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)

A dipeptidyl carboxypeptidase, which cleaved the Gly3-Phe4 bond of enkephalins, was purified from guinea pig serum 420-fold. The optimum pH of the enzyme was in the neutral range (pH 7.25), and the molecular weight was estimated to be approx. 280,000. The enzyme hydrolyzed Met- and Leu-enkephalin with Km values of 0.30 and 0.50 mM, respectively. The enzyme was inhibited by metal chelators and p-chloro-mercuribenzoate. Captopril showed high inhibitory potency, while phosphoramidon and Phe-Ala showed no effect on the enzyme activity. Therefore, the obtained enzyme can be classified as an angiotensin-converting enzyme (EC 3.4.15.1). Among the bioactive peptides examined, bradykinin and angiotensin I were hydrolyzed by the enzyme. Angiotensin III showed a stronger inhibitory effect than that of angiotensin II. Substance P, gastrin I, and secretin were also inhibitory toward the enzyme activity. On high-performance liquid chromatography analysis, Met-enkephalin-Arg6-Phe7 and Leu-enkephalin-Arg6 were cleaved sequentially at the second peptide bond of the C terminus. Thus, the dipeptidyl carboxypeptidase in guinea pig serum may play a role not only in the angiotensin-bradykinin system but also in the metabolism of circulating enkephalins and other bioactive peptides.
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PMID:Enkephalin-degrading dipeptidyl carboxypeptidase in guinea pig serum: its properties and action on bioactive peptides. 299 Mar 46

Like angiotensin II (AII) itself, [SAR1] AII induced a biphasic blood pressure response in the conscious chicken--an initial depressor response followed by a pressor response. Angiotensin III, however, induced only a depressor response in the dose range tested. The response to angiotensin I was similar to that to AII, and appeared to be due to its conversion to AII as it was inhibited by prior infusion of the angiotensin converting enzyme inhibitor SQ 20,881. Two angiotensin analog antagonists [SAR1ALA8] AII and [SAR1ILE8] AII inhibited both components of the response to AII, but the pressor response was inhibited at lower concentrations of antagonist than was the depressor response. These findings give further support to the suggestion that the pressor and depressor component of the response to AII in the conscious chicken are mediated via different AII receptors, and indicate the possibility of selective blockade of these two components.
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PMID:Cardiovascular actions of angiotensin in the fowl (Gallus domesticus). II. Angiotensin analog agonists and antagonists. 626 70

When angiotensin fragments, Val-Tyr and Angiotensin III (ANG III), with potent ACE inhibitory activity were intravenously administered to spontaneously hypertensive rat (SHR), a significant reduction of diastolic blood pressure was observed. After incubation of ANG III with SHR plasma, four fragments with ACE inhibitory activity, Val-Tyr (ANG (3-4)) (IC50 = 26.0 microM), Ile-His-Pro-Phe (ANG (5-8)) (11.6 microM), Tyr-Ile-His-Pro-Phe (ANG (4-8)) (457.5 microM), and Val-Tyr-Ile-His-Pro-Phe (ANG (3-8)) (6.55 microM), were confirmed to generate in SHR plasma. Compared the metabolic behavior of ANG II in SHR plasma with that in normotensive Wistar plasma, the initial degradation rate (3.07 nmol/ml/min) in Wistar plasma was about 2-fold higher than that in the SHR one (1.75 nmol/ml/min).
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PMID:Antihypertensive effects of angiotensin fragments in SHR. 754 89