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)

Dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) and post proline cleaving enzyme (PPCE; EC 3.4.21.26) can convert or degrade vasoactive peptides and have been identified in isolated vessels. The present study examined the cellular (endothelial/smooth muscle) localization of vascular DAP IV and PPCE. Membrane-bound DAP IV was higher on cultured hog aorta smooth muscle (11.7 +/- 1.7 nmol/min/mg) than on endothelium (1.5 +/- 0.3 nmol/min/mg). In contrast, comparable levels of cytosolic PPCE were found in endothelium and smooth muscle (1.5 +/- 0.3 and 1.8 +/- 0.3 nmol/min/mg, respectively). DAP IV was specifically inhibited by diprotin A (Ile-Pro-Ile) (IC50 = 6 microM) while PPCE was inhibited by TPCK. Neither enzyme was affected by o-phenanthroline or inhibitors of aminopeptidase M (amastatin, bestatin), neutral endopeptidases (phosphoramidon), carboxypeptidases N (MERGETPA) or ACE (captopril). DAP IV may play a role in the extracellular metabolism of peptides at or near endothelial and smooth muscle cell surface receptors. In contrast, the cytosolic localization of PPCE may limit its participation to intracellular peptide metabolism.
 ...
PMID:Dipeptidyl(amino)peptidase IV and post proline cleaving enzyme in cultured endothelial and smooth muscle cells. 257 34

Angiotensin converting enzyme (EC 3.4.15.1, dipeptidyl carboxypeptidase, ACE, Kininase II), the peptidase which transforms inactive decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and which catalyses also the degradation of vasodilative nonapeptide bradykinin, was measured in 27 human tissue homogenates and physiological fluids. Two assays were used: one which measures the hydrolysis of the substrate hippuryl-glycyl-glycine, by means of high performance liquid chromatography and another, using a colorimetric assay measuring the cleaved glycyl-glycine after arylation with picrylsulfonic acid. All the tissues studied contained measurable converting enzyme activities which were inhibited by captopril (SQ 14.225) in low concentrations. High specific activities of converting enzyme were found in several tissues of the intestinal and urogenital tract, but the highest activity was found in benign prostatic hyperplasia. Normal prostate and prostatic adenocarcinoma have a much lower activity. Results obtained for human tissues are compared with those found in animals.
 ...
PMID:Distribution of angiotensin converting enzyme in human tissues. 258 25

Bradykinin (BK) (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) was degraded by rat brain synaptic membranes at a rate comparable to that found for Met-enkephalin, but approximately 40 times the rate for vasopressin and oxytocin. The catabolic pathway for BK and its metabolites was elucidated through the use of high performance liquid chromatography for metabolite identification and peptidase inhibitors for blocking specific cleavage sites. BK was hydrolyzed at three sites: at the -Phe5-Ser6- bond by metalloendopeptidase 24.15, at the -Pro7-Phe8- bond by an apparently novel peptidyl dipeptidase, and at the -Phe8-Arg9 bond by a carboxypeptidase B-like enzyme. Each enzyme contributed about equally to BK degradation under the assay conditions used. Some of the resulting metabolites were further hydrolyzed: BK(1-8) to BK(1-7) + Phe by a DFP inhibitable prolyl carboxypeptidase-like enzyme, BK(1-8) to BK(1-5) + BK(6-8) by metalloendopeptidase 24.15, BK(1-7) slowly to BK(1-5) by a second peptidyl dipeptidase which was captopril inhibited, and Phe-Arg to Phe + Arg by a bestatin-inhibited dipeptidase. A number of properties of the individual enzymes were determined including sensitivity to a variety of peptidase inhibitors. These results provide a starting point for investigating the potential physiological role of each enzyme in BK function in the brain.
 ...
PMID:Degradation of bradykinin and its metabolites by rat brain synaptic membranes. 260 54

