NAD pyrophosphatase

Figure 8.2. Synthesis of NAD from nicotinamide, nicotinic acid, and qninolinic acid. Quinolinate phosphoribosyltransferase, EC 2.4.2.19 nicotinic acid phosphoribosyl-transferase, EC 2.4.2.11 nicotinamide phosphoribosyltransferase, EC 2.4.2.12 nicotinamide deamidase, EC 3.5.1.19 NAD glycohydrolase, EC 3.2.2.S NAD pyrophosphatase, EC 3.6.1.22 ADP-ribosyltransferases, EC 2.4.2.31 and EC 2.4.2.36 and poly(ADP-ribose) polymerase, EC 2.4.2.30. PRPP, phosphoribosyl pyrophosphate.

NAD pyrophosphatase, which releases nicotinamide mononucleotide. This can either be hydrolyzed by NAD glycohydrolase to release... 

The total NADase activity of tissues from these four enzymes is very high, and the total tissue content of nicotinamide nucleotides can be hydrolyzed within a few minutes. Two factors prevent this in vivo. Apart from NAD pyrophosphatase, the enzymes that catalyze the release of nicotinamide from NAD(P) are biosynthetic rather than catabolic, and their activity is highly regulated under normal conditions. Furthermore, the values of K n of the enzymes are of the same order of magnitude as those of many of the NAD(P)-dependent enzymes in the cell, so that there is considerable competition for the nucleotides. Only that relatively small proportion of the nicotinamide nucleotide pool in the cell that is free at any one time will be immediately available for hydrolysis. 

Nicotinamide is incorporated into NAD and nicotinamide is the primary ckculating form of the vitamin. NAD has two degradative routes by pyrophosphatase to form AMP and nicotinamide mononucleotide and by hydrolysis to yield nicotinamide adenosine diphosphate ribose. 

Abbreviations. a-M, a-mannosidase AP, acid phosphatase as-ni-ATPase, anion-stimulated, nitrate-inhibitable ATPase CCR, NAD(P)H-dependent cytochrome oreduc-tase cs-vi-ATPase, cation-stimulated, vanadate-inhibitable ATPase, CAT, catalase GS 1/11, glucan synthase 1 or 11 IDPase, inosine diphosphatase cs-PPase, cation-stimulated pyrophosphatase RNA polymerase, DNA-dependent RNA polymerase TP-25, 25 kDa tonoplast integral protein. 

Fig. 6. Distribution of the most common folds in selected bacterial, archaeal, and eukaryotic proteomes. The vertical axis shows the fraction of all predicted folds in the respective proteome. Fold name abbreviations FAD/NAD, FAD/NAD(P)-binding Rossman-like domains TIM, TIM-barrel domains SAM-MTR, S-adenosylmethionine-dependent methyltransferases PK, serine-threonine protein kinases PP-Loop, ATP pyrophosphatases. mge, Mycoplasma genitalium rpr, Rickettsiaprowazekii hh x, Borrelia burgdorferi ctr, Chlamydia trachomatis hpy, Helicobacter pylori tma, Thermotoga maritima ssp, Synechocystis sp. mtu, Mycobacterium tuberculosis eco, Escherichia coli mja, Methanococcus jannaschii pho, Pyrococcus horikoshii see, Saccharomyces cerevisiae, cel, Caenorhabditis elegans.

This enzyme [EC 1.1.1.23] catalyzes the reaction of l-histidinol with two NAD+ to produce L-histidine and two NADH. L-Histidinal will also serve as a substrate for this protein. The Neurospora crassa enzyme will also catalyze the reactions of phosphoribosyl-AMP cyclohydrolase [EC 3.5.4.19] and phosphoribosyl-ATP pyrophosphatase [EC 3.6.1.31]. 

It should be noted that many PolyP-dependent enzymes (polyphosphate kinase, exopolyphosphatases, PolyP glucokinase and NAD kinase) are multifunctional and can catalyse reactions both with PolyPs and nucleotide triphosphates. Some PolyP-dependent enzymes, especially exopolyphosphatases, provide excellent examples of cell-compartment specific enzymes. Cell-compartment specificity is a characteristic feature of eucaryotic ATPases (Nelson, 1992) and pyrophosphatases (Baltscheffsky and Baltscheffsky, 1992 Davies et al, 1997 Baykov et al, 1999). This means that the same reaction may be performed in cell compartments by specific enzymes, which differ in their properties, encoding genes and functions. All of the above properties of PolyP-dependent enzymes suggest their important role in the regulation of living cell functions as a whole. 

From FDP, a phosphatase or pyrophosphatase catalyzes the removal of the pyrophosphate group, generating famesol (Fig. (5)). The next two steps, oxidation of this alcohol to an aldehyde (famesal), then a carboxylic acid (famesoic acid), are catalyzed by one or two NAD+-dependent dehydrogenase(s) [63]. In the cockroach, D. punctata, methylation of... 

Functional Stability of Microsomes. The coenzyme NADPH is required by yS mixed-function oxidases. Unfortunately the yS contain other enzymes that will oxidase NADPH or destroy it and adversely affect drug detoxification. The most Important among these are NAD(P)ase, NAD(P)H pyrophosphatase, and NAD(P)H oxidase. We added the competitive inhibitors sodium pyrophosphate and nicotinamide to reaction mixtures to block the effects of NAD(P)H pyrophosphatase and NAD(P)ase, respectively (10, 11). 

Nucleosidediphosphatase [Nucleosidediphosphate phosphohydrolase] (3.6.1.6) is produced and catalyzes the reaction A nucleoside diphosphate + H2O = a nucleotide + orthophosphate. [Acts on IDP, GDP, UDP and also on D-ribose 5-diphosphate.] Nucleotide pyrophosphatase [Dinucleotide nucleotidohydrolase] (3.6.1.9) is produced and catalyzes the reaction A dinucleotide + H2O = 2 mononucleotides. [Substrates include NAD" " NADP ", FAD, CoA and also ATP and ADP.] Deoxycytidinetriphosphatase [dCTP nucleotidohydrolase, Deoxy-CTPase, dCTPase] (3.6.1.12) is produced and catalyzes the reaction dCTP + H2O = dCMP + pyrophosphate. [Also hydrolyses dCDP to dCMP and orthophosphate]... 

Ibe nicotinamide moiety of NAD is biosynthesized from quinolinic acid (see Pyridine nucleotide cycle. Tryptophan). NAD is degraded by a pyrophosphatase, and by nucleosidases that cleave the glycosidic bonds to nicotinamide and adenine. 

To determine the structure of arylazido- 3-alanine NAD, the analog is treated with nucleotide pyrophosphatase isolated from potatoes as described by Kornberg and Pricer. After incubation of the arylazido-/8-alanine NAD with pyrophosphatase, the products are separated on Whatman No. 1 filter paper with n-butanol-water-acetic acid (5 3 2). A single UV absorbing spot with Rf value of 0.18 and two orange spots with Rf values of 0.60 and 0.91 were evident (Table III). The orange material with the highest Rf value (0.91) was characteristic of arylazido-yS-alanine. 

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