Nucleoside diphosphate kinase, reaction catalyzed

Nucleoside diphosphates are converted to triphosphates by the action of a ubiquitous enzyme, nucleoside diphosphate kinase, which catalyzes the reaction... 

In summary, the nucleoside diphosphate kinase reaction is catalyzed by enzymes with broad substrate specificity many tissues show high activities of this enzyme, which is widely distributed in nature. 

The breakdown of succinyl coenzyme A may also be linked to the phosphorylation of GDP and IDP to yield GTP and ITP in the presence of inorganic phosphate. The enzyme catalyzing that reaction has been named the phosphorylating enzyme, and has been prepared in a crude form from heart muscle. This preparation also contains another enzyme, nucleoside diphosphate kinase, which catalyzes the transfer of phosphorus from GTP or ITP to ADP to yield ATP. The phosphorylation of ADP coupled to the oxidation of a-ketoglutarate is the only substrate level phosphorylation in the Krebs cycle, and, as can be expected, it is not inhibited by dinitrophenol. When O-labeled phosphate is used in the reaction, the label appears... 

ATP is the primary high-energy phosphate compound produced by catabolism, in the processes of glycolysis, oxidative phosphorylation, and, in photosynthetic cells, photophosphorylation. Several enzymes then cany phosphoryl groups from ATP to the other nucleotides. Nucleoside diphosphate kinase, found in all cells, catalyzes the reaction... 

The formation of ATP (or GTP) at the expense of the energy released by the oxidative decarboxylation of a-ketoglutarate is a substrate-level phosphorylation, like the synthesis of ATP in the glycolytic reactions catalyzed by glyceraldehyde 3-phosphate dehydrogenase and pyruvate kinase (see Fig. 14-2). The GTP formed by succinyl-CoA synthetase can donate its terminal phosphoryl group to ADP to form ATP, in a reversible reaction catalyzed by nucleoside diphosphate kinase (p. 505) ... 

Most kinases transfer chiral phospho groups with inversion and fail to catalyze partial exchange reactions that would indicate phosphoenzyme intermediates. However, nucleoside diphosphate kinase contains an active site histidine which is phosphorylated to form a phosphoenzyme.869 The enzyme catalyzes phosphorylation of nucleoside diphosphates other than ADP by a nucleotide triphosphate, usually ATP. 

If we add the equations for the reactions catalyzed by pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and nucleoside diphosphate kinase, we obtain the overall reaction for conversion of pyruvate to phosphoenolpyruvate. 

Ribonucleotide reductase activity was assayed based on CDP reduction, using a modified method of Jong et al. (1998), with the [ CICDP reduction product determined as radioactivity incorporated into DNA in a series of two coupled reactions, catalyzed by nucleoside diphosphate kinase and DNA polymerase (Klenow fragment). A 40 pi reaction mixture contained 50 mM Hepes pH 7.2, 10 mM dithiothreitol. 

ATP is synthesized in the following reaction catalyzed by nucleoside diphosphate kinase ... 

Again, the configuration is inverted. Nucleoside diphosphate kinase catalyzes the same transfer, but to a nucleoside diphosphate rather than to AMP, and with retention of configuration rather than with inversion (70). The mechanism of action of adenylate kinase involves a single displacement at P and that of nucleoside diphosphate kinase involves a double displacement at P via an intermediate phosphoenzyme. Although alkaline phosphatase is not classified as a phosphotransferase, it catalyzes transphosphorylation via the same phosphoenzyme that is the intermediate in the phosphatase reaction. This enzyme catalyzes reaction... 

Reactions (35a) and (35b) are catalyzed by galactose-1-P uridylyltransferase and UDPglucose pyrophosphorylase, respectively reactions (36a) and (36b) are catalyzed by nucleoside diphosphate kinase and adenylate kinase, respectively and reactions (37a) and (37b) are catalyzed by nucleoside phosphotransferase and adenosine kinase, respectively. 

These calculations assume that mitochondrial oxidative phosphorylation produces 1.5 ATP per FADH2 oxidized and 2.5 ATP per NADH oxidized. GTP produced directly in this step yields ATP in the reaction catalyzed by nucleoside diphosphate kinase (p. XXX). 

GMP and AMP are converted to diphosphates (see here) in reactions catalyzed by guanylate kinase and adenylate kinase, respectively. Conversion of nucleoside diphosphates to nucleoside triphosphates is catalyzed by nucleoside diphosphate kinase (see here). The reaction is reversible, thus providing a way to make both ATP and GTP. The enzyme is highly active, but has broad specificity for its phosphoryl group donor (nucleoside triphosphate) and receptor (nucleoside diphosphate). 