The relative importance of three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A and phosphoramidon-sensitive endopeptidase-24.11, to inactivate two opioid peptides, [Met5]-enkephalin and [Met5]-enkephalin-Arg6, was investigated in three in vitro isolated preparations, guinea-pig ileum, mouse vas deferens and rat vas deferens, by estimating the magnitude of the enhancement of the inhibitory potency of the opioid peptide by each peptidase inhibitor. Results showed that the relative importance of the three enzymes in the inactivation of the opioid peptide, whether it was [Met5]-enkephalin or [Met5]-enkephalin-Arg6, in guinea-pig ileum was significantly different from that in either mouse vas deferens or rat vas deferens. Additionally, the relative importance of the three enzymes in the preparation, whether it was guinea-pig ileum, mouse vas deferens or rat vas deferens, in the inactivation of [Met5]-enkephalin was significantly different from that of [Met5]-enkephalin-Arg6. The significance of the presence of plural inactivating-enzymes for opioid peptides was discussed.
 ...
PMID:Estimation of relative importance of three enzymes in the inactivation of [Met5]-enkephalin and [Met5]-enkephalin-Arg6 in three isolated preparations by employing the inhibitor specific for each enzyme. 282 6

1. The effects of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on plasma vasoactive intestinal polypeptides (VIP) and plasma noradrenaline, adrenaline and dopamine were studied in 12 patients with congestive heart failure over two consecutive 48-hr periods. The first day in each period served as a treatment day and the second as a control day. 2. A parallel monitoring was made of various hormonal parameters related to the renin-angiotensin-aldosterone system, and a right-heart catheter was used to monitor haemodynamics at rest. 3. Potent inhibition of the renin-system (as demonstrated by decreases in angiotensin converting enzyme (ACE) activity, angiotensin II and plasma aldosterone) together with improved haemodynamics (decreases in mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure and mean systemic arterial pressure) were recorded. 4. Plasma VIP was significantly increased by a mean of 20.3% (P less than 0.01) on the lisinopril treatment days compared with the control days, whereas circulating catecholamines showed no significant pattern of change. 5. It is postulated that the potent vasodilatory neuromodulator VIP is implicated in the ACE inhibitor effects. 6. The ACE is a non-specific peptidase that previously has been implicated in the potentiation of other vasoactive endogenous systems (kinins and enkephalins).
 ...
PMID:Increase in vasoactive intestinal polypeptides (VIP) by the angiotensin converting enzyme (ACE) inhibitor lisinopril in congestive heart failure. Relation to haemodynamic and hormonal changes. 282 21

The role of rat intestinal angiotensin-converting enzyme (ACE; E.C 3.4.15.1) in the digestion and absorption of dietary protein was investigated. Enzyme activity was associated with the brush-border membrane fraction, with the highest activity in the proximal to midregion of the small intestine. Preliminary enzyme characterization studies were carried out using purified brush-border membrane preparations. When a variety of N-blocked synthetic peptides were used as potential substrates for ACE, activity was highest with those containing proline at the carboxy terminal position. The hydrolytic rates observed with these prolyl peptides were comparable to those observed when major digestive peptidases of the brush-border membrane such as aminopeptidase N and dipeptidyl aminopeptidase IV were assayed. When isolated rat jejunum was perfused in vivo with solutions of Bz-Gly-Ala-Pro, the dipeptide Ala-Pro was the main hydrolytic product detected in the perfusates. Absorption rates of the constituent amino acids, alanine and proline, depended on the concentration of peptide perfused. Captopril, an active site specific ACE inhibitor, significantly inhibited hydrolysis and absorption of constituent amino acids from Bz-Gly-Ala-Pro. These results show that intestinal brush-border membrane ACE functions as a digestive peptidase in addition to its role as a regulator of biologically active peptides in other tissues.
 ...
PMID:Role of rat intestinal brush-border membrane angiotensin-converting enzyme in dietary protein digestion. 282 4

