nicotinic acid, nicotinamide, and their coenzymes (93,96). Niacytin and the niacynogens appear to have limited bioavailability, although more work is needed in this area. The absorption and metabolism of niacin has been reviewed (20,93). 

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