Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bradykinin is susceptible to degradation by a variety of endo- and exopeptidases. These include aminopeptidase P, meprin, endopeptidase 24.15, prolyl endopeptidase, neutral endopeptidase 24.11, angiotensin I-converting enzyme, carboxypeptidase N, carboxypeptidase M, and deamidase. These peptidases are widely distributed in various tissues and cells in the body, and their subcellular locations vary as well. Because bradykinin is inactivated (for binding the B2 receptor) when any of its peptide bonds are cleaved, all of these enzymes qualify as potential "kininases" in vivo; however, the importance of a particular enzyme as a kininase will depend on its localization, access to bradykinin, and the presence of other peptidases. In addition, these peptidases can cleave a variety of other peptide hormone substrates. Determination of the importance of a peptidase in the inactivation of bradykinin during a particular physiological response can be difficult, but specific peptidase inhibitors and kinin receptor antagonists are useful tools in investigating these questions.
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PMID:Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology. 128 29

The expression of cell-surface peptidases was examined in two human colon carcinoma cell lines, Caco-2 and HT-29. Enzymic assays revealed the presence of eight cell-surface peptidases on a Caco-2 cell line (passage number 82-88), namely aminopeptidase N, dipeptidyl peptidase IV, peptidyl dipeptidase A (angiotension-converting enzyme), aminopeptidase P, aminopeptidase W, endopeptidase-24.11, gamma-glutamyl transpeptidase and membrane dipeptidase. The presence of dipeptidyl peptidase IV and endopeptidase-24.11 was also confirmed immunochemically. After 15 days culture, the activities of aminopeptidase P, peptidyl dipeptidase A and alkaline phosphatase activities on Caco-2 cells reached a plateau, and that of membrane dipeptidase began to decline. In contrast, aminopeptidase N, dipeptidyl peptidase IV and endopeptidase-24.11 activities were still rising after 26 days in culture. Caco-2 cells of passage number 181-183 were found to lack endopeptidase-24.11, but maintained dipeptidyl peptidase IV expression. Two populations of HT-29 cells were surveyed. Both the standard, undifferentiated population and a differentiated population expressed only three peptidases: dipeptidyl peptidase IV, aminopeptidase W and carboxypeptidase M. In the differentiated HT-29 cells the activity of dipeptidyl peptidase IV after 14-21 days was beginning to plateau whereas aminopeptidase W activity was still rising and that of carboxypeptidase M had begun to decline. These differences in activity profiles observed among this group of cell-surface peptidases indicate that these cell lines, especially Caco-2, are useful models to study the regulation of their expression.
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PMID:A survey of membrane peptidases in two human colonic cell lines, Caco-2 and HT-29. 131 37

In addition to angiotensin I converting enzyme (ACE; EC 3.4.15.1) and carboxypeptidase N (CPN; EC 3.4.17.3), other peptidases contribute to bradykinin (BK) degradation in plasma. Rat plasma degraded BK by hydrolysis of the N-terminal Arg1-Pro2 bond, and the characteristics of hydrolysis are consistent with identification of aminopeptidase P (APP; EC 3.4.11.9) as the responsible enzyme. BK and BK[1-5] N-terminal hydrolysis was optimal at neutral pH, was inhibited by 2-mercaptoethanol, dithiothreitol, o-phenanthroline and EDTA, but was unaffected by the aminopeptidase inhibitors amastatin, puromycin and diprotin A, the endopeptidase-24.11 inhibitors phosphoramidon and ZINCOV, and the ACE and CPN inhibitors captopril and D,L-mercapto-methyl-3-guanidinoethylthiopropanoic acid (MERGETPA), respectively. Although kallidin (Lys-BK) was not metabolized directly by APP, conversion to BK by plasma aminopeptidase M (EC 3.4.11.2) resulted in subsequent degradation by APP. BK analogs containing N-terminal Arg1-Pro2 bonds, including [Tyr8-(OMe)] BK and [Phe8 psi(CH2NH)Arg9]BK (B2 agonists), des-Arg9-BK and [D-Phe8]des-Arg9-BK (B1 agonists), and [Leu8]des-Arg9-BK (B1 antagonist), were degraded by APP with Km and Vmax values comparable to those found for BK (Km = 19.7 +/- 2.6 microM; Vmax = 12.1 +/- 1.2 nmol/min/mL). In contrast, B2 antagonists containing D-Arg0 N-termini, including D-Arg[Hyp3,Thi5.8,D-Phe7]BK and D-Arg[Hyp3,D-Phe7,Phe8 psi(CH2NH)Arg9]BK, were resistant to APP-mediated hydrolysis. These data support a role for plasma aminopeptidase P in the degradation of circulating kinins, and a variety of B2 and B1 kinin agonists and antagonists. However, APP does not participate in the degradation of D-Arg0-containing antagonists.
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PMID:Metabolism of bradykinin agonists and antagonists by plasma aminopeptidase P. 165 Oct 78

