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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The two isozymes of human angiotensin converting enzyme (ACE; EC 3.4.15.1) have recently been cloned and sequenced. 2. The larger, endothelial isozyme has two highly similar internal domains each bearing a putative catalytic site. In contrast the smaller, testicular isozyme has a single catalytic site corresponding to the C-terminal domain of endothelial ACE and represents the ancestral, non-duplicated form of the gene. 3. Both isozymes are anchored in the plasma membrane by a single hydrophobic transmembrane polypeptide located near the C-terminus, and both are extensively N-glycosylated. 4. The testicular isozyme may also be O-glycosylated. 5. The soluble form of ACE in plasma, seminal fluid and other body fluids appears to be derived from the membrane-bound endothelial isozyme by a post-translational modification. 6. ACE has a complex substrate specificity with peptidyl tripeptidase or endopeptidase action on certain peptides, as well as the classical peptidyl dipeptidase activity. 7. Numerous potent inhibitors of the enzyme have been developed and used successfully in the treatment of hypertension, but some of the observed side effects may be due to inhibition of other zinc metalloenzymes. 8. Both endothelial and testicular ACE are highly conserved between species, indicative of the essential role(s) of the enzyme in blood pressure regulation and other physiological processes.
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PMID:Angiotensin converting enzyme: implications from molecular biology for its physiological functions. 165 Jul 17

We have studied the degradation of bradykinin, lysyl bradykinin and des-Arg9-bradykinin by the angiotensin converting enzyme. Bradykinin was cleaved at two sites to produce the pentapeptide Arg-Pro-Pro-Gly-Phe plus dipeptides Ser-Pro and Phe-Arg. Lysyl bradykinin was cleaved similarly to release the same dipeptides plus the hexapeptide Lys-Arg-Pro-Pro-Gly-Phe. The tripeptidase activity of ACE was observed when des-Arg9-bradykinin was digested. A single cleavage yielded the above pentapeptide plus Ser-Pro-Phe. Although des-Arg9-bradykinin was the most rapidly digested, when mixtures of des-Arg9-bradykinin and bradykinin or lysyl bradykinin were tested, virtually all of the bradykinin and most of the lysyl bradykinin was digested prior to the onset of digestion of des-Arg9-bradykinin. This was shown to be due to inhibition of des-Arg9-bradykinin cleavage by kinins and kinin-degradation products. The order in terms of potency was bradykinin greater than lysyl bradykinin greater than Ser-Pro much greater than Phe-Arg greater than Arg-Pro-Pro-Gly-Phe. The concentration of chloride ion was an important parameter which affected the rate of digestion of each substrate examined. des-Arg9-bradykinin was not digested by ACE in the absence of sodium chloride and the rate of digestion increased as the chloride concentration was increased to 100-150 mM. On the other hand, increasing NaCl concentration was inhibitory for bradykinin digestion. The rate of Lys-bradykinin digestion was increased from 0 to 1 mM NaCl and decreased thereafter up to physiologic concentration. A half-maximal rate was seen at 100-150 mM NaCl compared to no salt. Of the divalent cations examined, cupric ion inhibited further digestion of des-Arg9-bradykinin at physiologic concentrations. Our data indicate that the rate of degradation of kinins and the nature of the stable final cleavage products in plasma or serum (studied in vitro) are dependent upon the effects of chloride ion, metal ions, and the kinetic effects of multiple metabolites produced by at least two kininases.
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PMID:Studies of the digestion of bradykinin, Lys-bradykinin, and des-Arg9-bradykinin by angiotensin converting enzyme. 301 4

Previous studies have shown that the metabolism of delta sleep-inducing peptide (DSIP) in the blood-brain barrier (BBB) is catalyzed by amino-peptidases. In this study, we have shown that peptidyl dipeptidase A in cultured bovine brain microvessel endothelial cells (BBMEC), a model of the BBB, and a purified form of this enzyme can also metabolize DSIP by sequential hydrolyses of dipeptides or tripeptides from the carboxyl terminus of this nonapeptide. Both the dipeptidase and tripeptidase activity associated with peptidyl dipeptidase A can be inhibited by captopril. Total stabilization of DSIP to metabolism in BBMEC could be achieved by inclusion of an inhibitor of peptidyl dipeptidase A (e.g., captopril) and an inhibitor of aminopeptidases (e.g., bestatin).
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PMID:Peptidyl dipeptidase A-catalyzed metabolism of delta sleep-inducing peptide in bovine brain microvessel endothelial cells: a cell culture model of the blood brain barrier. 776 73

A soluble 67 kDa angiotensin-converting enzyme (ACE) has been purified by lisinopril-Sepharose affinity column chromatography from adult houseflies, Musca domestica. The dipeptidyl carboxypeptidase activity towards benzoyl-Gly-His-Leu was inhibited by captopril (IC50 50 nM) and fosinoprilat (IC50 251 nM), two inhibitors of mammalian ACE, and was activated by Cl- (optimal Cl- concentration 600 mM). Musca ACE removed C-terminal dipeptides from angiotensin I, bradykinin [Leu5]enkephalin and [Met5]enkephalin and also functioned as an endopeptidase by hydrolysing dipeptideamides from [Leu5]enkephalinamide and [Met5]enkephalinamide, and a dipeptideamide and a tripeptideamide from substance P. Musca ACE was also able to cleave a tripeptide from both the N-terminus and C-terminus of luteinizing hormone-releasing hormone, with C-terminal hydrolysis predominating. Maximal N-terminal tripeptidase activity occurred at 150 mM NaCl, whereas the C-terminal tripeptidase activity continued to rise with increasing concentration of Cl- (0-0.5 M). Musca ACE displays properties of both the N- and C-domains of human ACE, indicating a high degree of conservation during evolution of the substrate specificity of ACE and its response to Cl-.
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PMID:The endopeptidase activity and the activation by Cl- of angiotensin-converting enzyme is evolutionarily conserved: purification and properties of an an angiotensin-converting enzyme from the housefly, Musca domestica. 867 80