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Chemical Compound Review

NADPH     [(2R,3R,4R,5R)-5- [[[[(2R,3S,4R,5R)-5-(3...

Synonyms: TPNH, CHEBI:16474, bmse000055, KST-1A5819, AC1L1LCC, ...
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Disease relevance of NADPH

  • Chronic granulomatous diseases (CGDs) are characterized by recurrent infections resulting from impaired superoxide production by a phagocytic cell, nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) oxidase [1].
  • On the basis of observations with the model system, it is proposed that the cell may also decrease such toxicity by diminishing available NAD(P)H and by utilizing oxygen itself to scavenge active free radicals into superoxide, which is then destroyed by superoxide dismutase [2].
  • RESULTS: Alcoholic cirrhotics, but not patients with nonalcoholic cirrhosis or healthy subjects, had increased serum levels of immunoglobulin G and A directed against antigens produced in microsomes incubated with reduced nicotinamide adenine dinucleotide phosphate (NADPH) and ethanol [3].
  • This study determined the presence of nitric oxide synthase in the brain stem circuit controlling esophageal peristalsis by combining transsynaptic retrograde tract tracing with pseudorabies virus and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH) histochemistry [4].
  • ROS produced following angiotensin II-mediated stimulation of NAD(P)H oxidases signal through pathways such as mitogen-activated protein kinases, tyrosine kinases and transcription factors, and lead to events such as inflammation, hypertrophy, remodeling and angiogenesis [5].
  • These observations highlight the fact that NADPH oxidases are important therapeutic targets in cardiovascular disease and that, hence, there is clearly a need for the development of selective inhibitors of these enzymes [6].

Psychiatry related information on NADPH


High impact information on NADPH

  • Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain [12].
  • NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively [12].
  • Native and recombinant PAKs phosphorylated the p47phox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component in a Rac-GTP-dependent manner [13].
  • A major action of the microbicidal system of human neutrophils is the formation of superoxide anion (O2-) by a multicomponent oxidase that transfers electrons from the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to molecular oxygen [14].
  • Rap1A was found to form stoichiometric complexes with the cytochrome b558 component of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system [15].

Chemical compound and disease context of NADPH


Biological context of NADPH

  • The toxic activity in the active filtrates was not due to continuing oxidation of NADPH nor to continuing liver microsomal lipid peroxidation [22].
  • NDH-2 accomplish the turnover of NAD(P)H, regenerating the NAD(P)(+) pool, and may contribute to the generation of a membrane potential through complexes III and IV [23].
  • Src homology 3 (SH3) domains have been suggested to play an important role in the assembly of the superoxide-forming nicotinamide adenine dinucleotide phosphate (NADPH) oxidase upon activation of phagocytes, which involves the association of membrane-bound and cytosolic components [24].
  • MRA-CN forms interstrand DNA cross-links without requiring microsomal metabolic activation in the presence of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) to form a product that alkylates DNA, but MRA requires metabolic activation [25].
  • Our results reveal the first structural details of an SDR-related enzyme that catalyzes a substitutive dehalogenation reaction rather than a redox reaction, in which a halide-binding site is found at the location of the NAD(P)H binding site [26].

Anatomical context of NADPH

  • Neutrophils kill microorganisms with oxygen radicals generated by an oxidase that uses the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) as substrate [27].
  • When liver microsomes are incubated in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), their constituent lipids undergo peroxidative degeneration [22].
  • Here we found that T cells expressed a functional phagocyte-type nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [28].
  • In contrast, when solubilized membranes of the patient's neutrophils were activated with phospholipids in the absence of cytosol (Koshkin, V., and E. Pick. 1993. FEBS [Fed. Eur. Biochem. Soc.] Lett. 327:57), the rate of NADPH-dependent oxygen uptake was observed at a rate similar to that of control membranes [24].
  • The generation of reactive oxygen species (ROS) by the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex plays a critical role in the antimicrobial functions of the phagocytic cells of the immune system [29].

Associations of NADPH with other chemical compounds

  • A shift from basal to increased NAD(P)H fluorescence occurred for 18% of the cells at 1 mM glucose, for 43% at 5 mM, and for 70% at 20 mM [30].
  • NAD(P)H oxidase was more active towards NADPH (Km = 0.15 +/- 0.03 mM) than NADH (Km = 0.68 +/- 0.2 mM) [31].
  • During treatment, activities were most decreased in perivenular zones and subsequently at the periphery of the cirrhotic nodules for succinate dehydrogenase and glucose-6-phosphatase, whereas glutamate dehydrogenase and NADPH dehydrogenase were less affected [32].
  • Nitric oxide production was identified by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry [33].
  • No galanin, met-enkephalin, or NADPH diaphorase-positive cell bodies were present [33].
  • Dex at therapeutic concentrations inhibited Ab-, A23187-, or PMA-induced platelet particle formation by inhibiting platelet PLA(2), 12-LO, and NADPH oxidase [34].
  • Chelation of zinc with calcium disodium EDTA blocked both the assembly of the neuronal NADPH oxidase complex and superoxide production [35].
  • These data together suggest that the reduction of LA to DHLA using cellular NADPH may limit the capacity of the PMN NADPH oxidase to produce superoxide [36].