The addition of a third phosphate to any of the nucleoside pyrophosphates, such as UDP, is catalyzed by an enzyme found in yeast and several animal tissues. Since the reaction catalyzed by this enzyme appears to be nonspecific with respect to the base of the nucleotides, it has been named nucleoside diphosphate kinase (nudiki). The phosphate donor in this reaction may be any of the nucleoside triphosphates. As in the case of the nucleoside monophosphate kinases, there are no significant differences in the free energies of hydrolysis of the various nucleoside triphosphates, so all of the reactions are freely reversible with equilibrium constants near 1. Since the phosphorylation of nucleoside diphosphates is reversible, it is necessary that each of the corresponding triphosphates serve as phosphate donor. The phosphorylation of the monophosphates is similarly reversible, but in this case one of the sites on the enz3one appears to react only with adenine, and involves the conversion of ATP to ADP. The complementary reaction involves XMP XDP. Thus the nonadenine nucleotides are never equivalent to ATP, and the reaction is limited to the phosphorylation of a specific nucleoside monophosphate by ATP. 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

ATP also brings about the formation of other nucleoside diphosphates by the action of a class of enzymes called nucleoside monophosphate kinases. These enzymes, which are generally specific for a particular base but nonspecific for the sugar (ribose or de-oxyribose), catalyze the reaction... 

The use of GTP, UTP or CTP in a metabolic reaction or sequence is energetically equivalent to the use of ATP, because the nucleoside diphosphate that is produced is rephos-phorylated at the expense of ATP in the reaction catalyzed by nucleoside diphosphate (NDP) kinase. 

Some biosynthetic reactions are driven by the hydrolysis of nucleoside triphosphates that are analogous to ATP—namely, guanosine triphosphate (GTl ), uridine triphosphate (UTP), and cytidine triphosphate (CTP). The diphosphate forms of these nucleotides are denoted by GDP, UDP, and CDP, and the monophosphate forms are denoted by GMP, UMP, and CMP. Enzymes catalyze the transfer of the terminal phosphoryl group from one nucleotide to another. The phosphorylation of nucleoside monophosphates is catalyzed by a family of nucleoside monophosphate kinases, as discussed in Section 9.4. The phosphorylation of nucleoside diphosphates is catalyzed by 7iucleoside diphosphate kinase, an enzyme with broad... 

These reactions are catalyzed by kinases, some of viiich have already been discussed in this chapter. The reaction may be virtually irreversible as in phosphate ester formation. Here the phosphate acceptor may be a hydroi l group of a carbohydrate (glucose, ycerol, fructose, nucleotides, etc.), (Moline, or pantetheine. The terminal phosphate may also be transferred to an acceptor without loss of high chemical potential, such as to nucleoside mono- or diphosphate or to a nitro n atom. These reactions are freely reversible. Nucleotide diphosphate may also donate its terminal phosphate as in the nucleotide monophosphate kinase reaction. 

Bios5mthetic pathways of naturally occurring cytokinins are illustrated in Fig. 29.5. The first step of cytokinin biosynthesis is the formation of A -(A -isopentenyl) adenine nucleotides catalyzed by adenylate isopentenyltransferase (EC 2.5.1.27). In higher plants, A -(A -isopentenyl)adenine riboside 5 -triphosphate or A -(A -isopentenyl)adenine riboside 5 -diphosphate are formed preferentially. In Arabidopsis, A -(A -isopentenyl)adenine nucleotides are converted into fraws-zeatin nucleotides by cytochrome P450 monooxygenases. Bioactive cytokinins are base forms. Cytokinin nucleotides are converted to nucleobases by 5 -nucleotidase and nucleosidase as shown in the conventional purine nucleotide catabolism pathway. However, a novel enzyme, cytokinin nucleoside 5 -monophosphate phosphoribo-hydrolase, named LOG, has recently been identified. Therefore, it is likely that at least two pathways convert inactive nucleotide forms of cytokinin to the active freebase forms that occur in plants [27, 42]. The reverse reactions, the conversion of the active to inactive structures, seem to be catalyzed by adenine phosphoiibosyl-transferase [43] and/or adenosine kinase [44]. In addition, biosynthesis of c/s-zeatin from tRNAs in plants has been demonstrated using Arabidopsis mutants with defective tRNA isopentenyltransferases [45]. 

These reactions are catalyzed by the enzymes nucleoside monophos-phokinase and nucleoside diphosphokinase, respectively. Note that these reactions are reversible, so that ATP may be synthesized at the expense of GTP or another nucleoside triphosphate. The precursor ADP (adenosine diphosphate) may also be synthesized from the reaction of AMP with ATP, catalyzed by the enzyme adenylate kinase ... 

---