As the most important coenzymes in living organisms, NAD(H) and NADP(H) participate in more than 300 different oxidative–reductive reactions , their importance in substance metabolism and energy metabolism has long been known. Nicotinamide adenine dinucleotide (NAD) is the coenzyme form of the vitamin niacin. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all eukaryotes, bacteria, and archaea. Some enzymes, lysozyme or trypsin, for example, catalyze reactions by themselves, but many require helper substances such as coenzymes, metal ions, and ribonucleic acid (RNA). Hence, they are involved in redox reaction of the cells. This is the only pathway for the de novo NADP+/NADPH biosynthesis, thus has an important function in supplying NADP+/NADPH and regulating the level of NAD(H)/NADP(H). The precursors of NAD+ biosynthesis, such as quinolinate and nicotinic acid, do not influence NAD kinase activity in general. Thus when cells are exposed to oxidative stress, activities of key enzymes in many metabolic pathways are regulated in order to promote conversion of pro-oxidant NADH into anti-oxidant NADPH. It acts as a coenzyme in redox reactions, as a donor of ADP-ribose groups in ADP-ribosylation reactions, as a precursor of the second messenger molecule cyclic ADP-ribose, as well as acting as a substrate for bacterial DNA ligases and a group of enzymes called sirtuins that use NAD+to remove acetyl groups from proteins. Living organisms derive most of their energy from redox reactions, which are processes involving the transfer of electrons. Therefore, NAD+ is involved in the redox reactions of cellular respiration including glycolysis, TCA cycle, and electron transport chain. To realize the reasons for the differences of catalytic properties, conserved sequences and active center residues of some NAD kinases were analyzed recently . 1. For example, one of the three NAD kinase isozymes of A. thaliana, NADK2, was a chloroplast NAD kinase that can bind Ca2+/CaM . NADP+ is the used form of NADPH, and must be reduced with more electrons and a hydrogen. Multiple alignment of the primary structure of NAD kinases from several organisms The amino acid sequences of NAD kinases from Gram-negative bacteria E. coli and S. enterica, Gram-positive bacteria M. tuberculosis, B. subtilis, L. monocytogenes and M. luteus, hyperthermophilic archaeon A. fulgidus, and eukaryote S. cerevisiae (all the three enzymes of Pos5p, Utr1p and Yef1p) are aligned. In eubacterium E. coli, the 3′-phosphoadenosine 5′-phosphate phosphatase (CysQ) exhibits NADP phosphatase activity in vitro, but not in vivo . Therefore, NAD+ kinase or NADH kinase activity is required for sustaining the NADPH level to regenerate the anti-oxidative system. In comparison, NADP+ is another coenzyme which serves as an oxidizing agent in anabolic reactions including photosynthesis. More than 200 enzymes require these coenzymes for electron transfer in redox reactions. Raffaelli et al. Moreover, NADP+ also accepts a hydrogen atom or in other words, a pair of electrons, during redox reactions. The oligomeric assembly of NAD kinases may be due to their catalytic mechanism. E. coli  and Sphingomonas sp. NAD+ kinase (EC 126.96.36.199) only phosphorylates NAD+ to form NADP+; NADH kinase (EC 188.8.131.52) phosphorylates both NAD+ and NADH to form NADP+ and NADPH. Although NADP+-dependent dehydrogenases can also generate NADPH and may show positive function on anti-oxidation, they depend on a constant supply of substrate and further procession of product, hence may not be fully self-sustaining and cannot constantly supply NADPH. Here, the molecular properties, physiologic functions, and potential applications of NAD kinase are discussed. Shifting between the oxidized NAD(P) + and reduced NAD(P)H forms as it borrows hydrogens is central to many metabolic processes. The two mitochondrial isozymes, IDH and IDP1, are NAD- and NADP-specific, respectively. For example, in S. enterica  and in the mitochondria of S. cerevisiae [7,8,23,55], NAD kinase plays a major role in protecting living cells against oxidative stress. Both contain two nucleotides joined together via phosphate groups. Differences in catalytic properties and molecular structure also exist between microbial and human NAD kinases, such as phosphoryl donor specificity and molecular size of subunit. Thi… Thus, this is the main difference between NAD+ and NADP+. The third reaction is mediated by NADH kinase which directly phosphorylates NADH to form NADPH . A novel anti-oxidative defense strategies for converting NADH into NADPH inP. As many NAD kinases are allosteric enzymes, the NAD(H) and NADP(H) balance might be directly regulated by NAD kinase. The three isozymes of