Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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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)

To develop means of measuring angiotensin converting enzyme of endothelial cells in culture, we have synthesized benzoyl-Phe-Ala-Pro-OH (I), benzoyl-Pro-Phe-Arg-OH (II) and benzoyl-Gly-His-Leu-OH (III), each bearing a 3H-atom on the para-position of its benzoyl moiety. All three of the acylated tripeptides are substrates for the enzyme. Substrate I exhibits the lowest Km (12.5 micrometer) and yields the most sensitive assay: the enzyme of 10(6) cells can be measured in a 30 min incubation at 37 degrees C. Radiolabelled reaction product is separated from substrate by extraction of acidified reaction mixture with an organic solvent, and the rate of formation of product can be quantified by liquid scintillation counting of the organic phase. Substrate III can also be used to measure angiotensin converting enzyme of cells but requires longer incubations (180--240 min) and high salt concentrations (0.75 M Na2SO4). Substrate II is not specific: it is hydrolyzed by more than one enzyme of endothelial cells.
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PMID:New substrates for the radioassay of angiotensin converting enzyme of endothelial cells in culture. 3 10

Based on fluorometric determination of a dipeptide histidil-leucine, which is splitted off from a synthetic substrate (Cbz-Phe-His-Leu) by carboxycathepsin (carboxydipeptidyl peptide hydrolase), a method was developed for estimation of the enzymatic activity in human blood serum. The method is characterized by simplicity and high sensitivity; Use of small amount of blood serum (about 0.03 ml) was possible. In normal human blood serum the carboxycathepsin activity varied from 7.5 to 18 nmoles of the dipeptide, liberated per mg of protein per hr.
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PMID:[Determination of carboxycathepsin (peptidyl dipeptidase) activity in human blood serum]. 16 83

A fluorimetric assay of dipeptidyl carboxypeptidase is described. It involves incubation at 37 degrees C with the substrate, Z-Phe-His-Leu, and reaction of the dipeptide His-Leu which is released upon enzymatic hydrolysis, with o-phthalaldehyde to yield a fluorescent compound. The method is simple, precise and sensitive. The assay in serum is conveniently performed on 20 mul samples. Normal values in human serum range from 0.04 to 0.22 U/l.
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PMID:Fluorimetric determination of dipeptidyl carboxypeptidase. (angiotensin-I-converting enzyme). 16 29

Some analogues of bradykinin, especially with replacements by other amino acids of phenylalanine in position 8, have been investigated for enzymatic stability against kininase II from rat duodenum microsomes and rat uterus plasma membranes, respectively. As compared with bradykinin, two of the analogues, [8-erythro-beta-phenylserine]- and [8-erythro-alpha-Amino-beta-phenylbutyric acid]-Bradykinin were stable to enzymatic degradation. Therefore, the latter may be used for studies in hormone-receptor interaction.
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PMID:[Stability of some bradykinin analogues against kininase II (author's transl)]. 17 30

The N-acyltripeptide 2-aminobenzoylglycyl-p-nitrophenylalanylproline was synthesized and applied as a substrate in the assay of angiotensin-I-converting enzyme from calf lung and human serum, and of the bacterial dipeptidyl carboxypeptidase from Escherichia coli. This compound belongs to a new class of substrates for proteolytic enzymes, having the general structure F--X--Q in which fluorescence of group F is quenched by intramolecular interaction with the group Q. Enzymatic cleavage of the peptide chain (X stands for one or more amino acid residues) generates the unquenched F-containing derivative and the resulting fluorescence is used for quantitative measurement of the hydrolysis rate. Cleavage of the Gly-Phe(NO2) peptide bond in the weakly fluorescent 2-amino-benzoylglycyl-p-nitrophenylalanylproline molecule results in appearance of the 71 times higher fluorescence (lambdamax = 415 nm) of 2-aminobenzoylglycine. Continuous recording of the rising fluorescence allows convenient, sensitive and specific determination of the enzymatic activity, applicable to crude enzyme preparations and human serum. The activity of the mammalian enzyme, measured by this method, is enhanced by Cl- ions and inhibited by low concentrations of EDTA and [Asn1, Val5]angiotensin II. Kinetic measurements showed Michaelis-Menten behavior, Km = 0.21 +/- 0.1 mM and 0.16 +/- 0.1 mM for the calf lung and the bacterial enzyme respectively.
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PMID:An intramolecularly quenched fluorescent tripeptide as a fluorogenic substrate of angiotensin-I-converting enzyme and of bacterial dipeptidyl carboxypeptidase. 20 42

Endothelial cells are a major source of kininase enzymes including kininase II. Kininase II is situated along the plasma membrane, not as an ecto-enzyme but as an enzyme synthesized by the endothelial cells themselves. However, it is likely that endothelial cells do more than degrade kinins. These cells are contractile and may possess kinin receptors; a possibility supported by the fact that kinins stimulate endothelial cells to form and release prostaglandin-related substances. In addition, we have found that endothelial cells in culture are reactive with antibodies to alpha 2-macroglobulin. Endothelial cells can hydrolyze [3H]Pro-Phe-Arg-anilide, a kallikrein substrate, but the reaction is not inhibited by soya bean trypsin inhibitor (SBTI) or Trasylol. Possibly kallikrein or a related trypsin-like enzyme is bound to alpha 2-macroglobulin and is not free to react with the inhibitors. Thus, endothelial cells can bind and inhibit kallikrein-like enzymes, degrade kinins and respond to kinin stimulation.
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PMID:Endothelial cells and components of the kallikrein-kinin system. 22 4

