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)

The activities of the brain L-asparaginase and angiotensin converting enzyme (ACE), and the plasma cortisol level were found to be decreased in the rats implanted with morphine (M) containing pellets. Even though 10 mg/kg of naloxone (N) itself showed an inhibitory effect on ACE it abolished the inhibitions seen in the M dependent rats five min following subcutaneous injection. The chronic administration of L-aspartic acid (ASP) during the development of physical dependence or just before the N injection prevented the increase of the plasma cortisol caused by N. It is concluded that in addition to the inhibition of the brain L-asparaginase activity which was previously hypothesized to be the main reason of the development of physical dependence on opiates as a result of the related experimental and clinical data, the inhibition by M of the brain ACE activity may take part in the development of physical dependence. With regard to the plasma cortisol level, the concomitant administration of ASP with M blocks, to a great extent, the development of physical dependence on opiate. The single dose of ASP administration before N injection prevents the effect of N, the manifestation of abstinence syndrome.
 ...
PMID:Brain asparaginase, ACE activity and plasma cortisol level in morphine dependent rats: effect of aspartic acid and naloxone. 302 85

The brain and lung angiotensin converting enzyme (ACE) activities of the mice injected with 10 mg/kg morphine and/or naloxone, 200 mg/kg D- and/or L-aspartic acid were spectrophotometrically determined. Morphine, naloxone, D- and L-aspartic acid alone inhibited both brain and lung ACE activities whereas the combinations of morphine with naloxone, D-aspartic acid with L-aspartic acid and morphine with naloxone + L-aspartic acid showed no inhibitory effect on the brain ACE. While naloxone or L-aspartic acid partly antagonized the suppression of morphine on the lung ACE their combination completely prevented morphine from inhibiting the lung ACE. In the in vivo experiments performed on the brain and lung homogenates of the untreated mice the determination of the ACE activity in the incubating media containing 3.10(-3) M morphine or naloxone, 10(-2) M D- or L-aspartic acid showed a significant decrease in the activity. But no in vitro antagonistic effect was found by using the combinations of the drugs used in the study. The antagonism seen in the in vivo experiments was considered as an indirect one. And the relationship between the inhibitory effect of morphine, naloxone and D-aspartic acid, their suppressive effect on drinking and their beneficial effects in various forms of shock was discussed.
 ...
PMID:The effect of morphine, naloxone, D- and L-aspartic acid on the brain and lung ACE in mice. 610 Oct 60

Bovine lung angiotensin I-converting enzyme is rapidly and irreversibly inactivated by p-[N,N-bis(chloroethyl)amino]phenylbutyric acid (chlorambucil) and by the chlorambucil derivative of L-proline (chlorambucyl-proline). Chlorambucil is a nitrogen mustard alkylating agent that is used as an antineoplastic drug. At any one concentration, the inactivation is pseudo-first order with time. Inhibition by both substances is active site directed as suggested by the formation of a reversible enzyme-inhibitor complex prior to the alkylation reaction and by the fact that L-Phe-L-Pro, a reversible inhibitor which is competitive with substrate, is also competitive with both irreversible inhibitors in protecting the enzyme against inactivation. The second order rate constant for inactivation increases in the pH range 5-8 and reaches a value of 3.5 X 10(3) M-1 . min-1 for chlorambucil and 4.8 X 10(2) M-1 . min-1 for chlorambucyl-proline. Chlorambucyl [U-14C]L-proline reacts 1:1 with the converting enzyme and the uptake of radioactivity paralleled the loss of enzyme activity with and without protection by Phe-Pro. Once bound, the radioactive chlorambucyl proline was released (as the dihydroxy derivative) by hydroxide ion with a second order rate constant of 2.2 M-1 . min-1 at 25 degrees C. The radioactive label is also removed by hydroxylamine at pH 10. The lability of the irreversibly bound inhibitor in alkali and in hydroxylamine indicates that an ester bond is formed by the alkylation of an aspartic acid or glutamic acid side chain.
 ...
PMID:Irreversible inhibition of bovine lung angiotensin I-converting enzyme with p-[N,N-bis(chloroethyl)amino]phenylbutyric acid (chlorambucil) and chlorambucyl L-proline and with evidence that an active site carboxyl group is labeled. 627 65