isocitrate dehydrogenase in Saccharomyces cerevisiae differ in subunit structure, subcellular location, and cofactor specificity. In recent years, molecular conformation of NAD kinases has been studied in order to understand their catalytic mechanisms. . It is pyridine-3-carboxylic acid, which is a component of the coenzymes NAD + and NADP +. NAD+ is the oxidized form of NAD (nicotinamide adenine dinucleotide), which is a coenzyme involved in catabolic reactions as an electron carrier. Especially, the transition of NAD to NAD+ occurs at the nitrogen molecule of the nicotinamide moiety. The most important function of NAD are these electron transferring reactions. A1 . This extra phosphate is added by NAD+ kin The role of nicotinamide adenine, or NADP, is to act as an electron carrier during the light dependent stages of photosynthesis. Moreover, they are a form of nicotinamide-adenine nucleotides. Reaction catalyzed by NAD kinase  NAD kinase catalyzes the phosphorylation of NAD(H) to form NADP(H), using ATP as phosphoryl donor. NADP+ is the oxidized form of NADP (nicotinamide adenine dinucleotide phosphate), which is a coenzyme involved in anabolic reactions similar to NAD+, transferring electrons. The initial purpose of the study on NAD kinase was to understand its regulatory properties, and speculate its influence on NAD(H)/NADP(H) metabolic flux. 60 kDa octamer of Yef1p and 60 kDa hexamer of Utr1p from S. cerevisiae [8,22], 32 kDa octamer from Candida utilis , 34 kDa octamer from pigeon liver , and 49 kDa tetramer from human . 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)]. These differences might be due to the properties of the host expression system . Intersubunit contact was significant in creating substrate binding sites and expressing NAD+- and NADH-kinase activities . Nicotinamide adenine dinucleotide phosphate. Furthermore, one ribose sugar links with an adenine nucleotide while the second ribose sugar links with a nicotinamide moiety. However, NADP participates in defense against oxidative stress , and is a substrate for the synthesis of nicotinic acid adenine dinucleotide phosphate which is a potent intracellular Ca2+-mobilizing messenger. However, up to date, no effective inhibitors have been developed that only suppress bacterial and fungi NAD kinases but not humans. “Figure 07 01 01ab” By CNX OpenStax (CC BY 4.0) via Commons Wikimedia 2. Difference Between Reversible and Irreversible... What is the Difference Between ATPase and ATP... What is the Difference Between Normal Hemoglobin and... What is the Difference Between NASH and NAFLD. 1). 3). Although more studies on NAD kinases need to be done, their important properties, physiologic functions, and potential applications have been exhibited, which opens a wide field in the basic and applied studies. All these regulation can result in effective synthesis of NADPH  (Fig. Catalyzes specifically the phosphorylation on 2'-hydroxyl of the adenosine moiety of NAD to yield NADP. Homolog genes of NAD kinase can be found in all the sequenced genomes of living organisms, including prokaryotes and eukaryotes, with the exception of the intracellular parasite Chlamydia trachomatis . Having a deficiency can cause: Deacceleration of glycolysis and Krebs’s cycle. Charged or hydrophobic amino acid residues in the corresponding position gave the stringent substrate specificity of NAD+ kinases to NAD+, whereas polar amino acid or Gly residue in the corresponding position was a prerequisite for the expression of NADH kinase activity . Although mitochondrial NADP+-dependent isocitrate dehydrogenase IDPm has an important function in the control of mitochondrial redox balance and cellular defense against oxidative damage , it depends on the support of tricarboxylic acid cycle. Detailed studies should be performed further to reveal the interactions of NAD kinase with NAD+ and ATP as its substrate, and with other ligands as its potential inhibitors. NADK1 is calmodulin (CaM) independent, and NADK2 is able to bind Ca2+/CaM, which seems to be plant specific [10,11]. NAD+ refers to a coenzyme that occurs in many living cells and functions as an electron acceptor while NADP+ refers to a coenzyme that functions as a universal electron carrier, accepting electrons and hydrogen atoms to form NADPH or nicotinamide adenine dinucleotide phosphate. Living systems have evolved numerous one-step strategies for the genesis of NADPH (Fig. Several lines of evidence presented here confirm the importance of IDH to respiratory processes. Studies on the cofactor engineering have proved that metabolic flux can be effectively regulated through controlling of key cofactors. