Nicotinic adenine nucleotide

The most common desaturase in most organisms, including insects, is stearoyl Co A desaturase, which introduces a double bond in the 9-10 position of long-chain fatty acids (2JL). Similarities between this enzyme and the All desaturase from cabbage looper include location in the microsomal fraction, lack of sensitivity to carbon monoxide, inhibition by cyanide, use of a reduced nicotine-adenine nucleotide cofactor as an electron source and use of 16 and 18 carbon acids as preferred substrates. 

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 most generally interesting intracellular metabolites are the adenine nucleotide phosphates (ATP/ADP/AMP) and the nicotinic acid/adenine dinucleotide phosphates (NAD(P)H/NAD(P)). The pool concentrations and ratios of these can serve as markers for the physiological status of a culture. 

Nicotine adenine dinucleotide ( diphosphopyridine nucleotide ) appears to be necessary in this transformation, although none of the reduced form accumulates E. S. Maxwell, J. Am. Chem. Soc., 78, 1074 (1056) see also. Ref. 125. 

In most bacteria and in higher plants nicotinic acid is formed from aspartic acid and a three carbon unit derived from glycerol, probably D-glyceraldehyde-3-phosphate (D 2). A key intermediate is quinolinic acid, which in animals, however, is derived from l-tryptophan (D 21). Nicotinic acid originates from quinolinic acid via nicotinic acid mononucleotide formed with the participation of 5-phosphoribosyl-l-pyrophosphate. It changes either directly to nicotinic acid or is formed via nicotinamide adenine dinucleotide (NAD+) in the nicotinic acid nucleotide cycle. 

The chemistry of NAD and NADP. Nicotin adenine dinucleotides NAD and NADP are composed of two nucleotides joined through their phosphate groups by a phosphoanhydride bond. 

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... 

NAD A Coenzyme Nicotinamide adenine dinucleotide (NAD) is one of the principal oxidation-reduction reagents in biological systems. This nucleotide has the structure of two D-ribose rings (a dmucleotide) linked by their 5 phosphates. The aglycone of one ribose is nicotinamide, and the aglycone of the other is adenine. A dietary deficiency of nicotinic acid (niacin) leads to the disease called pellagra, caused by the inability to synthesize enough nicotinamide adenine dinucleotide. 

The nicotinamide nucleotide coenzymes function as electron carriers in a wide variety of redox reactions. In addition, NAD is the precursor of adenine dinucleotide phosphate (ADP)-ribose for ADP-ribosylation and poly(ADP-ribosylation) of proteins and cADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). They act as second messengers and stimulate increases in intracellular calcium concentrations. 

Figure 6. Proposed pyridine nucleotide cycle. Abbreviations NaMN, nicotinic acid mononucleotide NaAD, nicotinic acid adenine dinucleotide and NAD, oxidized form of nicotinamide adenine dinucleotide.

Nicotinamide-adenine dinucleotide (NAD diphosphopyri-dine nucleotide) and nicotinamide-adenine dinucleotide phosphate (NADP also termed triphosphopyridine nucleotide) represent most of the niacin activity found in good sources that include yeast, lean meats, liver, and poultry. Milk, canned salmon, and several leafy green vegetables contribute lesser amounts but are still sufficient to prevent deficiency. Additionally, some plant foodstuffs, especially cereals such as corn and wheat, contain niacin bound to various peptides and sugars in forms nutritionally not readily available (niacinogens or niacytin). Because tryptophan is a precursor of niacin, protein provides a considerable portion of niacin equivalent. As much as two thirds of niacin required by adults can be derived from tryptophan metaboHsm via nicotinic acid ribonucleotide... 

Nicotinic acid or nicotinamide (i) Nicotinamide adenine dinucleotide (ii) Nicotinamide adenine dinucleolide phoiphaie (iii) Nicotinamide mononucleotide Hydrogen Hydrogen Hydrogen (i) Nicotinic ncid or nicotina-roidc 0i) Nucleotides of nicotinamide PtnicUlium spent mycelium Wheat seeds Uver... 

Azaserine, a glutamine antagonist," is known to inhibit the NAD synthetase reaction in which nicotinic acid adenine dinucleotide is converted into NAD with glutamine or ammonia as the nitrogen donor. ° When azaserine or azaleucine was fed to Ricinus communis plants followed by [6- C]quinolinic acid, a marked decrease in incorporation of radioactivity into ricinine was observed with azaleucine, less so with azaserine." Both azaserine and azaleucine were found also to inhibit the incorporation of [6- " C]quinolinic acid into pyridine nucleotide cycle intermediates [in the case of azaserine the conversion of nicotinic acid dinucleotide into nicotinamide adenine dinucleotide (NAD ) was apparently inhibited]. 

Nicotinic acid was first identified as an essential dietary supplement in 1937. It can be found in an active form as either free nicotinic acid, the amide derivative or bound to the pyridine-containing nucleotides (nicotinamide adenine dinucleotide (NAD) and the corresponding phosphate ester (NADP)). 

A number of compounds are capable of altering the rate of purine biosynthesis Je novo. Many that are capable of inhibiting purine biosynthesis Je novo appear to do so as a result of depletion of intracellular levels of PRPP (7). In most of these cases, the nucleotide derivative of the compound is formed and this derivative may also play a role in the inhibition of the PRPP amidotransferase and/or PRPP synthetase. Examples include adenine, allopurinol, 2 6-diaminopurine, nicotinic acid, and orotic acid. On the other hand, several compounds have been studied which lead to an acceleration in the rate of purine biosynthesis apparently mediated by an increased level of PRPP (7). Examples of this category might include fructose, methylene blue, ACTH, TSH, and estrogens. 

Quinolinic acid phosphoribosyl transferase (PT) catalyzes the formation of nicotinic acid mononucleotide (NaMN) from quinolinic acid and phosphoribosyl pyrophosphate. The pyridine nucleotide NaMN reacts with ATP (adenosine Hiphos-phate) upon mediation of NaMN adenylyltransferase to form the nicotinic acid adenine dinucleotide (NaAD) (Figure 6.7). The latter is converted to NAD by NAD synthetase. NADP is formed from NAD by the catalysis of NAD kinase. 

Figure 6.37. A metabolic grid proposed for the biosynthesis and control of metabolism of ricinine. A1—quinolinic acid A2—nicotinic acid mononucleotide A3—nicotinic acid adenine dinucleotide A4—nicotinamide adenine dinucleotide A5—nicotinamide A6—nicotinic acid A7—nicotinamide mononucleotide B1— AT-demethjiiicinine B2— ricinine Cl— N-methylnicotinic acid and C2— AT-methylnicotinamide. pyridine nucleotide cycle and postulated reaction sequence (Nowacki and Waller 1975a). Courtesy of Pergamon Press, Ltd., copyright 1975.

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