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Gene Review

Apeh  -  acylaminoacyl-peptide hydrolase

Rattus norvegicus

Synonyms: AARE, APH, Acyl-peptide hydrolase, Acylamino-acid-releasing enzyme, Acylaminoacyl-peptidase
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Disease relevance of Apeh


High impact information on Apeh


Chemical compound and disease context of Apeh


Biological context of Apeh

  • We also suggest that, by comparison of structure-activity relationships, acylpeptide hydrolase may be the target for the cognitive-enhancing effects of certain organophosphorus compounds [9].
  • If the active D-isomer of APH (10 microM) or DL-APV (50 microM), but not if L-APH was present during tetanization, both EPSP and spike potentiation were markedly reduced or even blocked for the whole recording period (8 h after tetanization) [10].
  • Under control (non-TTX) conditions, neither DNQX nor APH showed significant effects on 10 mM potassium-induced cell death, indicating that stimulation of the non-NMDA, as well as the NMDA receptors is neurotoxic [11].
  • The deduced amino acid sequence encoded a 764 amino acid protein of 83.9 kDa, which was 31.8% identical with that of rat AARE [4].
  • D,L-2-amino-7-phosphonoheptanoic acid (APH) dose-dependently inhibited NMDA effect (IC50 = 69 mumol/L), whereas at 1 mmol/L it was ineffective versus kainic acid [12].

Anatomical context of Apeh


Associations of Apeh with chemical compounds

  • Acyl-peptide hydrolase appears to be a serine protease utilizing a charge relay system involving serine, histidine, and, probably, a carboxyl group(s) [7].
  • NMDA blockade was achieved by injection of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate [MK-801; 3 and 10 mg/kg] or amino-7-phosphonoheptanoate (APH; 4.5 and 10 mg/kg) [16].
  • Furthermore, using dichlorvos as a progressive inhibitor, it was possible to show that acylpeptide hydrolase is the only enzyme in the brain capable of hydrolyzing the substrate N-acetyl-alanyl-p-nitroanilide [9].
  • Acylpeptide hydrolase was found to be potently inhibited by the organophosphorus compounds chlorpyrifosmethyl oxon, dichlorvos, and diisopropylfluorophosphate (20-min IC(50) values of 18.3 +/- 2.0, 118.7 +/- 9.7, and 22.5 +/- 1.2 nM, respectively) [9].
  • To investigate the preferred spatial relationship of the distal phosphonic acid to the alpha-amino acid group of the established competitive N-methyl-D-aspartic acid (NMDA) antagonists APH (1) and APV (2), we have prepared a series of ortho-, meta-, and para-substituted (phosphonoalkyl)phenylglycine and -phenylalanine derivatives [17].

Other interactions of Apeh


Analytical, diagnostic and therapeutic context of Apeh

  • Cloning and sequence analysis of a rat liver cDNA encoding acyl-peptide hydrolase [6].
  • The target, acylpeptide hydrolase, was isolated as a tritiated-diisopropylfluorophosphate-reactive protein from porcine brain and purified to homogeneity using a combination of ion-exchange and gel-filtration chromatography [9].
  • In experiment 3, microinjection of the ineffective 0.1 microgram dose of APH or a dose (20 micrograms) of the DA antagonist, cis-flupenthixol, that did not produce circling when administered alone, significantly reduced the circling response produced by the 5.0 micrograms dose of NMDA [19].
  • Perfusion of the acidic amino acid antagonists, DL-2-amino-5-phosphonovalerate (APV), 10(-6) or 10(-5) M, DL-2-amino-7-phosphonoheptanoate (APH), 10(-5) M, and gamma-D-glutamylglycine (gamma DGG), 10(-5) M, selectively blocked the response to NMDA without effect on the response to aspartate [20].
  • The anticonvulsant action of APH along the extent of the PC is localised in the vicinity of the injection site, as shown by autoradiography following focal injection of tritiated APH [21].


