Diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A): Its role in cellular metabolism

Zamecnik, Paul C.

doi:10.1016/0003-2697(83)90255-5

Cited by 172 publications

(82 citation statements)

References 37 publications

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“…Most aminoacyl-t K N A synthetases, including the isoleucyl-tRNA synthetase from E. coli, are known to produce small amounts of adenosinetetraphosphoadenosine, Ap,A [17]. It has been suggested that after formation of the aminoacyl-adenylate, ATP could replace PPi in the PPi site and react in the reverse reaction with the adenylate to form Ap4A, It is also possible that the /I-phosphately-phosphate interchange reaction in ATP could be connected to a similar binding of ATP to the PPi binding site [18 -201.…”

Section: Discussionmentioning

confidence: 99%

ATP‐induced activation of the aminoacylation of tRNA by the isoleucyl‐tRNA synthetase from Escherichia coli

Airas

1988

European Journal of Biochemistry

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The rate of aminoacylation of tRNA catalyzed by the isoleucyl-tRNA synthetase form Escherichia coli has been measured. A steady-state kinetic analysis of the rate as a function of the concentration of ATP gave nonlinear Hanes plots. ATP behaves as an activator of the reaction. The activation is observed at a low magnesium ion concentration and in the presence of spermidine. The presence of inorganic pyrophosphate or AMP enhances the activation. The results are consistent with a mechanism in which the binding of a second molecule of ATP increases the rate of dissociation of Ile-tRNA from the enyzme.ATP, together with isoleucine and tRNA, is a normal substrate of the isoleucyl-tRNA synthetase: normal Michaelis-Menten kinetics for the formation of isoleucyl-tRNA has been observed over a wide range of ATP concentrations [1, 21. However, there are also some observations of a more complicated role of ATP in the reaction. In a careful steadystate kinetic analysis of the reaction mechanism of the isoleucyl-tRNA synthetase from Escherichia coli, Freist et al.[ 11 suggest an almost random binding of all three substrates and thereafter an apparently random release of the products. However, after the formation of the enzyme-isoleucyladenylate complex, a subsequent binding of a second molecule of ATP was postulated, in order to account for the inhibition patterns by some ATP analogs. Despite the involvement of two molecules of ATP, the double-reciprocal plots were linear (ATP as the variable substrate).Another note about abnormal ATP kinetics by McNeil and Schimmel [3] showed that ATP inhibits the ATP-PPi isotope exchange reaction. It was suggested that ATP could bind to the PPi site after formation of the isoleucyl-adenylate.In the present study we found conditions of low Mg2+ concentration plus spermidine, where the kinetics of dependence of rate on ATP concentration appeared to show activation by ATP. This anomaly is also consistent with a mechanism in which a second ATP molecule is bound to the enzyme, either to a second binding site or to the normal binding site after formation of isoleucyl-adenylate. MATERIALS AND METHODSThe isoleucyl-tRNA synthetase from E. coli

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Section: Discussionmentioning

confidence: 99%

ATP‐induced activation of the aminoacylation of tRNA by the isoleucyl‐tRNA synthetase from Escherichia coli

Airas

1988

European Journal of Biochemistry

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“…In effect, diadenosine polyphosphates (AP.A) have been demonstrated to exist in platelet (Flodgaard & Klenov, 1982;Lutje & Ogilvie, 1983) and in chromaffin granules (Rodriguez del Castillo et al, 1988 (Zamecnik, 1983) 1988). Recently, Louie et al (1988) found an antithrombotic action for AP4A.…”

