Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of a long-term L-DOPA administration (14 days) and 2 weeks after its cessation the activities of some protein enzymes (aminopeptidase, acid phosphatase), neuromediator (MAO, ACE) and oxidative (glutamate dehydrogenase, glucose-6-phosphate dehydrogenase) metabolism were studied by quantitative cytochemical methods in brain motor structures (sensorimotor cortex, caudate nucleus) and in structures not directly related to motor functions (hippocampus) of rats with high and low motor activity. After L-DOPA (madapar) cessation significant changes were revealed in the formation of motor system of the brain, primarily in the group of rats with low motor activity. It is suggested that a decrease in MAO activity after madapar cessation may be responsible for dyskinesia arising after cessation of L-DOPA preparations treatment.
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PMID:[Pathochemical changes in the motor structures of the brain under the influence of the administration of L-DOPA preparations and their withdrawal (experimental research)]. 790 Apr 46

The blood brain barrier (BBB) presents an enzymatic barrier to the passage of peptides, from blood to brain. The studies presented here used a well established in vitro model of the BBB to measure the presence of peptidases and the permeability of two opioid peptides. The in vitro BBB model consisted of confluent monolayers of bovine brain microvessel endothelial cells (BMECs). Enkephalin metabolizing enzymes, total aminopeptidase, aminopeptidase M (APM), angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) activities were measured in BMEC monolayers. The effect of specific inhibitors of APM, ACE and NEP on the permeability of [Met5]enkephalin (Met-Enk) and a conformationally constrained and enzymatically stable analog, DPDPE, also was determined. High levels of membrane-associated enzyme activity were measured for total aminopeptidase, APM and ACE. Interestingly, the permeability coefficient of Met-Enk was increased 4-fold in the presence of specific inhibitors of APM and ACE. Low levels of NEP activity were measured in BMEC monolayers and inhibition of NEP had no effect on Met-Enk permeability. The permeability coefficient for DPDPE was not increased with enzyme inhibitors but was 4-fold greater than Met-Enk alone. In the presence of APM or ACE inhibitors, there was no difference in the permeability of DPDPE and Met-Enk. These experiments demonstrate the presence of specific peptidases in BMECs and that the presence of inhibitors to Met-Enk inactivating peptidases significantly increased permeability of this biologically active peptide.
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PMID:Effect of peptidases at the blood brain barrier on the permeability of enkephalin. 791 19

A scheme based on the zinc binding site [1992, FEBS Lett. 312, 110-114] has been extended to classify zinc metalloproteases into distinct families. The gluzincins, defined by the HEXXH motif and a glutamic acid as the third zinc ligand, include the thermolysin, endopeptidase-24.11, aminopeptidase, angiotensin converting enzyme, endopeptidase-24.15, and tetanus and botulinum neurotoxin families. The metzincins, defined by the HEXXH motif, a histidine as the third zinc ligand and a Met-turn, include the astacin, serralysin, reprolysin and matrixin families. The inverted zincin motif, HXXEH, defines the inverzincin family of insulin-degrading enzymes, the HXXE motif defines the carboxypeptidase family, and the HXH motif DD-carboxypeptidase.
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PMID:Families of zinc metalloproteases. 795 88

Exogenous angiotensin I (ANG I) was degraded to mainly des-Asp-ANG I instead of ANG II in the hypothalamic homogenate of the Sprague Dawley (SD), Wistar Kyoto (WKY), left renal artery stenosed hypertensive SD (LRAS), deoxycorticosterone acetate/salt-induced hypertensive SD (DOCA-salt) and spontaneously hypertensive rats (SHR). In the same homogenate, ANG II was degraded to ANG III and ANG III remained unchanged during the first 10 min of incubation. However, all the homogenates were able to catalyse hippuryl-L-histidyl-L-leucine to hippuric acid and the catalysis was completely inhibited by 3 microM captorpil. The data show that the angiotensin converting enzyme present in the hypothalamus when extracted by the normal laboratory procedures is not able to hydrolyse ANG I to ANG II. In addition, the aminopeptidase that degraded ANG I to des-Asp-ANG I was not inhibited by amastatin, bestatin and EDTA, indicating that it is not aminopeptidase A or B. The formation of hippuric acid was significantly higher in the homogenate of the LRAS whilst the SHR and DOCA-salt showed significant higher rate of des-Asp-ANG I formation than in the normotensive control rats.
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PMID:Formation of des-Asp-angiotensin I in the hypothalamic extract of normo- and hypertensive rats. 799 52