1. A method is described for the measurement of [des-Asp1]-angiotensin I (ANG I 1/2) in blood. 2. Exogenous ANG I 1/2 was rapidly metabolized in conscious sodium replete sheep. 3. Inhibition of angiotensin converting enzyme activity by SQ 14 225 (captopril) abolished the production of angiotensin III (ANG III) and the pressor response to infused ANG I 1/2. 4. The endogenous blood concentration of ANG I 1/2 was very low and not significantly elevated by sodium depletion. 5. Although in vivo pulmonary conversion of ANG I 1/2 to ANG III may occur, this pathway appears to be only of minor importance in sheep. 6. In the presence of converting enzyme inhibition by SQ 14 225, the arteriovenous ratio of ANG I 1/2 was 1.29 (s.e.m. = 0.25). This indicates pulmonary production of ANG I 1/2 and the presence in the lung of a peptidase which hydrolyses aspartic acid from angiotensin I.
 ...
PMID:In vivo conversion of [des-Asp1]-angiotensin I to [des-Asp1]-angiotensin II in conscious sheep. 675 85

The design, synthesis, and biochemical profile of meta-substituted benzofused macrocyclic lactams are described. The meta-substituted benzofused macrocyclic lactams were designed to have a degree of flexibility allowing the amide bond to occupy two completely different conformations while maintaining sufficient rigidity to allow for strong interaction between enzyme and inhibitor. Using TFIT, a novel molecular superimposition program, it was shown that the meta analogs could be readily superimposed onto our ACE inhibitor template whereas no low-energy superimpositions of the ortho-substituted macrocycles could be found. The macrocycles were prepared by tethering aldehyde 1 derived from S-glutamic acid or S-aspartic acid to a meta-substituted phosphonium bromide 2. Homologation to a monocarboxylic acid methyl ester malonate followed by deprotection and cyclization gave the macrocyclic frame. Further manipulation gave the desired compounds. Unlike the ortho-substituted benzofused macrocyclic lactams described in the previous paper which are selective NEP inhibitors, the meta-substituted compounds are dual inhibitors of both NEP and ACE. The most potent member of this new series, compound 16a, inhibited both enzymes with an IC50 = 8 nM in NEP and 4 nM in ACE.
 ...
PMID:Meta-substituted benzofused macrocyclic lactams as zinc metalloprotease inhibitors. 904 41

The physiological functions of angiotensin I-converting enzyme (ACE) are not limited to its cardiovascular role. ACE constantly degrades N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a natural circulating regulator of the hematopoietic stem cell proliferation, and thereby may be involved in hematopoietic stem cell regulation. AcSDKP is hydrolyzed 50-fold faster by the N-domain active site compared to the C-domain active site. The aim of the present study was to investigate which aminoacid residues from AcSDKP are required to ensure N-domain specificity. Several peptides were designed by progressively increasing the length of the peptidic chain from a tripeptide to a pentapeptide. Kinetic studies of the wild-type ACE and of the two ACE mutants containing a single active domain (N- or C-domain) were performed using Bz (benzoyl) Asp-Lys-Pro, benzoyl-glycyl (Bz-Gly)-Asp-Lys-Pro, and Bz-Gly-Ser-Asp-Lys-Pro (with its intermediate product Bz-Gly-Ser-Asp) as substrates. The unexpected importance of an aspartic acid in the P1 position was discovered, as well as the interaction of the P2 and P3 positions in the substrate to increase or decrease N-domain specificity. Substrates longer than five residues may involve interdependence between subsites. Finally, the discovery of highly specific and novel N-domain substrates cannot be predicted from single subsite mapping, but may require other approaches such as combinatorial peptide libraries.
 ...
PMID:N-domain selectivity of angiotensin I-converting enzyme as assessed by structure-function studies of its highly selective substrate, N-acetyl-seryl-aspartyl-lysyl-proline. 1003 45

Two monohydroxamates of l-aspartic acid beta-hydroxamate (AAH) and l-glutamic acid gamma-hydroxamate (GAH) were used for testing antioxidant and angiotensin converting enzyme (ACE) inhibitory activities in comparison with those of asparagine and glutamine, respectively. The half-inhibition concentrations, IC(50), of scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) were 36 and 48 microM and against superoxide radicals were 18.99 and 6.33 mM, respectively, for AAH and GAH. However, no activities of asparagine and glutamine were found. AAH and GAH also exhibited activities against peroxynitrite-mediated dihydrorhodamine 123 oxidations and hydroxyl radical-mediated DNA damage. For ACE inhibitory activities, the IC(50) values were 4.92 and 6.56 mM, respectively, for AAH and GAH. The ACE hydrolyzed products on the TLC chromatogram also confirmed the inhibitory activities of the two amino acid hydroxamates on ACE. When 1.23 mM AAH was added, AAH showed competitive inhibitions against ACE, and the apparent inhibition constant (K(i)) was 2.20 mM.
 ...
PMID:Monohydroxamates of aspartic acid and glutamic acid exhibit antioxidant and angiotensin converting enzyme inhibitory activities. 1508 Jun 51