Section: Introductionmentioning

confidence: 99%

Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells

Castro

Torres

Miras‐Portugal

et al. 1990

British J Pharmacology

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1 The action of several diadenosine polyphosphates (AP3A, AP4A and AP5A) on basal, and on nicotineand high K+-evoked, catecholamine (CA) release has been investigated. Each of the three diadenosine polyphosphates weakly but significantly increased basal CA secretion. This enhancement represented about 10% of the response evoked by 2 J1M nicotine. 2 The evoked secretory response to diadenosine polyphosphates had an absolute requirement for extracellular Ca2".3 In contrast, these compounds had an inhibitory action on nicotine-evoked release. This response was concentration-dependent, EC50 values being 3.2 + 0.4OAM, 4.0 + 1.6./M and 19.3 + 4.0/AM for AP A AP4A, and AP5A, respectively. The lower the concentration of nicotine used to evoke secretion, the higher the inhibitory power of these compounds.4 The CA secretion evoked by K+-rich solutions was further enhanced by AP3A and APA, whereas AP4A inhibited it. The possible physiological role of these dual actions is discussed.

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“…Contrary to Ap4 A, Ap3A is not a strong chelator of Me 2÷, and consequently does not affect the aminoacylation function of TrpRS. Ap3A is often regarded as physiological antagonist of Ap4A (see [3,19] and references therein). We assume that Ap4A-synthesyzing (Lys, Pro, etc.)…”

Section: Discussionmentioning

confidence: 99%

“…The ability to catalyze ApnA and Ap3A synthesis was first reported for lysyl-tRNA synthetase from E. coli [5]. Later some other aaRS of different origin and amino acid specificity were shown to synthesize such dinucleoside oligophosphates in vitro (see [3]). It was suggested that these aaRS are also able to catalyze in vivo Ap4A and Ap3A synthesis.…”

Section: Introductionmentioning

confidence: 95%

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P¹, P³‐bis(5′‐adenosyl)triphosphate (Ap₃A) as a substrate and a product of mammalian tryptophanyl‐tRNA synthetase

1994

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Bovine tryptophanyl-tRNA synthetase (TrpRS, E.C. 6.1.1.2) is unable to catalyze in vitro formation of Ap4A in contrast to some other aminoacyltRNA synthetases. However, in the presence of L-tryptophan, ATP-Mg 2÷ and ADP the enzyme catalyzes the Ap3A synthesis via adenylate intermediate. Ap3A (not Ap4A) may serve as a substrate for TrpRS in the reaction of E. (Trp ~ AMP) formation and in the tRNA Tw charging. The Km value for Ap3A was higher than the Km for ATP (approx. 1.00 vs. 0.22 mM) and Vm~x was 3 times lower than for ATP. The Zn2+-deficient enzyme catalyzes Ap3A synthesis in the absence of exogenous ADP due to ATPase activity of Zn2+-deprived TrpRS. The inability of mammalian TrpRS to synthesize Ap4A, might be considered as a molecular tool preventing the removal of Zn 2÷ due to chelation by Ap4A and therefore preserving the enzyme activity.

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Diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A): Its role in cellular metabolism

Cited by 172 publications

References 37 publications

ATP‐induced activation of the aminoacylation of tRNA by the isoleucyl‐tRNA synthetase from Escherichia coli

ATP‐induced activation of the aminoacylation of tRNA by the isoleucyl‐tRNA synthetase from Escherichia coli

Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells

P¹, P³‐bis(5′‐adenosyl)triphosphate (Ap₃A) as a substrate and a product of mammalian tryptophanyl‐tRNA synthetase

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Diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A): Its role in cellular metabolism

Cited by 172 publications

References 37 publications

ATP‐induced activation of the aminoacylation of tRNA by the isoleucyl‐tRNA synthetase from Escherichia coli

ATP‐induced activation of the aminoacylation of tRNA by the isoleucyl‐tRNA synthetase from Escherichia coli

Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells

P1, P3‐bis(5′‐adenosyl)triphosphate (Ap3A) as a substrate and a product of mammalian tryptophanyl‐tRNA synthetase

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P¹, P³‐bis(5′‐adenosyl)triphosphate (Ap₃A) as a substrate and a product of mammalian tryptophanyl‐tRNA synthetase