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. NADP+/NADPH is the unsung hero of the cell’s cofactors. The higher fungi, ascomycetes and basidiomycetes, seem to produce the two distinct forms of the enzyme, the NAD‐linked and the NADP‐linked GDH. Several years ago, Gerdes et al. The structural and kinetic basis of regulation of NADPH, Primary structure of inorganic polyphosphate/ATP-NAD kinase from, Diacylglyceride kinases, sphingosine kinases and NAD kinases: distant relatives of 6-phosphofructokinases, NAD kinases use substrate-assisted catalysis for specific recognition of NAD, NAD-binding mode and the significance of intersubunit contact revealed by the crystal structure of, Acta Crystallogr F Struct Biol Cryst Commun, Nicotinamide adenine dinucleotide biosynthesis and pyridine nucleotide cycle metabolism in microbial systems, New functions of a long-known molecule. The author concluded that the NADP‐GDH function was gained by ascomycetes and basidiomycetes during evolution. Based on the elucidation of gene or genomic information in numerous living organisms, the anti-oxidative function of NAD kinase has been proved. E. coli and Sphingomonas sp. Such studies would provide useful information for designing selective inhibitors that target at microbe's NAD kinase. Because of the diversity and complexity of NAD(H)/NADP(H) metabolic pathways, NAD kinase would exhibit pleiotropic regulation for a number of reactions and pathways through controlling of NAD(H)/NADP(H) conversion. It is also a universal cofactor for numerous enzymes participating in detoxification reactions, including glutathione reductase , thioredoxin reductase and cytochrome P450 reductase. Roles are involved in: Energy metabolism, mitochondrial functions. These three NAD kinase isozymes have different functions due to particular subcellular locations, with some functions weakly rescued by their isozymes [8,9]. Describe glycolsis in terms of energy input, energy output, and net gain of ATP. NADPH is synthesized by the light reaction of photosynthesis and its reduction power is used in the dark reaction in order to assimilate carbon dioxide. Owing to these significant and distinguishable function of NAD(H) and NADP(H), their metabolism and intracellular balance must be tightly regulated. Tyr158 of domain II, whereas the conserved GGDG loop formed hydrogen bonds with the pyrophosphate group of ATP and the 2′ phosphate group of NADP+ . “Nicotinamide Adenine Dinucleotide (NAD).” Kimball’s Biology Pages, 5 Aug. 2003, Available Here2. For example, the first domain of soybean CaM plays a key role in the differential activation of pea NAD kinase . Oxford University Press is a department of the University of Oxford. Most biochemical reactions require protein catalysts (enzymes). For example, shifting from homolactic to mixed-acid fermentation in Lactococcus lactis could be modulated by the decrease of NADH/NAD+ ratios under aerobic conditions . However, the molecular size of subunit from the archaeon M. jannaschii was much larger as 64 kDa, since two distinguishable regions of NAD kinase and NADP phosphatase existed , and the sequence showed a low level of identity to those of E. coli (31%) and of M. tuberculosis (29%) . One nucleotide contains an adenine nucleobase and the other nicotinamide. NAD and NADP are two co-enzymes. NADPH can provide electrons for reductive repairing and deoxyribose synthesis. Involved in the regulation of the intracellular balance of NAD and NADP, and is a key enzyme in the biosynthesis of NADP. In Gram-positive bacteria, the activity of NAD kinases from both Bacillus licheniformis  and B. subtilis  is inhibited intensively by NADP+; the activity of NAD kinase from M. tuberculosis is also repressed greatly by NADP+ , but that from both M. tuberculosis H37Rv and M. flavus is inhibited by low concentration of NADPH . Also, each phosphate group links with a five-carbon, ribose sugar. NAD and NADP are the most abundant coenzymes in the cells, which are used in oxidation-reduction reactions. It exists in nearly all classes of living organisms and is proposed to be a primitive energy source that functions as an ATP substitute. CaM-dependent NAD kinase could play a metabolic role and participate in Ca2+-mediated cellular defense against invading pathogens in plants by helping to provide reductant for the NADPH-dependent oxidative burst . Read "Amino acid residues that determine functional specificity of NADP‐ and NAD‐dependent isocitrate and isopropylmalate dehydrogenases, Proteins: Structure Function and Bioinformatics" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. For electron transfer in redox reactions transport chain to generate ATP and may reflect organism phylogeny. 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