Extracellular purine metabolism

Zimmermann, Herbert

doi:10.1002/(sici)1098-2299(199611/12)39:3/4<337::aid-ddr15>3.0.co;2-z

Cited by 159 publications

(147 citation statements)

References 127 publications

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“…They are characterized by two sequence motifs: motif A, DXH(X) ∼25 -GDXXD(X) ∼25 GNH[D/E], and a shorter motif B, GH-(X) ∼50 GHX[H/X]. In mammals, these include in addition to eN the Ser/Thr protein phosphatases and tartrateresistant acid phosphatase [289,290]. Molecular cloning revealed phylogenetic relationships between vertebrate eN and functionally related enzymes in invertebrates, yeasts/ fungi, eubacteria, and archaea but seem to be lacking in plants [201,202,240].…”

Section: Phylogenetic Relationshipmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

872

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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Section: Phylogenetic Relationshipmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

872

922

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“…The metabolism of nucleosides is well understood in the brain [30,41,[71][72][73][74][75][76][77]. Purines and pyrimidines are synthesized (de novo) from precursor molecules such as carbon dioxide, aspartate, 5-phosphoribosyl-1-pyrophosphate (PRPP), glutamine, glycine and formyl groups, as well as from aspartate and carbamyl-phosphate.…”

Section: The Nucleoside System In the Brainmentioning

confidence: 99%

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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“…Since ATP is rapidly metabolized by extracellular ectoATPase to yield ADP and adenosine [23], it is possible to speculate about the involvement of ATP metabolites in ATPinduced cell death. To test this hypothesis, ADP, adenosine and ATPgS were intrastriatally injected.…”

Section: Discussionmentioning

confidence: 99%

ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors

et al. 2002

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The present study examined the in vivo e¡ects of ATP on the striatum of Sprague^Dawley rats. Intrastriatal administration of ATP produced dose-dependent striatal lesions as con¢rmed by cresyl violet staining. Additional immunostaining using neuronal nuclear protein (NeuN), OX-42 and GFAP antibodies revealed that ATP caused death of both neurons and glial cells. The nonmetabolizable ATP analogue ATPgS and P2X receptor agonist a,b-methylene ATP (a,b-MeATP) mimicked ATP e¡ects, whereas either P2Y receptor agonist ADP or P1 receptor agonist adenosine did not. The P2 receptor antagonist reactive blue 2, but not pyridoxal-phosphate-6 -azophenyl-2 0 ,4 0 -disulphonic acid (PPADS) attenuated ATP-induced striatal injury. These results suggest that intrastriatal administration of ATP causes P2X receptor-mediated cell death in the striatum and support the hypothesis that extracellular ATP can be an important mediator of neuropathological events of brain injuries. NeuroReport13:1611^1615

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Extracellular purine metabolism

Cited by 159 publications

References 127 publications

Cellular function and molecular structure of ecto-nucleotidases

Cellular function and molecular structure of ecto-nucleotidases

The Antiepileptic Potential of Nucleosides

ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors

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