We have isolated a potent inhibitor of enkephalin-degrading enzymes from the bovine spinal cord, and determined its amino-acid sequence and inhibitory activity against enkephalin-degrading enzymes. This new substance, isolated and identified from the bovine spinal cord, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance against enkephalin-degrading enzymes, purified from monkey brain, are 3.3 micrograms.ml-1 against aminopeptidase, 1.4 microgram.ml-1 against dipeptidyl aminopeptidase, 2.4 micrograms.ml-1 against angiotensin converting enzyme, and 10 micrograms.ml-1 against enkephalinase. This new substance showed no inhibitory activity against enkephalin-degrading enzymes purified from kidney, blood, etc. According to the above results, this substance is thought to be a new neuromodulator derived from the spinal cord. Because it was derived from the spinal cord, we have named it "Spinorphin". The discovery in the bovine spinal cord of endogenous heptapeptide, Spinorphin, with inhibitory activity on enkephalin-degrading enzymes raises a number of pertinent questions which cannot be adequately dealt with in this study. It will now be possible, however, to test the very hypothesis that this new peptide act as neurotransmitters or neuromodulators at synaptic junctions.
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PMID:[Spinorphin, a new inhibitor of enkephalin-degrading enzymes derived from the bovine spinal cord]. 823 Jul 3

The inhibitory effects of opioid peptides such as [Met5]-enkephalin and [Met5]-enkephalin-Arg6 on the electrically-evoked contractions of guinea-pig ileum, mouse vas deferens and rat vas deferens were enhanced by aminopeptidase inhibitors such as amastatin and bestatin, a peptidyl dipeptidase A inhibitor like captopril, and endopeptidase-24.11 inhibitors such as phosphoramidon and thiorphan. The magnitude of the enhancement by each peptidase inhibitor depended on both the preparation and opioid peptide employed. Additionally, enkephalin had been shown to be almost exclusively hydrolyzed at least in the ileal and striatal guinea pig membrane preparation by 3 kinds of enzymes, amastatin-sensitive aminopeptidase(s), captopril-sensitive peptidyl dipeptidase A and phosphoramidon-sensitive endopeptidase-24.11, which were indicated to be located very close to opioid receptors.
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PMID:[Enkephalin-inactivating enzymes]. 839 Mar 90

The presence of neutral endopeptidase 24.11 was demonstrated in human umbilical vein endothelial cells by immunostaining. Enzymatic activity of neutral endopeptidase was determined as 0.167 +/- 0.02 mU/mg protein in the membrane fraction of human umbilical vein endothelial cells, using the fluorogenic peptide substrate, dansyl-D-Ala-Gly-Phe(pNO2)-Gly. No activity was found in the cytosolic fraction of endothelial cells. The role of this peptidase in the degradation of the endogenous vasodilator bradykinin was investigated by incubating human umbilical vein endothelial cell monolayers with bradykinin (10(-8) mol/l). The inhibitor of neutral endopeptidase, phosphoramidon (10(-8) mol/l), decreased the degradation of bradykinin in the supernatant of endothelial cells; the half-life of bradykinin was then increased from 29 +/- 1 to 46 +/- 2 minutes. The angiotensin-converting enzyme inhibitor, lisinopril (10(-8) mol/l), increased the half-life of bradykinin to 244 +/- 20 minutes; the combination of both inhibitors increased the half-life of bradykinin to 381 +/- 51 minutes. Inhibitors of aminopeptidase (amastatin) and carboxypeptidase (2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid) caused no significant effect. The effect of phosphoramidon was small in comparison with that of lisinopril, but was pronounced in combination with lisinopril. Neutral endopeptidase activity is localized in the membranes of human endothelial cells and seems to be involved in the degradation of bradykinin by the vascular endothelium, particularly during angiotensin converting enzyme inhibition.
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PMID:Degradation of bradykinin by neutral endopeptidase (EC 3.4.24.11) in cultured human endothelial cells. 839 30

