Recently, studies on the survival strategies of Pseudomonas fluorescens in oxidative environment proved that NAD kinase was requisite for the controlling of NAD(H)/NADP(H) balance, especially the sufficient supply of NADPH, to adapt to environmental variance [50–52], suggesting the critical role of NAD kinase on adjusting NAD(H)/NADP(H) coenzyme in the metabolic networks. NADPH. 4). Studies showed that each subunit of M. tuberculosis NAD kinase consisted of an N-terminal α/β domain and a C-terminal 12-stranded β sandwich domain, connected by swapped β strands [31]. But the oxidoreductase enzymes that use NAD rarely use NADP (and vice versa). NAD kinase catalyzes the phosphorylation of NAD(H) to form NADP(H), using ATP as phosphoryl donor. Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN, is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent. Nicotinamide adenine dinucleotide has several essential roles in metabolism. To realize the reasons for the differences of catalytic properties, conserved sequences and active center residues of some NAD kinases were analyzed recently [34]. A1) could only phosphorylate NAD+, whereas NAD kinases from Gram-positive bacteria (e.g. Several lines of evidence presented here confirm the importance of IDH to respiratory processes. The first reaction is catalyzed by NADP+-dependent dehydrogenases, such as isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malate enzyme, and glutamate dehydrogenase (GDH) [45,46]. There are three NAD kinases in yeast Saccharomyces cerevisiae, with Pos5p in mitochondrial matrix, and Utr1p and Yef1p in cytoplasm [7,8]. Therefore, NAD+ kinase or NADH kinase activity is required for sustaining the NADPH level to regenerate the anti-oxidative system. Although the physiologic functions, influence pathways, and regulatory mechanisms of NAD kinases have not been clearly elucidated, some of their characteristics, functions, and potential applications have been revealed. For example, ATP–NAD kinase utilizes ATP as the sole phosphoryl donor for NAD(H) phosphorylation; NTP-NAD kinase uses ATP as well as some other nucleoside triphosphates such as GTP, CTP, UTP, and ITP; poly(P)/NTP-NAD kinase utilizes NTP as well as inorganic polyphosphates [poly(P)]. The most important function of NAD are these electron transferring reactions. Here, the molecular properties, physiologic functions, and potential applications of NAD kinase are discussed. Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme present in biological systems. They are responsible for transferring electrons in between biochemical reactions. “NADP+ phys” By NEUROtiker – Own work (Public Domain) via Commons Wikimedia, Lakna, a graduate in Molecular Biology & Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things, What is the Difference Between NAD+ and NADP+, What are the Similarities Between NAD+ and NADP+. Although mitochondrial NADP+-dependent isocitrate dehydrogenase IDPm has an important function in the control of mitochondrial redox balance and cellular defense against oxidative damage [45], it depends on the support of tricarboxylic acid cycle. Here only the oxidized form of NAD(P)+ is shown. Both NAD and NADP are structurally similar but, NADP contains a phosphate group. fluorescens(modified from Singhet al.50)  MDH, malate dehydrogenase; NADK, NAD kinase; ME, malic enzyme; PC, pyruvate carboxylase; PEPCK, phosphoenolpyruvate carboxykinase; PK, pyruvate kinase; ICL, isocitrate lyase; MS, malate synthase. NAD+ is reduced to NADH in both glycolysis and TCA cycle, and the reducing power of NADH is used to generate ATP in the electron transport chain. 30 kDa hexamer from E. coli [20], 32 kDa dimmer from Sphingomonas sp. Emerging roles of NAD in cellular signaling, Alpha-5,6-dimethylbenzimidazole adenine dinucleotide (alpha-DAD), a putative new intermediate of coenzyme B12 biosynthesis in, Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine, Sources of NADPH in yeast vary with carbon source, Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP, The power to reduce: pyridine nucleotides–small molecules with a multitude of functions, The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of, Ocular lens NAD kinase: partial purification and metabolic implications, A novel strategy involved anti-oxidative defense: the conversion of NADH into NADPH by a metabolic network, Oxidative stress evokes a metabolic adaptation that favors increased NADPH synthesis and decreased NADH production in, Metabolic adaptation and oxaloacetate homeostasis in, NADP(H) phosphatase activities of archaeal inositol monophosphatase and eubacterial 3′-phosphoadenosine 5′-phosphate phosphatase, Cofactor engineering: a novel approach to metabolic engineering in, NAD kinase levels control the NADPH concentration in human cells, Developmental ontogeny of NAD kinase in the rat conceptus, Toxic DNA damage by hydrogen peroxide through Fenton reaction, Detection of reactive oxygen species via endogenous oxidative pentose phosphate cycle activity in response to oxygen concentration: implications for the mechanism of HIF-1alpha stabilization under moderate hypoxia, Calmodulin activates NAD kinase of sea urchin eggs: an early event of fertilization, Calmodulin-dependent NAD kinase of human neutrophils, Differential activation of NAD kinase by plant calmodulin isoforms, Transgenic tobacco expressing a foreign calmodulin gene shows an enhanced production of active oxygen species, Enhanced dihydroflavonol-4-reductase activity and NAD homeostasis leading to cell death tolerance in transgenic rice, Proline metabolism and NAD kinase activity in green bean plants subjected to cold-shock, Chloroplast NAD kinase is essential for energy transduction through the xanthophyll cycle in photosynthesis, Stress induces the expression of AtNADK-1, a gene encoding a NAD(H) kinase in, Identification of 113 conserved essential genes using a high-throughput gene disruption system in, A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown function, Probing binding requirements of NAD kinase with modified substrate (NAD) analogues. 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