Pyridine nucleotides, metabolism

Nicotinate and pyridine nucleotide metabolism in Escherichia coli and Saccharomyces cerevisiae (Unkefer and London 1984)... 

D7. Dietrich, L. S., Friedland, I. M., and Kaplan, L. A., Pyridine nucleotide metabolism mechanism of action of the niacin antagonist, 6-amino-nicotinamide. ]. Biol. Chem. 233, 964-968 (1958). 

Unkefer, C.J. and R.E. London. 1984. In vivo studies of pyridine nucleotide metabolism in Escherichia coli and Saccharomyces cerevisiae by carbon-13 NMR spectroscospy. J. Biol. Chem. 2311-2320. 

Alvarez-Gonzalez R, Juarez-Salinas H, Jacobson EL, Jacobson MK (1983) Evaluation of immobilized boronates for studies of adenine and pyridine nucleotide metabolism. Anal Biochem 135 69-77... 

Pyridine Nucleotide Metabolism as a Target for Cancer Chemotherapy... 

Pyridine nucleotide metabolism has an essential role in regulating multiple and diverse aspects of cellular metabolism ranging from carbohydrate utilization to DNA repair processes. As shown in Fig. 1, most cells convert nicotinamide to pyridine nucleotides via NMN pyrophosphorylase followed by NMN ATP adenylyltransferase. The resultant product, NAD, is used in oxidation-reduction reactions leading ultimately to the synthesis of ATP. It is also important as a co-factor for dehydrogenase enzymes that provide essential components for cell growth such as IMP dehydrogenase, whose activity is required to provide guanine nucleotides. 

Based on this pathway of cell death, it appears likely that agents which can alter NAD or ATP metabolism should be useful in sensitizing cells to the cytotoxic effects of some chemotherapeutic agents whose mechanism of action involves the production of DNA damage. Both 6-aminonicotinamide (6-AN) and Tiazofurin (Taz) have already been shown to interfere at multiple steps of pyridine nucleotide metabolism. Taz has been shown to produce the Taz analog of NAD (8, 9), to interfere with NAD synthesis and... 

The extremely low red cell NAD levels also indicate involvement of pyridine nucleotide metabolism in the clinical expression of this disorder. PP-ribose-P is require for the formation of the pyridine nucleotides NAD and NADP both are vi al to the erythrocyte. However, high, rather than low NAD levels would be anticipated and have been found by us in both HGPRT and PNP deficient red cells it is possible that the raised NAD in the latter reflect the raised PP-ribose-P levels found in PNP and HGPRT deficiency. PP-ribose-P levels were not raised in NB s red cells and the NAD values were extremely low. The latter finding may also be associated with the observed inability of the intact red cells to stimulate the re-cycling of hypoxanthine or adenine at high phosphate and suggest that NAD may be necessary for the stabilisation of erythrocyte PP-ribose-P. This would in turn... 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

The reactions in Eqs. (10) and (11) indicate the links with glucose metabolism, the former to the direct oxidative pathway, the latter to the glycolytic route. The essential link in the reduction of MHb is the generation of reduced pyridine nucleotides (B14, R12, S10). The... 

Liver cells contain two different but closely related enzymes glycerol phosphate dehydrogenase which is specific for NAD, and acylglycerol phosphate dehydrogenase, which is NADP specific. Both enzymes have B stereospecificity for the pyridine nucleotide 93. They apparently have different metabolic functions. 

It was known that the intracellular concentrations of the reduced and oxidized forms of the pyridine nucleotides vary in different cell types and under different cell culture conditions.(17) Harrison and Chance applied the NAD(P)H fluorescence technique and found that culture fluorescence can be related to the metabolic state of the cells. 18,19) Since then, more than a hundred papers on NAD(P)H fluorometry have been published. However, they are primarily divided into three major categories ... 

Tortoriello PJ, Riebow JF, Advani S, et al. 1991. The anomaly of pyridine nucleotide synergism in carbon tetrachloride metabolism. Free Radio Biol Med 10 387-396. 

The hydrogenosomal membrane displays selective permeability, thereby presenting an effective barrier to pyridine nucleotides and coenzyme A (Cerkasovov et al. 1978 Lindmark and Muller 1973 Muller 1973 Steinbiichel and Muller 1986). Transport of metabolic substrates and products across the hydrogenosomal membrane remains to be studied, but isolated T. foetus hydrogenosomes were shown to readily accumulate both radiolabeled pyruvate and malate (our unpublished data). 

Kaplan, N.O. (1985) The role of pyridine nucleotides in regulating cellular metabolism. Curr. Top. Cell. Regul. 26, 371-381. 

The roles of NADH and NADPH in the overall strategy of metabolism are shown in Fig. 5.17. Fuel molecules, such as glucose, are oxidised in catabolism they lose electrons and these reducing equivalents are transfered to an environmental acceptor such as oxygen, with concomitant ATP production (see oxidative phosphorylation, Section 5.5.6). However, some reducing equivalents are conserved and re-utilised in the synthesis of cellular components, with the consumption of ATP, as oxidised intermediates are reduced to synthetic precursors with subsequent polymerisation. The pyridine nucleotides thus have roles in both synthetic and energy generation process. 

These oxidation reactions employing pyridine nucleotides and flavoproteins are especially important in primary metabolism in liberating energy from fuel molecules in the form of ATP. The reduced coenzymes formed in the process are normally reoxidized via the electron transport chain... 

It is desirable to enhance the accuracy of the method developed for the resolution of intracellular coenzyme fluorescence spectra into their components (free vs. bound reduced pyridine nucleotides (7,8,9,10,11, 28-34), flavoproteins (35,36, 37,38). This resol utionTnay Tie important to understand ancT evaluate different metabolic steady states, drug effects, pathological conditions or divergence between cell types and their transformed variants. 

Veech R (1987) Pyridine nucleotides and control of metabolic processes. In Dolphin D, Avromovic O, Poulson R (eds) Pyridine nucleotide coenzymes. Wiley, New York, p 79... 

The pyridine nucleotide-disulfide oxidoreductases, lipoamide dehydrogenase (4), glutathione reductase (5), and thioredoxin reductase (6-8) share so many properties in common that they will be compared and contrasted before being considered separately. As their group name implies, they catalyze the transfer of electrons between pyridine nucleotides and disulfides. In spite of their similarities they function in widely divergent metabolic roles. 

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