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A ('angiotensin-converting enzyme') and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.
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PMID:Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid. 265 79

In this paper we report that while 55% of the total post-proline dipeptidyl-aminopeptidase activity in guinea-pig brain is associated with the soluble fraction of the cells, the remaining activity is widely distributed throughout the particulate fractions. A significant portion of this particulate activity is, however, associated with a synaptosomal membrane fraction. The specific activity of this enzyme rose as the synaptosomal membrane fraction was prepared from a synaptosomal fraction and had previously risen at the synaptosomal fraction was prepared from a postmitochondrial pellet. The synaptosomal membrane post-proline dipeptidyl-aminopeptidase was released from the membrane by treatment with Triton X-100 and partially purified by chromatography on Sephadex G-200. By contrast with the soluble enzyme the partially purified solubilised synaptosomal membrane post-proline dipeptidyl-aminopeptidase was not inhibited by 1.0 mM p-chloromercuribenzoate, 1.0 mM N-ethylmaleimide or 0.5 mM puromycin but was inhibited by 0.5 mM bacitracin. The partially purified solubilised enzyme was capable of releasing His-Pro from His-Pro-Val, His-Pro-Leu, His-Pro-Phe and His-Pro-Tyr and of releasing Gly-Pro from Gly-Pro-Ala but could not release Arg-Pro from Arg-Pro-Pro or from Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (bradykinin). It was also unable to release Pro-Pro from Pro-Pro-Gly or Glp-Pro from Glp-Pro-Ser-Lys-Asp-Ala-Phe-Ile-Gly-Leu-MetNH2 (eledoisin). Using [Pro-3H]thyroliberin we show that the membrane-bound enzyme converts His-ProNH2, produced by the action of the synaptosomal membrane pyroglutamate aminopeptidase, to His-Pro thus competing with the spontaneous cyclisation of His-ProNH2 to His-Pro diketopiperazine. Purified preparations of synaptosomal membrane pyroglutamate aminopeptidase were used to generate His-ProNH2, which could then be converted to His-Pro by the presence of the partially purified synaptosomal membrane post-proline dipeptidyl-aminopeptidase. This preparation was free of contaminating post-proline cleaving endopeptidase, carboxypeptidase P, aminopeptidase P, prolyl carboxypeptidase or proline dipeptidase.
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PMID:Post-proline dipeptidyl-aminopeptidase from synaptosomal membranes of guinea-pig brain. A possible role for this activity in the hydrolysis of His-ProNH2, arising from the action of synaptosomal membrane pyroglutamate aminopeptidase on thyroliberin. 286 1

Proline-containing polypeptides are shown to be sequentially degraded by two aminopeptidases. Clostridial aminopeptidase (EC 3.4.11-) cleaves off any N-terminal amino acid residue including proline from polypeptide chains, but does not cleave the N-terminal secondary peptide bonds involving a prolyl nitrogen. Aminopeptidase P (EC 3.4.11.9) cleaves exclusively such secondary bonds. The two enzymes were immobilized by coupling them covalently to porous amino glass beads. Highly stable preparations were obtained with unchanged pH optimum and thermal stability. The applicability of clostridial aminopeptidase to sequence determination was demonstrated by the time-dependent hydrolysis of enkephalin and Substance P octapeptide. Sequential hydrolysis with the two immobilized enzymes was demonstrated with the proline-containing (Pro-Gly-Pro)10, [Asn1, Val5]angiotensin II, bradykinin, Substance P and tuftsin. Absence of endopeptidase activities was demonstrated by resistance of cytochrome c to hydrolysis and by the ordered release of amino acids during the sequential degradation by immobilized clostridial aminopeptidase and aminopeptidase P.
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PMID:Sequential hydrolysis of proline-containing peptides with immobilized aminopeptidases. 683 Aug 20

