Disease relevance of Apeh

• The renal cell carcinoma is then associated with a decrease of acylpeptide hydrolase activity [1].
• Doses of APH ranging from 2.7 to 54 micrograms/day were examined for signs of toxicity [2].
• We report the effect of focal injections of N-methyl-D-aspartate (NMDA, 5 nmol) and 2-amino-7-phosphonoheptanoate (APH, 5 and 10 nmol) into the ventrolateral thalamic nucleus on behavioural symptoms of the high pressure neurological syndrome in rats [3].
• APH, 10 nmol, significantly increases the threshold pressure for myoclonus and convulsions [3].
• Recombinant AtAARE was expressed in Escherichia coli and confirmed to be a functional AARE [4].

High impact information on Apeh

• [3H]NAAG specific binding was displaceable by serine-o-sulfate, quisqualate, ibotenate, and glutamate with K1's in the nanomolar range, whereas the amino-phosphono analogues displaced [3H] NAAG in the micromolar range (APB greater than APV greater than APH) [5].
• This result suggests that acyl-peptide hydrolase may be a unique serine protease [6].
• This clone contained 2364 base pairs of rat acyl-peptide hydrolase sequence but lacked a translational initiation codon [6].
• Two overlapping degenerate oligonucleotide probes based on the sequence of a CNBr tryptic peptide, derived from purified rat acyl-peptide hydrolase, were synthesized and used to screen a rat liver lambda gt11 cDNA library [6].
• Acyl-peptide hydrolase, which catalyzes the hydrolysis of an N-terminally acetylated peptide to release an N-acetylamino acid, was isolated from rat liver and found to be N-terminally blocked [7].

Chemical compound and disease context of Apeh

• The highest tolerable concentration of APH, 50 mM, was given at 1 microliter/h. Selective neuronal necrosis was significantly reduced in the cerebral cortex and the incidence of infarction in the substantia nigra pars reticulata (SNPR) was decreased [8].

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

• The dose of APH required to give sustained protection against pilocarpine-induced convulsions is 10 pmol for lateral habenula and 50 pmol for mediodorsal thalamus [13].
• The excitatory amino acid antagonist 2-amino-7-phosphonoheptanoate (APH, selective for the NMDA preferring glutamate receptor subtype) is potently anticonvulsant after bilateral focal injections into the habenula or mediodorsal thalamus [13].
• Co-injection of 225 nmol APH completely protected the hippocampus from AOAA-induced damage [14].
• The effect of the focal injection of N-methyl-D-aspartate (NMDA) and 2-amino-7-phosphonoheptanoate (APH) into the substantia nigra pars reticulata (SNR) and entopeduncular nucleus (EP) on behavioural signs of the high pressure neurological syndrome (HPNS) in rats was studied [15].
• These protective effects are, however, less pronounced than those produced by either systemic injection of APH or its focal infusion into the basal ganglia output system [3].

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

• The blocked amino-terminal residue of rat liver serine dehydratase was shown to be acetylalanine by analysis of an isolated amino-terminal peptide after digestion with acylamino acid-releasing enzyme [18].
• The gene from the short arm of chromosome 3, at D3F15S2, frequently deleted in renal cell carcinoma, encodes acylpeptide hydrolase [1].

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].

References