SEARCH · PubMed Health

Results for “LEUCINE AMINOPEPTIDASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources

PubMed1982

Characterization of two uterine proteases and their actions on the estrogen receptor.

We have characterized two previously undetected proteases from the calf uterine cytosol and measured their actions on the estrogen receptor. One is an exopeptidase, purified 60-fold, that hydrolyzed amino acid (lysine-, and alanine-, or leucine-) p-nitroanilide substrates and leucylglycylglycine, did not hydrolyze [14C]methemoglobin, was completely inhibited by 1 mM bestatin or puromycin (specific inhibitors of leucine aminopeptidase like enzymes), and was unable to influence the sedimentation of the 8S form of the estrogen receptor in sucrose gradients containing dilute Tris buffer. A commercial porcine leucine aminopeptidase, like the calf uterine aminopeptidase, did not convert the 8S estrogen receptor to a 4S form. Evidently, removal of the N-terminal amino acid(s) from the estrogen receptor by exopeptidase action cannot alter the sedimentation of the 8S form of the receptor, or the N-terminal amino acid(s) of the receptor is (are) unaccessible or resistant to exopeptidase activity. The second, a receptor-active protease, is an endopeptidase that did not hydrolyze any of the synthetic amide or peptide substrates tested but did possess [14C]methemoglobin-degrading activity and the ability to convert the 8S estrogen receptor to a modified 4S form in sucrose gradients containing dilute Tris buffer. The modified 4S receptor was separable from the native receptor by DEAE-cellulose chromatography. The endopeptidase did not require Ca2+ for activity, and its chromatographic properties were distinctly different from a previously isolated Ca2+-activated protease. It was inhibited by leupeptin or dipyridyl disulfide, suggesting the presence of a thiol group that is essential for its activity. These data indicate that a decrease in the sedimentation rate of the estrogen receptor in sucrose gradients with low salt or a change in the receptor's elution on DEAE-cellulose chromatography is not related to receptor activation but is produced by the receptor-active protease or other proteases.

Animals↗

PubMed1976

Separation of rat muscle aminopeptidases.

By means of chromatography on DEAE-Sephadex, two arylamidases (hydrolysing L-arginine 2-naphthylamide) and three dipeptidyl peptidases (hydrolysing dipeptide 2-naphthylamides) were distinguished in extracts of rat muscle. However, the arylamidase from the larger peak also hydrolysed the dipeptide 2-naphthylamides. Glycyl-L-arginine amide, an alternative substrate for dipeptidyl peptidase I, was not hydrolysed by arylamidase. L-Leucine amide was hydrolysed by an enzyme, presumed to be leucine aminopeptidase, from a separate peak, but was also hydrolysed by arylamidase. Arylamidase, dipeptidyl peptidase III and most of the leucine aminopeptidase could be extracted from the muscle with a neutral salt solution, but dipeptidyl peptidase I was extracted only in the presence of Triton X-100; dipeptidyl peptidase II showed an intermediate extraction behaviour.

Aminopeptidases↗

PubMed1988

Correlation of histoenzymological studies with the response to chemotherapy and survival in breast cancer patients.

The enzyme activity of cancerous tissue and the adjacent normal epithelium of 40 patients with breast cancer was determined. This enzymatic activity was correlated with the responsiveness of those tumors to the chemotherapy. It was found that the presence of cytochrome oxidase and alkaline phosphatase and the absence of leucine aminopeptidase, beta-glucuronidase and dehydrogenases in cancerous tissues was related to good response. On the contrary, the absence of alkaline phosphatase and cytochrome oxidase and the presence of leucine aminopeptidase, beta-glucuronidase and dehydrogenases in the cancerous tissues was related to poor response and therefore to poor survival.

Alkaline Phosphatase↗

PubMed2003

Aerobic biological treatment of synthetic municipal wastewater in membrane-coupled bioreactors.