  1. The gene from the short arm of chromosome 3, at D3F15S2, frequently deleted in renal cell carcinoma, encodes acylpeptide hydrolase. Erlandsson, R., Boldog, F., Persson, B., Zabarovsky, E.R., Allikmets, R.L., Sümegi, J., Klein, G., Jörnvall, H. Oncogene (1991) [Pubmed]
  2. Continuously infused 2-amino-7-phosphonoheptanoic acid antagonizes N-methyl-D-aspartate-induced elevations of cyclic GMP in vivo in multiple brain areas and chemically-induced seizure activity. McCaslin, P.P., Morgan, W.W. Neuropharmacology (1986) [Pubmed]
  3. Effect of NMDA and 2-amino-7-phosphonoheptanoate focal injection into the ventrolateral thalamic nucleus on the high pressure neurological syndrome in the rat. Millan, M.H., Wardley-Smith, B., Halsey, M.J., Meldrum, B.S. Brain Res. (1990) [Pubmed]
  4. Identification and biochemical characterization of plant acylamino acid-releasing enzyme. Yamauchi, Y., Ejiri, Y., Toyoda, Y., Tanaka, K. J. Biochem. (2003) [Pubmed]
  5. The characterization of the specific binding of [3H]-N-acetylaspartylglutamate to rat brain membranes. Koller, K.J., Coyle, J.T. J. Neurosci. (1985) [Pubmed]
  6. Cloning and sequence analysis of a rat liver cDNA encoding acyl-peptide hydrolase. Kobayashi, K., Lin, L.W., Yeadon, J.E., Klickstein, L.B., Smith, J.A. J. Biol. Chem. (1989) [Pubmed]
  7. Acyl-peptide hydrolase from rat liver. Characterization of enzyme reaction. Kobayashi, K., Smith, J.A. J. Biol. Chem. (1987) [Pubmed]
  8. Intraventricular infusion of 2-amino-7-phosphonoheptanoate (APH) mitigates ischaemic brain damage. Jensen, M.L., Auer, R.N. Neurol. Res. (1989) [Pubmed]
  9. Identification of acylpeptide hydrolase as a sensitive site for reaction with organophosphorus compounds and a potential target for cognitive enhancing drugs. Richards, P.G., Johnson, M.K., Ray, D.E. Mol. Pharmacol. (2000) [Pubmed]
  10. N-methyl-D-aspartate receptor activation is required for the induction of both early and late phases of long-term potentiation in rat hippocampal slices. Reymann, K.G., Matthies, H.K., Schulzeck, K., Matthies, H. Neurosci. Lett. (1989) [Pubmed]
  11. The effects of potassium-induced depolarization, glutamate receptor antagonists and N-methyl-D-aspartate on neuronal survival in cultured neocortex explants. Ruijter, J.M., Baker, R.E. Int. J. Dev. Neurosci. (1990) [Pubmed]
  12. Stimulation of [3H]norepinephrine release from hippocampal slices by excitatory amino acids. Wu, H.Q., Vezzani, A., Samanin, R. Zhongguo yao li xue bao = Acta pharmacologica Sinica. (1989) [Pubmed]
  13. Decrease in excitatory transmission within the lateral habenula and the mediodorsal thalamus protects against limbic seizures in rats. Patel, S., Millan, M.H., Meldrum, B.S. Exp. Neurol. (1988) [Pubmed]
  14. Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. McMaster, O.G., Du, F., French, E.D., Schwarcz, R. Exp. Neurol. (1991) [Pubmed]
  15. Studies on the role of the NMDA receptor in the substantia nigra pars reticulata and entopeduncular nucleus in the development of the high pressure neurological syndrome in rats. Millan, M.H., Wardley-Smith, B., Halsey, M.J., Meldrum, B.S. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1989) [Pubmed]
  16. The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. Lauritzen, M., Hansen, A.J. J. Cereb. Blood Flow Metab. (1992) [Pubmed]
  17. Exploration of phenyl-spaced 2-amino-(5-9)-phosphonoalkanoic acids as competitive N-methyl-D-aspartic acid antagonists. Bigge, C.F., Drummond, J.T., Johnson, G., Malone, T., Probert, A.W., Marcoux, F.W., Coughenour, L.L., Brahce, L.J. J. Med. Chem. (1989) [Pubmed]
  18. The peptide sequences near the bound pyridoxal phosphate are conserved in serine dehydratase from rat liver, and threonine dehydratases from yeast and Escherichia coli. Ogawa, H., Konishi, K., Fujioka, M. Biochim. Biophys. Acta (1989) [Pubmed]
  19. N-methyl-D-aspartate unilaterally injected into the dorsal striatum of rats produces contralateral circling: antagonism by 2-amino-7-phosphonoheptanoic acid and cis-flupenthixol. Thanos, P.K., Jhamandas, K., Beninger, R.J. Brain Res. (1992) [Pubmed]
  20. N-Methyl-D-aspartate and L-aspartate activate distinct receptors in piriform cortex. ffrench-Mullen, J.M., Hori, N., Carpenter, D.O. Cell. Mol. Neurobiol. (1984) [Pubmed]
  21. Focal injection of 2-amino-7-phosphonoheptanoic acid into prepiriform cortex protects against pilocarpine-induced limbic seizures in rats. Millan, M.H., Patel, S., Mello, L.M., Meldrum, B.S. Neurosci. Lett. (1986) [Pubmed]
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