Adenosine kinase and

Ara-A is phosphorylated in mammalian cells to ara-AMP by adenosine kinase and deoxycytidine kinase. Further phosphorylation to the di- and triphosphates, ara-ADP and ara-ATP, also occurs. In HSV-1 infected cells, ara-A also is converted to ara-ATP. Levels of ara-ATP correlate directly with HSV rephcation. It has recently been suggested that ara-A also may exhibit an antiviral effect against adenovims by inhibiting polyadenylation of viral messenger RNA (mRNA), which may then inhibit the proper transport of the viral mRNA from the cell nucleus. 

Alanko, L., Heiskanen, S., Stenberg, D. Porkka-Heiskanen, T. (2003a). Adenosine kinase and 5 -nucleotidase activity after prolonged wakefulness in the cortex and the basal forebrain of rat. Neurochem. Int. 42 (6), 449-54. 

Sciotti, V. M. Van Wylen, D. G. (1993). Increases in interstitial adenosine and cerebral blood flow with inhibition of adenosine kinase and adenosine deaminase. J. Cereb. Blood Flow Metab. 13 (2), 201-7. 

Adenosine is not a classical neurotransmitter because it is not stored in neuronal synaptic granules or released in quanta. It is generally thought of as a neuromodulator that gains access to the extracellular space in part from the breakdown of extracellular adenine nucleotides and in part by translocation from the cytoplasm of cells by nucleoside transport proteins, particularly in stressed or ischemic tissues (Fig. 17-2C). Extracellular adenosine is rapidly removed in part by reuptake into cells and conversion to AMP by adenosine kinase and in part by degradation to inosine by adenosine deaminases. Adenosine deaminase is mainly cytosolic but it also occurs as a cell surface ectoenzyme. 

The purine and pyrimidine bases can be converted to then-respective nncleotides by reaction with 5-phosphoribosyl 1-pyrophosphate. Since these bases are not very soluble, they are not transported in the blood, so that the reactions are only of qnantitative significance in the intestine, where the bases are produced by degradation of nucleotides. In contrast, in some cells, nucleosides are converted back to nucleotides by the activity of kinase enzymes. In particular, adenosine is converted to AMP, by the action of adenosine kinase, and uridine is converted to UMP by a uridine kinase... 

Severe combined immunodeficiency disease The enzyme adenosine deaminase degrades deoxyadenosine which is produced during DNA degradation (Chapter 10). Deficiency of the enzyme results in accumulation of deoxyadenosine which is a substrate for adenosine kinase and leads to production of deoxyadenosine and deoxyquanosine triphosphates, which reach high concentrations. This disturbs the balance of deoxy nucleotides which results in failure of DNA replication. This enzyme is normally present in lymphocytes so that a deficiency prevents proliferation of the lymphocytes, which is essential in combatting an infection. Consequently, patients are very susceptible to infections. This is one disease that is effectively treated by gene therapy. 

Once inside the cell, the nucleoside is converted to the corresponding NMP, adenosine by adenosine kinase and uridine by uridine kinase ... 

Methoxy-, 6-ethoxy-, and 6-methylthio-9-ribofuranosyl-8-azapurines turned out to be substrates for adenosine kinase, and the first two examples were bound by adenosine deaminase. Their cytotoxic action was attributed to affinity for the kinase. 6-Imino-9-phenyl-l,6-dihydro-8-azapurine was found to be an efficient inhibitor of adenosine deaminase and guanine deaminase. Xanthine oxidase was inhibited by both this compound and 9-aryl-8-azapurin-6-ones. ° ... 

Steady state concentrations of adenosine are maintained through the activities of only three enzymes, 5 -nucleotidase (5 -N), adenosine kinase and adenosine deaminase. Adenosine kinase and adenosine deaminase were located mainly in the soluble fractions of rat cerebellar homogenates, whereas 5 -N was present in subcellular fractions (Philips and Newsholme, 1979), mainly in the synaptosomal fraction (Marani, 1977). Adenosine deaminase-immunoreactivity in rat cerebellum was present with one out of five polyclonal sera prepared by Nagy et ah (1988). Staining was present in most Purkinje cells with a variation in intensity. Staining was observed in the Purkinje cell axons and terminals in the cerebellar and vestibular nuclei. The localization of 5 -N will be discussed below. 