Membrane-coupled bioreactors (MBRs) offer many benefits compared to conventional biological wastewater treatment systems; however, their performance characteristics are poorly understood. Laboratory-scale MBRs were used to study bacterial adaptations in physiology and community structure. MBRs were fed a mixture of starch, gelatin, and polyoxyethylene-sorbitan monooleate to simulate the polysaccharide, protein, and lipid components of municipal wastewater. Physiological adaptations were detected by measuring ectoenzyme activity while structural dynamics were studied by denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene fragments. As cell biomass accumulated in the MBRs, pollutant removal efficiency initially improved and then stabilized with respect to effluent concentrations of chemical oxygen demand, protein, and carbohydrate. Comparison of the MBR effluent to filtered reactor fluid indicated that a portion of the observed pollutant removal was due to filtration by the membrane rather than microbial activity. The rates of ectoenzyme-mediated polysaccharide (alpha-glucosidase) and protein (leucine aminopeptidase) hydrolysis became relatively constant once pollutant removal efficiency stabilized. However, the maximum rate of lipid hydrolysis (heptanoate esterase) concomitantly increased more than 10-fold. Similarly, alpha-glucosidase and leucine aminopeptidase ectoenzyme affinities were relatively constant, while the heptanoate esterase affinity increased more than 30-fold. Community analysis revealed that a substantial community shift occurred within the first 7 days of operation. A Flavobacterium-like bacterial population dominated the community (>50% of total band intensity) and continued to do so for the remainder of the experiment.

Adaptation, Physiological↗

PubMed2003

Effects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chinese-herb nephropathy.

Chinese-herb nephropathy (CHN) is a progressive renal interstitial fibrosis initially reported after concomitant intake of an anorexigen, (dex)fenfluramine, and a Chinese herb ( Aristolochia fangchi) containing nephrotoxic and carcinogenic aristolochic acid (AA). We thus tested the possible enhancing effect of the active enantiomer dexfenfluramine (DXF) on AA nephrotoxicity in a rat model for CHN. Groups of 12 salt-depleted male Wistar rats received daily subcutaneous injections of 7 mg/kg body weight DXF (DXF group), 7 mg/kg body weight AA (AA group), a combination of the same doses of AA and DXF (AA+DXF group), or vehicle (control group) for up to 35 days. Six animals per group were killed on day 10 and the remaining six on day 35. Renal function was evaluated by determining serum creatinine and urinary leucine aminopeptidase activity. Histological evaluation of kidney samples was performed and tubulointerstitial injuries were semiquantified. The DXF group did not differ from controls for any parameter. Similarly elevated serum creatinine levels, decreased leucine aminopeptidase enzymuria, and renal lesions were observed in the AA and the AA+DXF groups after both 10 and 35 days. The formation of specific AA-DNA adducts in liver and renal tissue samples was assessed by the (32)P-postlabelling method. Specific AA-DNA adduct levels were significantly increased in kidney tissues from AA+DXF rats compared with AA rats. These functional and histological data suggest that DXF does not enhance AA nephrotoxicity in a rat model for CHN. Further investigations are needed to clarify the mechanism by which DXF may enhance AA-DNA adduct formation.

Animals↗

PubMed2005

Regulation and seasonal dynamics of extracellular enzyme activities in the sediments of a large lowland river.