A rapid capillary electrophoresis method for routine determination of two amino acids, L-ornithine and L-aspartic acid, in human plasma is reported. The method runs automatically, requires a minimum of sample preparation and moreover includes no extensive extraction and no gradient or derivatization procedure. Analyses were performed on an uncoated silica capillary using buffer solution composed with 10 mM sodium tetraborate and 1 M sodium hydroxide (pH=10.0). A capillary electrophoresis P/ACE system equipped with UV detection (200 nm), an automatic injector, a fluid cooled cartridge and System Gold data station was used in this study. The total analysis time under these conditions was 8.0 min. The calibration curve was linear in the range 10-280 microg mL-1 for L-aspartic acid and 20-280 microg mL-1 for L-ornithine (for both amino acids, r=0.999). The method was validated by inaccuracy (bias) and precision (RSD) studies by analysing samples. The method was successfully applied to the quantitative determination of L-ornithine-L-aspartate in human plasma and could be useful for clinical and bioavailability investigations.
 ...
PMID:Validated method for L-ornithine-L-aspartate analysis in human plasma by capillary electrophoresis. 1607 10

It is common for small tandem peptide multimer genes to be indirectly inserted into expression vectors and fused with a protein tag. In this study, a multimer of the tandem angiotensin I-converting enzyme inhibitory peptide (ACE-IP) gene was directly transferred to a commercially available vector and the designed gene was expressed as a repeated peptide in Escherichia coli BL21(DE3)pLysS. The process further developed in our study was the construction of six-repeated ACE-IP synthetic genes and their direct insertion. Protein expression in inclusion bodies was confirmed by SDS-PAGE and Western blot. Acid hydrolysis of inclusion bodies produced single-unit peptides through cleavage of the aspartyl-prolyl bonds. This cleaved recombinant peptide (rACE-IP) was purified using immuno-affinity chromatography followed by reversed phase-HPLC. 105-115 mg of the lyophilized recombinant peptide was obtained from 1 L E. coli culture. In vitro biological activity of rACE-IP was indistinguishable from that of the natural peptide produced by hydrolysis in artificial gastric juice or by acidic hydrolysis. The rACE-IP prepared by recombinant DNA technology and solid-phase synthesis methods showed a similar IC(50). This strategy could be used for the expression of important peptides, which have N-terminal proline (P) and C-terminal aspartic acid residues (D) for commercial applications, e.g. functional foods and drinks.
 ...
PMID:Tandem multimer expression of angiotensin I-converting enzyme inhibitory peptide in Escherichia coli. 1939 4

Leigh syndrome can be caused by defects in both nuclear and mitochondrial genes involved in energy metabolism. Recently, an increasing number of mutations in mitochondrial DNA encoding regions, especially in NADH dehydrogenase (respiratory chain complex I) subunits, have been reported as causative of early onset Leigh syndrome. We describe a patient whose fetal brain ultrasound demonstrated periventricular pseudocyst suggestive of a possible mitochondrial disorder who presented postnatally with Leigh syndrome. A muscle biopsy demonstrated a partial decrease in complex I and pyruvate dehydrogenase (PDH-E1 alpha) activity. Sequencing of the PDH-E1 alpha gene did not reveal any mutation. Sequencing of the mtDNA revealed a novel heteroplasmic G10254A (D66N) mutation in the ND3 gene. This change results in a substitution of aspartic acid to asparagine in a highly conserved domain of the ND3 subunit. The mutation could not be detected in the mother's blood or urine sediment. Blue native gel electrophoresis of muscle mitochondria revealed a normal size, albeit a decreased level of complex I. The G10254A substitution in the mtDNA-ND3 gene is another cause of maternally inherited Leigh syndrome. This case demonstrates that periventricular pseudocysts may be the initial in utero presentation in patients with mitochondrial disorders. We emphasize the importance of screening the mtDNA in pediatric patients as the first step in molecular diagnosis of Leigh syndrome.
 ...
PMID:Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. 2020 74


1 2 Next >>