Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first demonstrations in the early seventies that adenosine had marked effects in the cerebral cortex, which were independent of its role in intermediary metabolism and could be antagonised by methylxanthines, were followed by the observations that other purine derivatives, notably ATP, may also play a critical role in cell function. In 1978 Burnstock first introduced the terms Pl for the nucleoside receptors and P2 for the nucleotide receptors, based on the most fundamental divisions of purine receptors between those for nucleosides such as adenosine and those for nucleotides such as ATP. At present, the P1 (adenosine) receptor family presents 4 subtypes, while the P2 (ATP, ADP and UTP) receptor family has been divided into P2X ionotropic receptors and P2Y metabotropic G protein-coupled receptors (GPCRs). While knowledge on the purinergic receptor pharmacology was increasing, the development of potent and selective ligands for these receptors has been a target of medicinal chemistry research for several decades. In particular, synthesis of 2-substituted adenosines was carried out in many laboratories starting from seventies aimed at finding adenosine derivatives more resistant than the parent nucleoside to rapid uptake into cells, to deamination by adenosine deaminase, and to phosphorylation by adenosine kinase. In the present review the synthesis of alkynyl derivatives of adenine, adenosine, N-alkylcarboxamidoadenosine, and adenine nucleotides, which have been tested on purinergic receptors, will be summarized. Furthermore, the contribution of chemistry, molecular modelling, and pharmacology to the development of structure-activity relationships in this class of purinergic receptor ligands will be outlined.
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PMID:The importance of alkynyl chain presence for the activity of adenine nucleosides/nucleotides on purinergic receptors. 2142 96

Adenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of the salvage pathways which reduce the loss of intracellular purine and pyrimidine rings. Although this could explain the role of these enzymes, it poses a problem of the role of the cytosolic 5'-nucleotidase. Why are nucleosides produced from nucleoside-monophosphates, only to be converted back to the same compounds? To date, it is well established that a cross talk exists between the extracellular and intracellular nucleoside metabolism. In districts, such as brain, which are dependent on salvage nucleotide synthesis, nucleosides are produced through the action of the ecto-5'-nucleotidase, the last component of a series of plasma-membrane bound enzyme proteins, catalyzing the successive dephosphorylation of released nucleoside-triphosphates. Both nucleosidetriphosphates (mainly ATP and UTP) and nucleosides (mainly adenosine), act as extracellular signals. Once transported into cell cytosol, all nucleosides are salvaged back to nucleoside-triphosphates, with the exception of inosine, whose salvage is limited to IMP. Intracellular balance of nucleosides is maintained by the action of several enzymes, such as adenosine deaminase, uridine phosphorylase and cytidine deaminase, and by at least three 5'-nucleotidases, the ADP activated AMP preferring cN-IA, the ATP-ADP activated IMP-GMP preferring cN-II, and the UMP-CMP preferring cN-III. Here we are reviewing the mechanisms whereby cytosolic 5'-nucleotidases control changes in nucleoside and nucleotide concentration, with the aim to provide a common basis for the study of the relationship between biochemistry and other related disciplines, such as physiology and pharmacology.
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PMID:The functional logic of cytosolic 5'-nucleotidases. 2399 16

Adenine and uracil nucleotides play key functions in the autonomic nervous system (ANS). For instance, ATP acts as a neurotransmitter, co-transmitter and neuromodulator in the ANS. The purinergic system encompasses (1) receptors that respond to extracellular purines, which are designated as P1 and P2 purinoceptors, (2) purine release and uptake, and (3) a cascade of enzymes that regulate the concentration of purines near the cell surface. Ectonucleotidases and adenosine deaminase (ADA) are enzymes responsible for the hydrolysis of ATP (and other nucleotides such as ADP, UTP, UDP, AMP) and adenosine, respectively. Accordingly, these enzymes are expected to play an important role in the control of neuro-effector transmission in tissues innervated by both the sympathetic and parasympathetic divisions of the ANS. Indeed, ectonucleotidases have the ability to either terminate P2 receptor responses initiated by nucleoside triphosphates (ATP and UTP), and/or to favor the activation of ADP (e.g. P2Y1,12,13) and UDP (e.g. P2Y6) and/or adenosine (P1) specific receptors. In addition, ectonucleotidases can also importantly protect some P2 receptors from desensitization (e.g. P2X1, P2Y1). In this review, we present the (putative) roles of ectonucleotidases and ADA in the ANS with a focus on their regulatory activity at neuro-effector junctions in the following tissues: heart, vas deferens, urinary bladder, salivary glands, blood vessels and the intestine. We also present their implication in nociceptive transmission.
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PMID:Impact of ectonucleotidases in autonomic nervous functions. 2600 23


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