We tested whether seasonal changes in the sources of organic substances for microbial metabolism were reflected changes in the activities of five extracellular enzymes in the eighth order lowland River Elbe, Germany. Leucine aminopeptidase showed the highest activities in the water column and the sediments, followed by phosphatase > beta-glucosidase > alpha-glucosidase > exo-1,4-beta-glucanase. Individual enzymes exhibited characteristic seasonal dynamics, as indicated by their relative contribution to cumulative enzyme activity. Leucine aminopeptidase was significantly more active in spring and summer. In contrast, the carbohydrate-degrading enzymes peaked in autumn, and beta-glucosidase activity peaked once again in winter. Thus, in sediments, the ratio of leucine aminopeptidase/beta-glucosidase reached significant higher medians in spring and summer (5-cm depth: ratio 7.7; 20-cm depth: ratio 10.1) than in autumn and winter (5-cm depth: ratio 3.7, 20-cm depth: ratio 6.3). The relative activity of phosphatase in the sediments was seasonally related to both the biomass of planktonic algae as well as to the high content of total particulate phosphorus in autumn and winter. Due to temporal shifts in organic matter supply and changes in the storage capacity of sediments, the seasonal peaks of enzyme activities in sediments exhibited a time lag of 2-3 months compared to that in the water column, along with a significant extension of peak width. Hence, our data show that the seasonal pattern of extracellular enzyme activities provides a sensitive approach to infer seasonal or temporary availability of organic matter in rivers from autochthonous and allochthonous sources. From the dynamics of individual enzyme activities, a consistent synoptic pattern of heterotrophic functioning in the studied river ecosystem could be derived. Our data support the revised riverine productivity model predicting that the metabolism of organic matter in high-order rivers is mainly fuelled by autochthonous production occurring in these reaches and riparian inputs.

Enzymes↗

PubMed1994

Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical member of the co-catalytic zinc enzyme family.

BACKGROUND: Aminopeptidases specifically cleave the amino-terminal residue from polypeptide chains and are involved in the metabolism of biologically active peptides. The family includes zinc-dependent enzymes possessing either one or two zinc ions per active site. Structural studies providing a detailed view of the metal environment may reveal whether the one-zinc and two-zinc enzymes constitute structurally and mechanistically distinct subclasses, and what role the metal ions play in the catalytic process. RESULTS: We have solved the crystal structure of the monomeric aminopeptidase from Aeromonas proteolytica at 1.8 A resolution. The protein is folded into a single alpha/beta globular domain. The active site contains two zinc ions (3.5 A apart) with shared ligands and symmetrical coordination spheres. We have compared it with the related bovine lens leucine aminopeptidase and the cobalt-containing Escherichia coli methionine aminopeptidase. CONCLUSIONS: The environment and coordination of the two zinc ions in A. proteolytica aminopeptidase strongly support the view that the two metal ions constitute a co-catalytic unit and play equivalent roles during catalysis. This conflicts with the conclusions drawn from the related bovine leucine aminopeptidase and early biochemical studies. In addition, the known specificity of the aminopeptidase for hydrophobic amino-terminal residues is reflected in the hydrophobicity of the active site cleft.

Aeromonas↗

PubMed2004

Effects of rearing density on larval growth and activity of digestive enzymes in Lymantria dispar L. (Lepidoptera: Lymantriidae).

Density dependent responses of 4th, 5th and 6th instar gypsy moth larvae were studied at the level of larval mass, midgut loading and activities of three digestive enzymes (alpha-amylase, trypsin and leucine aminopeptidase). High density significantly reduced larval mass while midgut loading (expressed as relative midgut mass) did not change except in the 5th instar where it was increased at high density. Specific amylase and leucine aminopeptidase activities were not affected by crowding. Specific trypsin activity was on average higher in crowded than in isolated larvae. High density also affected the correlations between midgut protein content and activities of two proteolytic enzymes suggesting differences in regulatory mechanisms of insect digestion. The importance of these changes for survival under stressful conditions is discussed.

Analysis of Variance↗

PubMed1992

In vivo effects of indomethacin on the activity of metal-containing enzymes.