Gene context of NADPH

  • We suggest that the binding of an SH3 domain of p47-phox to p22-phox, and thus activation of the oxidase, does not occur in the neutrophils of this patient, although under artificial conditions, electron flow from NADPH to oxygen in cytochrome b558 is possible [24].
  • An inhibitor of NADPH-dependent oxidase 4'-hydroxy-3'-methoxy-acetophenone attenuated the rise in mRNA levels in response to TNF-alpha and aggr [37].
  • IgG and NADPH increased the transcription rates for JE/MCP-1 and CSF-1, effects inhibited by TMTU [37].
  • Both processes, and TLCS-induced Yes and EGFR activation, were sensitive to inhibition of sphingomyelinase, PKCzeta, or NADPH oxidases [38].
  • Western blots showed that DHA blocked nuclear p65 NF-kappaB subunit translocation by decreasing cytokine-stimulated reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase and PKCepsilon activities [39].
  • NADPH oxidase activation was preceded by phosphorylation of p38-kinase in As(2)O(3)-treated macrophages [40].

Analytical, diagnostic and therapeutic context of NADPH

  • Cytosolic components of the phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were detected by immunoblotting and immunocytochemical analyses with antibodies against p47-phox and p67-phox [41].
  • After 60-63 hours, brain sections were processed for viral immunofluorescence and NADPH histochemistry [4].
  • These 11 missense mutations, plus 10 others found in databases or reported elsewhere, were recreated by site-directed mutagenesis and were assessed by four assays: reduction of cytochrome c, oxidation of NADPH, support of 17alpha-hydroxylase activity, and support of 17,20 lyase using human P450c17 [42].
  • To test these models, we developed a microfluidic device capable of partially stimulating an islet, while allowing observation of the NAD(P)H and [Ca2+]i responses [43].
  • Cardiac mechanical function and myocardial iNOS, xanthine oxidoreductase (XOR), and NAD(P)H oxidase activities (sources of superoxide) were measured during the perfusion [44].


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  15. Inhibition of Rap1A binding to cytochrome b558 of NADPH oxidase by phosphorylation of Rap1A. Bokoch, G.M., Quilliam, L.A., Bohl, B.P., Jesaitis, A.J., Quinn, M.T. Science (1991) [Pubmed]
  16. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Fahey, J.W., Zhang, Y., Talalay, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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  18. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. Gorin, Y., Block, K., Hernandez, J., Bhandari, B., Wagner, B., Barnes, J.L., Abboud, H.E. J. Biol. Chem. (2005) [Pubmed]
  19. Crystal structures of Delta1-piperideine-2-carboxylate/Delta1-pyrroline-2-carboxylate reductase belonging to a new family of NAD(P)H-dependent oxidoreductases: conformational change, substrate recognition, and stereochemistry of the reaction. Goto, M., Muramatsu, H., Mihara, H., Kurihara, T., Esaki, N., Omi, R., Miyahara, I., Hirotsu, K. J. Biol. Chem. (2005) [Pubmed]
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  21. Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation. Nakamura, K., Yamagishi, S., Matsui, T., Yoshida, T., Takenaka, K., Jinnouchi, Y., Yoshida, Y., Ueda, S., Adachi, H., Imaizumi, T. Am. J. Pathol. (2007) [Pubmed]
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  29. Neutrophils from p40phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing. Ellson, C.D., Davidson, K., Ferguson, G.J., O'Connor, R., Stephens, L.R., Hawkins, P.T. J. Exp. Med. (2006) [Pubmed]
  30. Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity. Kiekens, R., In 't Veld, P., Mahler, T., Schuit, F., Van De Winkel, M., Pipeleers, D. J. Clin. Invest. (1992) [Pubmed]
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  39. The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC{varepsilon} inhibition. Massaro, M., Habib, A., Lubrano, L., Turco, S.D., Lazzerini, G., Bourcier, T., Weksler, B.B., De Caterina, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
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  41. Guinea pig gastric mucosal cells produce abundant superoxide anion through an NADPH oxidase-like system. Teshima, S., Rokutan, K., Nikawa, T., Kishi, K. Gastroenterology (1998) [Pubmed]
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