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Chemical Compound Review:

AppppppA [(2R,3S,4R,5R)-5-(6- aminopurin-9-yl)-3,4...

Synonyms: Ap6A, CHEBI:63689, HMDB01282, KST-1A6247, LS-15142, ...

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Diadenosine hexaphosphate

The Nudix hydrolase Ndx1 from Thermus thermophilus HB8 is a diadenosine hexaphosphate hydrolase with a novel activity [1].
The synthesis of diadenosine hexaphosphate (Ap6A), a potent vasoconstrictor, is catalyzed by acyl-CoA synthetase from Pseudomonas fragi [2].

High impact information on Diadenosine hexaphosphate

Here we isolate these vasopressors and identify them as diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) by chromatography, mass spectrometry, ultraviolet spectroscopy and enzymatic cleavage [3].
Diadenosine hexaphosphate (Ap(6)A), the most preferred substrate, was hydrolyzed to produce two ATP molecules, which is a novel hydrolysis mode for Ap(6)A, with a K(m) of 1.4 microm and a k(cat) of 4.1 s(-1) [1].
Diphosphoinositol polyphosphate phosphohydrolase (DIPP) hydrolyzes diadenosine 5',5"'-P(1),P(6)-hexaphosphate (Ap(6)A), a Nudix (nucleoside diphosphate attached-moiety "x") substrate, and two non-Nudix compounds: diphosphoinositol pentakisphosphate (PP-InsP(5)) and bis-diphosphoinositol tetrakisphosphate ((PP)(2)-InsP(4)) [4].
Mutagenesis of either of two conserved glutamate residues (Glu(66) and Glu(70)) within the Nudt (Nudix-type) catalytic motif impaired hydrolysis of Ap(6)A, PP-InsP(5), and (PP)(2)-InsP(4) >95%; thus, all three substrates are hydrolyzed at the same active site [4].
Identification of diadenosine hexaphosphate in human erythrocytes [5].

Biological context of Diadenosine hexaphosphate

The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein [6].

Anatomical context of Diadenosine hexaphosphate

OBJECTIVE: To evaluate the effects of two new endogenous vasoconstricting substances, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) on the cytosolic free calcium concentration in vascular smooth muscle cells [7].
Characterization and quantification of diadenosine hexaphosphate in chromaffin cells: granular storage and secretagogue-induced release [8].
Ap(5)A, Ap(5)G, Ap(6)A and Ap(6)G are vasodilating or vasoconstricting nucleotides that activate P2Y(1) or P2X receptors depending on the status of the coronary vascular endothelium [9].
The responses of human isolated umbilical artery to the novel platelet-derived mediators, diadenosine phosphates, P1,P5-di(adenosine-5')pentaphosphate (AP5A) and P1,P6-di(adenosine-5')hexaphosphate (AP6A) were studied in vitro [10].
Ap(4)A, Ap(5)A, and Ap(6)A are stored together with other neurotransmitters into secretory vesicles and are co-released to the extracellular medium upon stimulation [11].

Gene context of Diadenosine hexaphosphate

More distal to the Nudt motif, H91L and F84Y mutations substantially decreased the rate of Ap(6)A and (PP)(2)-InsP(4) metabolism (by 71 and 96%), yet PP-InsP(5) hydrolysis was only mildly reduced (by 30%); these results indicate substrate-specific roles for His(91) and Phe(84) [4].
Disruption of aps1 resulted in a 52% decrease in Ap(6)A hydrolase activity in vitro, no detectable change in the intracellular Ap(5)A concentration, and 3-fold increased intracellular concentrations of PP-Ins P(5) and [PP](x)-InsP(x) [12].

Analytical, diagnostic and therapeutic context of Diadenosine hexaphosphate

In one of the purified fractions, diadenosine hexaphosphate (diadenosine 5', 5'-P(1), P(6) hexaphosphate [AP(6)A]) was identified by matrix-assisted laser desorption/ionization mass spectrometry, ultraviolet spectroscopy, and enzymatic analysis [5].

References

The Nudix hydrolase Ndx1 from Thermus thermophilus HB8 is a diadenosine hexaphosphate hydrolase with a novel activity. Iwai, T., Kuramitsu, S., Masui, R. J. Biol. Chem. (2004) [Pubmed]
Acyl-CoA synthetase catalyzes the synthesis of diadenosine hexaphosphate (Ap6A). Fontes, R., Günther Sillero, M.A., Sillero, A. Biochimie (1999) [Pubmed]
Diadenosine phosphates and the physiological control of blood pressure. Schlüter, H., Offers, E., Brüggemann, G., van der Giet, M., Tepel, M., Nordhoff, E., Karas, M., Spieker, C., Witzel, H., Zidek, W. Nature (1994) [Pubmed]
Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphates. Yang, X., Safrany, S.T., Shears, S.B. J. Biol. Chem. (1999) [Pubmed]
Identification of diadenosine hexaphosphate in human erythrocytes. Luo, J., Jankowski, J., Tepel, M., von Der Giet, M., Zidek, W., Schlüter, H. Hypertension (1999) [Pubmed]
The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein. Safrany, S.T., Ingram, S.W., Cartwright, J.L., Falck, J.R., McLennan, A.G., Barnes, L.D., Shears, S.B. J. Biol. Chem. (1999) [Pubmed]
Diadenosine polyphosphate-induced increase in cytosolic free calcium in vascular smooth muscle cells. Tepel, M., Bachmann, J., Schluter, H., Zidek, W. J. Hypertens. (1995) [Pubmed]
Characterization and quantification of diadenosine hexaphosphate in chromaffin cells: granular storage and secretagogue-induced release. Pintor, J., Rotllán, P., Torres, M., Miras-Portugal, M.T. Anal. Biochem. (1992) [Pubmed]
Effects of dinucleoside polyphosphates on regulation of coronary vascular tone. van der Giet, M., Schmidt, S., Tölle, M., Jankowski, J., Schlüter, H., Zidek, W., Tepel, M. Eur. J. Pharmacol. (2002) [Pubmed]
Effect of diadenosine phosphates on human umbilical vessels: novel platelet-derived vasoconstrictors. Davies, G., MacAllister, R.J., Bogle, R.G., Vallance, P. British journal of clinical pharmacology. (1995) [Pubmed]
Dinucleoside polyphosphates and their interaction with other nucleotide signaling pathways. Delicado, E.G., Miras-Portugal, M.T., Carrasquero, L.M., León, D., Pérez-Sen, R., Gualix, J. Pflugers Arch. (2006) [Pubmed]
Disruption and overexpression of the Schizosaccharomyces pombe aps1 gene, and effects on growth rate, morphology and intracellular diadenosine 5',5"'-P1,P5-pentaphosphate and diphosphoinositol polyphosphate concentrations. Ingram, S.W., Safrany, S.T., Barnes, L.D. Biochem. J. (2003) [Pubmed]

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