1. Indomethacin injected subcutaneously at a single "ulcerogenic" dose decreased aminooxidase and leucine aminopeptidase activity and did not change alcohol dehydrogenase and ceruloplasmin activity. 2. Indomethacin administered at an oral "therapeutic" dose inhibited aminooxidase activity in small intestinal mucosa but not in liver and did not change leucine aminopeptidase activity in blood, liver and intestinal mucosa; it, however, increased alcohol dehydrogenase and ceruloplasmin activity. 3. The decreased activity of ceruloplasmin and alcohol dehydrogenase by metal deficiency increased after oral indomethacin treatment, reaching the control values when indomethacin was chelated with copper. 4. The results suggest the participation of endogenous metals in the indomethacin effect.

Administration, Oral↗

PubMedDate not supplied

[Activity of several erythrocyte enzymes in chick embryos and chicks after gamma-irradiation].

After irradiation of chick embryos and chicks (1,000 rad), the activity of some erythrocyte enzymes undergoes significant changes. During the 1st day after irradiation of chick embryos, the activity of lactate dehydrogenase leucine aminopeptidase and glutamate pyruvate transaminase decreases. At the 3rd day, the decrease in the activity of glucose-6-phosphate dehydrogenase and acid phosphatase is also observed. In irradiated chicks, the activity of lactate dehydrogenase, leucine aminopeptidase and aldolase decreases within the 1st and the 3rd days, the decrease being most significant for the former two enzymes. At later period (10 and 15 days after irradiation), most significant decrease was found in the activity of glucose-6-phosphate dehydrogenase. The activity of the same enzymes in the blood plasma of irradiated embryos and chicks increases, the increase being most evident for glucose-6-phosphate dehydrogenase.

Acid Phosphatase↗

PubMed1982

Properties and specificity of binding sites for the immunomodulator bestatin on the surface of mammalian cells.

The binding of the immunomodulator bestatin, an inhibitor of cell surface bound leucine aminopeptidase and aminopeptidase B, to mammalian cells of varying origin has been studied. The specific binding of [3H] bestatin was a rapid and saturable process exhibiting one affinity, characterized by an association constant of 0.8 x 10(5) M-1, as determined in the L5178y mouse lymphoma system. Optimal binding was observed at 37 degrees C. L-leucine and L-leucine-beta-naphthylamide prevented the binding, suggesting that the complex was formed between leucine aminopeptidase and bestatin. The protein nature of the bestatin-"receptor" was suggested by its susceptibility to trypsin. Under the conditions used here intracellular translocation of bestatin appeared to be negligible. A maximum of about 2.2 x 10(6) bestatin molecules could bind to L5178y mouse lymphoma cells. Under identical conditions by far the highest amount of bestatin was bound to macrophages from mice. Lower levels were measured with T-lymphocytes; very low binding capacity was observed with B-lymphocytes. Experiments with synchronized L5178y cells revealed a cell cycle dependent change of binding capacity for bestatin; the highest level was observed during the transition from S-to G2 phase and the lowest during G1- and early S phase. These data lend further support to the assumption that the immuno-potentiating activity of bestatin is due to a stimulation of T-lymphocyte proliferation probably mediated through the activation of macrophages.

Adjuvants, Immunologic↗

PubMed1991

Effect of plasma glow, glutaraldehyde and carbodiimide treatments on the enzymic degradation of poly (L-lactic acid) and poly (gamma-benzyl-L-glutamate) films.

The hydrolytic and enzymic degradation of poly(L-lactic acid) (PLA) and poly(gamma-benzyl L-glutamate) (PBGA) films, together with a series of surface treatments, were studied, as a function of exposure time. The degradation of these polymers was monitored by weight loss, contact angle, pH changes and tensile strength studies. Glutaraldehyde treatment retained the maximum strength of PLA in buffer, followed by carbodiimide, compared with control films. On the other hand, plasma glow reversed the effect. The ability of alpha-chymotrypsin, carboxypeptidase, ficin, esterase, bromelain and leucine aminopeptidase to modulate the degradation of PLA and PBGA was also investigated. Addition of these enzymes to the polymer-buffer system reduced the tensile strength of these polymers variably. Among the six enzymes studied, leucine aminopeptidase showed the highest enzymic effect on the degradation of the glutaraldehyde-treated and bare PLA or bare PBGA films. However, glutaraldehyde-cross-linked PLA demonstrated maximum stability in buffers or in all other enzyme systems studied compared with bare PLA. It is conceivable that surface treatments on these polymers might have altered their physical and chemical configuration and the subsequent degradation properties. Surface modifications may provide new ways of controlling the biodegradation of polymers for a variety of biomedical applications.