We have investigated the effect of amastatin, an aminopeptidase inhibitor, and captopril, an angiotensin converting enzyme inhibitor, on the antinociceptive activity induced by intracerebroventricular administration of dermorphin, a heptapeptide. In addition, the potency of dermorphin was compared with that of one of its metabolites, N-terminal tetrapeptide (Tyr-D-Ala-Phe-Gly), by using the tail pressure test. The antinociceptive activity induced by dermorphin was not potentiated by simultaneous administration of amastatin or captopril. However, there was potentiation when dermorphin was combined with both peptidase inhibitors. Moreover, the N-terminal tetrapeptide was 84 times less potent than its parent heptapeptide when administered intracerebroventricularly. The results suggest that the cleavage of Tyr1-D-Ala2 and Gly4-Tyr5 bonds by brain endopeptidase modulates dermorphin-induced antinociceptive activity.
 ...
PMID:Potentiation of dermorphin-induced antinociception by peptidase inhibitors. 287 Nov 64

Based on differences in total metabolite accumulation in the presence or absence of selective peptidase inhibitors, rat plasma is found to have its own unique pattern of enkephalin hydrolysis. Approximately 85-90% of the hydrolysis of [leu]enkephalin is attributed to the combined action of aminopeptidase M and angiotensin converting enzyme, whereas "enkephalinase" and aminopeptidase MII activity against [leu]enkephalin are not detectable. Similarly, 80-90% of the hydrolysis of D-ala2-[L-leu] enkephalin (DALLE) is due to the combined action of aminopeptidase M and angiotensin converting enzyme, whereas aminopeptidase MII and enkephalinase activity against this substrate also could not be detected. This is in contrast to the high susceptibility to hydrolysis by enkephalinase, and the low susceptibility to aminopeptidase activity, for DALLE in brain tissue. Among other alternatives, it is suggested that enkephalin hydrolysis in plasma may appear to be unique because of differences in enzyme conformation and/or the availability of a substance(s) that competes with, or alters the binding of, [leu] enkephalin, DALLE or the inhibitors to the enzymes.
 ...
PMID:Characterization of hydrolysis of [leu]enkephalin and D-ala2-[L-leu]enkephalin in rat plasma. 290 10

Atrial natriuretic peptide is rapidly degraded by a soluble, heat labile peptidase isolated from ventricular myocytes. Degradation of [125I]-ANP is antagonized by unlabelled ANP, bradykinin, glucagon, 1,10-phenanthroline, PCMB, EDTA and the bacterial antibiotic bacitracin, but not by phenylmethylsulphonyl fluoride, aprotinin, phosphoramidon, E-64, amastatin or the ACE inhibitor SQ 20881 and bradykinin potentiator C. In addition neither bovine serum albumin nor caesin afforded any protection against degradation. Peptidase activity was optimal at pH values above 8.5. The peptidase is likely to be of intracellular origin and may contribute to the extensive ANP degradative activity found in various ventricular muscle preparations.
 ...
PMID:Degradation of [125I]-atrial natriuretic peptide by a soluble metallopeptidase isolated from rat ventricular myocytes. 296 71

Two pentapeptide analogues of the ketomethylene-containing angiotensin converting enzyme (ACE) inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and evaluated as ACE inhibitors and antihypertensive agents. Compounds 14 and 15 were very potent ACE inhibitors with I50 values of 7.0 and 3.0 nM, respectively, compared to an I50 value of 70 nM for 1. Neither 14 nor 15 showed significant blood pressure lowering activity in renal hypertensive rats. Investigations conducted on a tritiated analogue of 14 showed that 70% of an oral dose of this compound is absorbed but is rapidly excreted from the blood with a half life of 24 min. Thin-layer chromatography of bile and urine contents in rats given tritiated 14 orally showed that it is excreted in greater than 90% unchanged form. This implies that a ketomethylene linkage can stabilize peptide amide linkages adjacent to it to peptidase degradation.
 ...
PMID:Synthesis and biological activity of pentapeptide analogues of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline. 299 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>