In homogenates of the endothelium and smooth muscle cum adventitia of the rat aorta, exogenous angiotensin (ANG) I was found to be degraded to des-aspartate-ANG I (des-Asp-ANG I) instead of ANG II. ANG II and ANG III were not detectable in either of the homogenates after 5, 10 and 30 min of incubation with the decapeptide. However, both the homogenates were able to catalyse hippuryl-L-histidyl-L-leucine (HHL) to hippuric acid and the catalysis was completely inhibited by 3 microM captopril. The data show that the angiotensin converting enzyme (ACE) present in the homogenates of rat aorta, prepared by normal laboratory procedures, is not able to hydrolyse ANG I to ANG II. This finding has important consequences in the study of vascular ACE as the assay of the enzyme is often carried out using crude homogenate and HHL or other artificial substrates. In addition, the aminopeptidase that degraded ANG I to des-Asp-ANG I was not inhibited by either amastatin or bestatin, indicating that it was not aminopeptidase A or B. Together with the recent findings of other investigators which show that the de novo production of ANG II in vascular tissues is stimulated and inhibited by beta- and alpha-agonists, respectively, our present data may suggest that production of vascular ANG II occurs only in intact tissues and is probably under adrenergic regulation.
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PMID:Degradation of angiotensin I in the endothelium and smooth muscle of the rat aorta. 847 Oct 75

Because of the importance of bradykinin in improving heart function in some conditions or in enhancing glucose uptake by skeletal muscle, we investigated kininases in these tissues. In P3 fraction of the heart and skeletal muscles, angiotensin I-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) are the major kininases, as determined first with specific substrates and second with bradykinin. ACE activity was highest in guinea pig heart (2.7 +/- 0.07 mumol.h-1.mg protein-1) but decreased in other species in this order: dog atrium, rat heart, dog ventricle, and human atrium. The specific activity of NEP was lower: 0.45 mumol.h-1.mg protein-1 in cultured neonatal cardiac myocytes and varying between 0.12 and 0.05 mumol.h-1.mg protein-1 in human, dog, rat, and guinea pig heart. In the skeletal muscle P3, ACE was most active in guinea pig and rat (1.2 and 1.1 mumol.h-1.mg protein-1, respectively) but less so in dog (0.09 mumol.h-1.mg protein-1). NEP activity was higher in dog P3 (0.28 mumol.h-1.mg protein-1) but lower in rat and guinea pig (0.19 and 0.1 mumol.h-1.mg protein-1, respectively). Continuous density gradient centrifugation enriched NEP activity in dog and rat (from 0.3 to 1.0 and 0.49 mumol.h-1.mg protein-1, respectively). Immunoprecipitation with antiserum to purified NEP proved the specificity of the rat enzyme. Bradykinin (0.1 mmol/l) was inactivated in the presence and absence of inhibitors by rat skeletal muscle NEP, as measured by high-performance liquid chromatography. Here, 36% of the activity was caused by NEP and 19% by ACE. In radioimmunoassay (bradykinin 10 nmol/l), 46 and 55% of kininase in rat and dog skeletal muscle P3, respectively, was due to ACE; 36 and 28%, respectively, was due to NEP. Aside from these enzymes, an aminopeptidase in rat P3 also inactivates bradykinin. Thus, in conclusion, heart and skeletal muscle membranes contain kininase II-type enzymes, but their activity depends on the species.
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PMID:Kininase II-type enzymes. Their putative role in muscle energy metabolism. 852 98

Angiotensins (angiotensin I, angiotensin II, angiotensin II-amide) have been isolated in leeches and such peptides are involved in diuresis in these animals. To explore possible inactivation mechanisms of these peptides, angiotensins were incubated with head membranes of the leech T. tessulatum. Membranes derived from head parts of this leech are very rich in peptidases. They contain endopeptidase-24.11-like enzyme (NEP-like) associated with a battery of exopeptidase. The way that angiotensins are degraded by the combined attack of these membrane peptidases has been investigated. The contribution of individual peptidases was assessed by adding inhibitors (phosphoramidon, captopril and amastatin) to the membrane fractions, when they were incubated with the peptides. In the case of angiotensin I, the primary attack was performed by a combined action of the NEP-like and the ACE-like enzymes, followed by aminopeptidase attacks. Angiotensin II and III were hydrolyzed by NEP-like enzyme at the same Tyr-Ile bond, whereas the N-terminal arginine residue of angiotensin III was removed by an arginyl aminopeptidase. These results show that angiotensins are efficiently degraded by membranes and that NEP-like enzyme plays a key role in this process.
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PMID:Metabolism of angiotensins by head membranes of the leech Theromyzon tessulatum. 861 6


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