Biocompatible Materials↗

PubMedDate not supplied

[Blood insulin and characteristics of nitrogen metabolism in organs during myocardial necrosis developing after emotional stress].

Simulation of myocardium necrosis developed after emotional stress led to hyperinsulinemia and hyperglycemia simultaneously with a decrease in arterial-venous difference of oxygen. In control, stress-treated animals, hypoinsulinemia and hyperglycemia were detected. Dissimilar alterations in nitrogen metabolism were observed in heart and brain tissues of the animals with myocardium necrosis under conditions of anomalous insulin secretion and glucose consumption. During the first steps of myocardium necrosis after emotional stress increase in content of nucleic acids, ammonium, urea as well as activation of leucine aminopeptidase were found in heart of the animals. At the same time, a number of compensatory reactions, involved in nitrogen metabolism, were not found in brain of the animals with myocardium necrosis; distinct activation of leucine aminopeptidase was detected in the tissue.

Animals↗

PubMed1981

Evolutionary genetics of Metridium senile. II. Geographic patterns of allozyme variation.

Electrophoretic surveys have demonstrated that populations of the sea anemone Metridium senile along the northeast coast of the United States are polymorphic at four enzyme loci. Phosphoglucose isomerase (PGI) has two alleles in most populations, phosphoglucomutase (PGM) has three alleles, and two leucine aminopeptidase loci have two common alleles each. Phosphoglucose isomerase displays clinial variation and an apparent association with environmental temperature. Phosphoglucomutase shows clinial variation north of Cape Cod for two of the three alleles, while the two leucine aminopeptidase loci are not clinial. All loci show a great deal of variation in populations on Cape Cod, but there is no apparent systematic pattern of this variation. Temperature may be a selective agent in the maintenance of the PGI and PGM clines, although other possibilities cannot presently be completely excluded.

Alleles↗

PubMed1956

Quantitative estimation of lyo- and desmoenzymes in tissue sections with and without fixation.

1. Tissue sections eight microns thick were exposed to various experimental conditions used in histochemistry, and the effect upon the activities of esterase, the phosphatases, leucine aminopeptidase, beta-glucuronidase, and arylsulfatase was determined colorimetrically. 2. Significant differences were found in the amounts of the lyo and desmo fractions of these enzymes. The desmo components were found to be for esterase, alkaline phosphatase, leucine aminopeptidase, acid phosphatase, beta-glucuronidase, and arylsulfatase, (1/3), 2/3, 2/3, (1/2), (1/8), and (1/8) of the total enzymatic activity respectively. 3. Variations in the time and in the temperature at which diffusion was studied and of the pH and salt concentration of the solution into which the sections were placed, resulted in differences in the amount of enzymatic activity which remained in the tissue section. Some enzyme loss by diffusion was noted even after fixation of the tissue section. 4. The significance of the findings with respect to some of the concepts of localization of enzymes in tissue sections was discussed.

Acid Phosphatase↗

PubMedDate not supplied

Lapstatin, a new aminopeptidase inhibitor produced by Streptomyces rimosus, inhibits autogenous aminopeptidases.

