Phosphotransferases nucleoside phosphotransferase

This enzyme [EC 2.7.1.30], also known as glycerokinase and ATPiglycerol 3-phosphotransferase, catalyzes the reaction of ATP with glycerol to produce ADP and glycerol 3-phosphate. Both glycerone (or, dihydroxyacetone) and L-glyceraldehyde can serve as substrates. The nucleoside triphosphate can be substituted by UTP and, in the case of the yeast enzyme, ITP and GTP. 

NUCLEOSIDE PHOSPHOTRANSFERASE 2 -Deoxynucleoside 5 -monophosphate, NUCLEOSIDE PHOSPHOTRANSFERASE (DEOXY)NUCLEOSIDE MONOPHOSPHATE KINASE... 

AMP deoxythymidine 5 -phosphotransferase AMP deoxythymidine kinase adenylate-nucleoside phosphotransferase adenylic acid deoxythymidine 5 -phosphotransferase thymidine phosphotransferase... 

Nucleotides (10, 103) Various nucleoside di- and triphosphate compounds inhibit glucose-6-P phos-phohydrolase activity competitively over a broad range of pH (pH 5-8). Also function as phosphoryl donors in phosphotransferase reactions. Effects are markedly potentiated by various detergents... 

Didanosine is a synthetic purine nucleoside analog that inhibits the activity of reverse transcriptase in HIV-1, HIV-2, other retroviruses and zidovudine-resistant strains. A nucleobase carrier helps transport it into the cell where it needs to be phosphorylated by 5 -nucleoiidase and inosine 5 -monophosphate phosphotransferase to didanosine S -monophosphate. Adenylosuccinate synthetase and adenylosuccinate lyase then convert didanosine 5 -monophosphate to dideoxyadenosine S -monophosphate, followed by its conversion to diphosphate by adenylate kinase and phosphoribosyl pyrophosphate synthetase, which is then phosphorylated by creatine kinase and phosphoribosyl pyrophosphate synthetase to dideoxyadenosine S -triphosphate, the active reverse transcriptase inhibitor. Dideoxyadenosine triphosphate inhibits the activity of HIV reverse transcriptase by competing with the natural substrate, deoxyadenosine triphosphate, and its incorporation into viral DNA causes termination of viral DNA chain elongation. It is 10-100-fold less potent than zidovudine in its antiviral activity, but is more active than zidovudine in nondividing and quiescent cells. At clinically relevant doses, it is not toxic to hematopoietic precursor cells or lymphocytes, and the resistance to the drug results from site-directed mutagenesis at codons 65 and 74 of viral reverse transcriptase. 

Nucleoside phosphotransferase Flagellated protozoa Allopurinol riboside and formycin B... 

Figure 6.7 Enzymes coupling metabolism of PolyPs and nucleoside phosphates in bacteria (1) polyphosphate kinases (2) glucokinases (3) NAD kinases (4) PolyP AMP phosphotransferase (5) adenylate kinase.

In many prokaryotes, PolyP is a direct phosphorus donor for biochemical reactions due to the action of enzymes such as polyphosphate-glucose phosphotransferase and NAD kinase. Polyphosphate kinases and PolyP AMP phosphotransferase link nucleoside-polyphosphate and inorganic PolyP. Polyphosphate kinases 1 and 2 can use PolyPs for the synthesis of different nucleoside triphosphates. 

Two specific examples from Table 2 are worthy of further mention. Nucleoside phosphotransferase, which catalyzes Equation 20, had been proposed not to involve a double-displacement mechanism or an intermediate phosphoryl-enzyme. 

Purine nucleotides are probably best made by phosphorylation of the corresponding nucleosides. In recent years phosphoryl chloride has proved most convenient for this purpose and may be used with an unprotected nucleoside to give yields of about 50% (B-78MI40903, p. 827). Yields of purine nucleotides up to 60% may also be obtained using a phosphotransferase and a suitable phosphate donor with the unprotected nucleoside. Typical preparations of this type using an enzyme from wheat shoots and p-nitrophenyl phosphate as a phosphate donor have been described (B-78MI40903, p. 955). 

A/B Phosphokinases Phosphoryl group transfer Nucleoside triphosphate is 2.7.1. Phosphotransferases with an alcohol group as acceptor... 

Phosphotransfera- ses the acceptors. Compounds different than nucleoside triphosphates are the donor and some other molecules than H20 are the acceptors. 2.7.4. Phosphotransferases with a phosphate group as acceptor... 

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... 

The enzyme nucleoside phosphotransferase catalyzes reaction (20), the transfer of a phosphoryl group from one nucleoside 5 -phosphate to another nucleoside. 

In early studies the kinetics appeared to be sequential because of the convergence of double-reciprocal plots (72, 77). It was not entirely clear at the time that the phosphatase activity was an intrinsic part of the phosphotransferase activity, and the kinetics was not pursued further. Efforts to isolate an active phosphoenzyme failed, presumably due to its hydrolysis in the absence of a nucleoside 73, 77). The stereochemical analysis showing retention of configuration at phosphorus reopened the mechanistic question and stimulated further studies that... 

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. 

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