Several peptides were investigated for their inhibitory capacity against dipeptidyl carboxypeptidase (angiotensin-converting enzyme) from human seminal fluid. The strongest inhibitor was the nonapeptide SQ 20881. A marked inhibition was also shown by the compounds Phe-Ala-Pro and Boc-Phe-Ala-Pro, which behaved as competitive inhibitors. Among the peptides related to angiotensin, angiotensin III was the strongest inhibitor, followed by angiotensin II and the C-terminal hexapeptide of angiotensin II. The results indicate the dipeptidyl carboxypeptidase of human semen is very similar to pulmonary dipeptidyl carboxypeptidase in its susceptibility to peptide inhibitors. In view of these and other previously reported similarities, it is possible that both enzymes are identical.
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PMID:Study of peptides inhibiting the angiotensin-converting enzyme of human seminal plasma. 23 29

At extremely low concentrations, in the picomole and the nanomole range, bradykinin produces contraction and relaxation of smooth muscle in the gastrointestinal and the urogenital tract. At the target organ, bradykinin interacts with discriminator proteins of the plasma membranes and triggers, via changes in certain membrane functions, its biological response:--The binding to the discriminator makes specific conformative and constitutional demands on the nonapeptide. The binding results from an angular conformation which exists in the solution. The complete sequence is responsible for this specific conformation. Consequently, the biological activity of partial sequences is low. The conformational analysis of analogues used in studies on the mechanism of action showed but slight differences from bradykinin. The interaction of these analogues with the discriminator protein is disturbed to a varying extent by modifications at positions 1, 5, 8 and 9 in the side chains. The affinity for the discriminator is affected, dependently on the respective configuration, by substitution on the beta-C atom in the two phenylalanine residues.--Bradykinin is not only bound to, but also degraded at, the plasma membranes of the rat uterus and duodenum. The bradykinin-degrading enzyme has been characterized as a kininase II with the aid of various inhibitors. The conformative and configurative prerequisites decisive for enzymatic degradation are others than those decisive for binding to the discriminator.--The changes in the activities of the membrane-bound adenylate and guanylate cyclases (produced by the bradykinin-discriminator complex) that take place at the rat duodenum and uterus in the presence of extracellular calcium ions contrast with each other: At the duodenum, the ratio between these two cyclic nucleotides is changed in favour of adenylate cyclase; and at the uterus, in favour of guanylate cyclase; Substances which increase or decrease the cAMP level may also potentiate or inhibit the relaxation of the duodenum. These bradykinin-induced changes in enzyme activity must be considered in connection with other effectors, e.g. prostaglandins and calcium ions.--The calcium-ion-dependence of the effect of bradykinin on the guinea-pig ileum and the rat uterus indicates the importance of these ions as additional second messengers. Bradykinin stimulates the influx of calcium ions into the ileum; it is ineffective if no extracellular calcium ions into the ileum; it is ineffective if no extracellular calcium ions are available. It seems that intracellular and membranal calcium is mobilized in the uterus, which is evidenced by results from experiments with EGTA on the isolated organ and by the release of calcium from plasma membranes after application of bradykinin. It is assumed that the observed changes in membrane functions are induced by the peptide-discriminator complex simultaneously and not in the form of a causal chain.
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PMID:[On the mode of action of bradykinin on smooth muscle (author's transl)]. 39 90

Converting enzyme activity was studied in endothelial cells, isolated from pig pulmonary arteries and aorta by exposure to collagenase. The measure was based on the release of His-Leu from Z-Phe-His-Leu was related to the DNA content of the cellular suspension. The same activity was found in the two types of endothelium: 1 nmol His-Leu/mug DNA per 30 min. Subendothelial cells showed a very low activity, amounting to 10% of the value found for the endothelium. The enzyme activity was 2inhibited by the nonapeptide SQ 20881, EDTA, and the lack of Cl- in the same fashion for the two types of endothelium. The presence of another enzyme hydrolyzing His-Leu was detected in both endothelial populations. Isolated fragments of plasma membrane, however, exhibited only converting enzyme activity. It can be concluded that endothelial cells isolated from large vessels of the pulmonary and the systemic circulations have similar properties when dipeptidyl carboxypeptidase activity is measured.
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PMID:Converting enzyme activity in endothelial cells isolated from pig pulmonary artery and aorta. 40 22

Exsanguinated rat liver preparations perfused in situ with oxygenated saline solutions inactivated recirculating bradykinin (BK) at rates of 2.3 to 9.1 and isoleucyl5 angiotensin II (AII) at rates of 2.8 to 15.0 nmoles X min-1 X g-1 of liver, depending on the initial concentration of the peptides in the perfusion fluid (3.1 to 18.9 X 10(-6) M for BK and 8.5 to 17.0 X 10(-6) M for AII). On the other hand, at similar concentrations, recirculation of isoleucyl5 Angiotensin I (AI) for 8 min did not lead to decrease of its biological activity when assayed on the isolated rat uterus. Following a single passage through liver, picomole amounts of both BK and AII were inactivated by about 90% as revealed by assays on a superfused rat uterus. The potency ratio AI:AII, assayed on a superfused rat uterus was 1:22 and changed to 1:5 following a single passage of both peptides through liver. This finding and the separation of 4.9% of AII on carboxymethylcellulose columns following recirculation of AI through rat liver indicate a conversion of AI into AII. The dipeptides Phe-Arg, Ser-Pro and Gly-Phe were identified among the hydrolysis products of perfused BK. A peptidyldipeptide hydrolase (EC 3.4.15) may be responsible for both the BK inactivation and AI conversion. The inactivation of AII cannot be attributed to the same enzyme.
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PMID:Catabolism of vasoactive polypeptides by perfused rat liver. 100 40


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