Lapstatin, a low-molecular-weight aminopeptidase inhibitor, was purified to homogeneity from Streptomyces rimosus culture filtrates. The purification procedure included extraction with methanol, followed by chromatography on Dowex 50WX4, AG50WX4, and HPLC RP C18 columns. By amino acid analysis, mass spectrometry, and NMR spectroscopy, the structure of lapstatin was shown to be 3-amino-2-hydroxy-4-methylpentanoylvaline. Lapstatin inhibited the extracellular leucine aminopeptidases from Streptomyces rimosus, Streptomyces griseus, and Aeromonas proteolytica with an IC50 in the range of 0.3-2.4 microM. IC50 values for other enzymes tested were at least tenfold higher. Leucine aminopeptidase from Streptomyces griseus was inhibited in a competitive manner, with an inhibition constant of 5 x 10(-7) M. Lapstatin is the first low-molecular-weight compound isolated from streptomycetes shown to inhibit an autogenous aminopeptidase.

Bacterial Proteins↗

PubMed1984

Induction of DNA polymerase alpha and terminal deoxynucleotidyl transferase in the human lymphoblastoid cell line Molt-4 by the immunomodulator bestatin.

The influence of the immunomodulator bestatin on the expression of terminal deoxynucleotidyl transferase and of DNA polymerase alpha and beta in Molt-4 cells has been studied. Bestatin was found to stimulate cell growth within the range of 0.3-33 microM, while concentrations higher than 300 microM were inhibitory during an incubation period of 48 h. The cell surface bound microsomal leucine aminopeptidase (bestatin receptor) activity decreased gradually during incubation at concentrations of bestatin above 3 microM. This effect was also observed after incubation with amastatin, but not with leupeptin or tunicamycin. Determinations of the activities of DNA synthesizing enzymes from bestatin-treated Molt-4 cells revealed a direct correlation between the decrease of the surface bound microsomal leucine aminopeptidase activity and the increase of the terminal deoxynucleotidyl transferase and DNA polymerase alpha activity; the DNA polymerase beta activity remained unchanged. From these experiments it is hypothesized that bestatin might cause a promoting effect on the differentiation processes of precursor T cells in vivo.

Adjuvants, Immunologic↗

PubMed2002

Saccharomyces boulardii enhances N-terminal peptide hydrolysis in suckling rat small intestine by endoluminal release of a zinc-binding metalloprotease.

Saccharomyces boulardii (S. boulardii), a biotherapeutic agent effective in acute and chronic enterocolopathies, produces trophic intestinal effects at least in part mediated by the endoluminal release of polyamines. However, the effects of the yeast on peptide hydrolysis have not yet been studied. The objectives of this study were to assess in suckling rats the endoluminal and mucosal aminopeptidase activities in response to S. boulardii treatment and to analyze their related mechanisms. Peptidase activities were assayed on yeast cells by using several L-amino acid-p-nitroanilide substrates in the pH range of 2 to 10. A marked hydrolytic activity was found for L-leucine-p-nitroanilide that peaked at pH = 8 (K(m) = 0.334 mM, V(max) = 44.7 micromol.min(-1).g(-1) protein). N-terminal peptide hydrolysis was confirmed using as substrate L-Leu-Gly-Gly (K(m) = 4.71 mM, V(max) = 18.08 micromol.min(-1).g(-1) protein). Enzyme reactions were inhibited in the presence of 1 mM Zn(2+). Oral treatment of sucklings with S. boulardii significantly enhanced jejunal and ileal mucosal leucine-aminopeptidase activities by 24 and 34%, respectively, over controls. In concordance, aminopeptidase activity was enhanced in jejunal and ileal endoluminal fluid samples by 47 and 105%, respectively. By use of an IgG-purified antibody raised against the zinc-binding domain common to metalloproteases, the yeast aminopeptidase was immunoprecipitated and detected as an heteromeric enzyme of 108 and 87-kD subunits. S. boulardii, when given orally to suckling rats, is able to significantly enhance hydrolysis of N-terminal oligopeptides in both endoluminal fluid and intestinal mucosa by the endoluminal release of a leucine aminopeptidase that appears to be a zinc-binding metalloprotease belonging to the M1 family of peptidases.

Amino Acid Sequence↗