Peptidases which are specific for proline residues have been described and include endopeptidases (post-proline cleaving enzyme and proline specific endopeptidase), N-terminal exopeptidases (post-proline dipeptidyl aminopeptidase, proline iminopeptidase, aminopeptidase P), C-terminal exopeptidases (prolylcarboxypeptidase, and carboxypeptidase P) and dipeptidases (prolyl dipeptidase and proline dipeptidase). The properties, distinguishing charcteristics, and possible significance of these proline specific endo- and exopeptidases are discussed. In addition, reference is made to a series of enzymes which can hydrolyze proline containing peptide bonds, but which are not specific for proline.
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PMID:Proline specific endo- and exopeptidases. 699 12

The distribution of brush-border endopeptidase-2, aminopeptidase W, carboxypeptidase P, and aminopeptidase P along the rat and rabbit intestine was examined. In both species, aminopeptidases P and W increased distally and reached the highest in the ileum; their activities in the ileo-caecal junction were the lowest. Endopeptidase-2 had a uniform intestinal distribution in both species with the highest activity in the ileum and little activity in the ileo-caecal junction or caecum. With a distribution similar to that of endopeptidase-2, carboxypeptidase P also had high activity in the ileum in rats and rabbits.
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PMID:Comparison of distribution of brush-border exo- and endopeptidases in rat and rabbit intestine. 789 3

The longitudinal distribution of brush-border endopeptidase-24.11, endopeptidase-2, aminopeptidase W, angiotensin-converting enzyme (ACE), dipeptidyl peptidase IV (DPP IV), carboxypeptidase P, and aminopeptidase P in the rat intestine was determined. The jejunum has the highest activities of endopeptidase-24.11 and ACE while the ileum has the highest activities of aminopeptidase W and carboxypeptidase P, and the jejunoileal junction has the highest activity of aminopeptidase P. The jejunum and ileum have similar activities of DPP IV. The profiles of differential hydrolysis of neurotensin and acetylneurotensin (8-13) along the intestine agree with distribution of endopeptidase-24.11 and ACE, suggesting that amino acid sequences of peptides and the substrate specificity of enzymes will determine site-dependent hydrolysis. There is substantial similarity in the intestinal distribution of peptidases in the human, rat, and rabbit.
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PMID:Distribution of brush-border membrane peptidases along the rat intestine. 793 32

To elucidate the effect of bradykinin (BK) on airway epithelial ion transport function and its modulation by endogenous peptidases, we studied the electrical properties of canine cultured tracheal epithelium under short-circuited conditions in vitro. Addition of BK to the mucosal side of Ussing chamber increased short-circuit current (SCC) in a dose-dependent manner, the maximal rise from the baseline value (delta SCC max) and the concentration required to produce a half-maximal effect being 7.1 +/- 0.7 microA/cm2 (p < 0.001) and 3.9 +/- 1.0 x 10(-7) M, respectively. This effect was greatly attenuated by the B2-receptor antagonist (D-Arg, Hyp3, Thi5,8, d-Phe7)-BK but not by the B1-receptor antagonist (Des-Arg9, Leu8)-BK. Blockade of angiotensin converting enzyme and aminopeptidase P by captopril and mercaptoethanol did not alter the BK-induced increase in SCC. On the other hand, phosphoramidon and MERGAPTA, inhibitors of neutral endopeptidase and carboxypeptidase N, respectively, strengthened the effect of BK. These results suggest that BK stimulates airway epithelial electrical properties through the activation of B2-receptor subtype, and that endogenous peptidases including neutral nedopeptidase and carboxypeptidase N may play a modulatory role in this action of BK.
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PMID:[Effect of bradykinin on airway epithelial ion transport and its modulation by endogenous peptidases]. 833 17


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