Phillips E, Newsholme EA (1979) Maximum activities, properties and distribution of 5 -nucleotidase, adenosine kinase and adenosine deaminase in rat and human brain. J. Neurochem., 33, 553-558. 

Nucleoside kinase inhibitors hold promise for the development of anticancer drugs by inhibition of the salvage pathway. Although previous attempts to develop these types of inhibitors into drugs have failed, the majority of these efforts focused on nucleoside analogs with poor physicochemical properties. Several non-nucleoside inhibitors have been reported for adenosine kinase and deoxycytidine kinase, with promising initial properties. It is possible that future efforts may result in the identification of non-nucleoside inhibitors that possess an appropriate efficacy-side effect profile. 

Phosphoribosyltransferase activity was found for hypoxanthine, guanine and xanthine but not for adenine (2). Adenine and guanine deaminase activities are present. Phosphorylase activities were found for adenosine, guanosine and inosine. Also present were adenosine kinase and a guanosine phosphotransferase neither inosine kinase nor phosphotransferase activity was present. The IMP dehydrogenase differs from the mammalian enzyme in that it does not require for activity and it is more sensitive to inhibition by mycophenolic acid (13). 

T.b. gambiense bloodstream forms have APRTase, HGPRTase, adenosine kinase and adenylosuccinate synthetase but lack adenosine deaminase. Two phosphorylase activities have been described for the bloodstream forms of T.b. brucei (42,50). One catalyzes the reversible phosphorolysis of adenosine, inosine and guanosine and the other is specific for adenosine and methylthioadenosine. Guanine deaminase is present whereas both adenosine and adenine deaminase are absent (8). Similar results have been reported for T. congolense (51). T. vivax is unique among the other trypanosomes in that it has an adenine deaminase (51). 

S ATP + deoxyadenosine <1-10> (<1> transfers a phospho group from specific nucleoside 5 -triphosphate donors to 5 -position of deoxyadenosine [1] <1> no activity with adenosine and guanosine [1] <2> no activity with cytidine, uridine, guanosine, deoxyguanosine and thymidine [3] <4> enzyme bears two separate but interacting active sites for deoxyadenosine and deoxycytidine kinase activity [5] <4> enzyme exists in two heterodimeric complexes, complex 1 deoxycytidine/deoxyadenosine kinase and complex II deoxyguanosine/deoxyadenosine kinase [6] <3> enzyme has both adenosine kinase and deoxyadenosine kinase activity [14]) (Reversibility <1-10> [1-9,11,12,15]) [1-9, 11, 12, 14, 15]... 

The low affinity of the AtIPTs for AMP implies that most of the natural isopentenyl riboside 5 -monophosphate (iPRMP) is formed by dephosphorylation of iPRDP and iPRTP, phosphorylation of isopentenyl riboside (iPR) by adenosine kinase, and conjugation of a phosphoribosyl moiety to iP by adenine PT [266]. Arabidopsis CYP735A1 and CYP735A2, cytocrome P450 monooxygenases, encode CK hydroxylases that catalyze tZ biosynthesis via the iPRMP-dependent pathway. The reduction of the double bond in the tZ side chain, catalyzed by a zeatin reductase, forms 6-(4-hydroxy-3-methylbutylamino)purine, whose trivial name is DZ. cZ and tZ can be enzymatically interconverted by zeatin cis-trans isomerase. 

A number of reactions which consume ATP generate AMP rather than ADP as a product, only few produce adenosine [534]. ATP may be recycled from AMP using polyphosphate-AMP phosphotransferase and polyphosphate kinase in a tandem-process at the expense of inorganic polyphosphate as phosphate donor for both steps. Alternatively, the combination of adenosine kinase and adenylate kinase were used (Scheme 2.80) [535]. 

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