Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMINOPEPTIDASES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,297 records · Page 72Linked to original sources
PubMedDate not supplied

Site-directed mutagenesis of leukotriene A4 hydrolase: distinction of leukotriene A4 hydrolase and aminopeptidase activities.

Leukotriene (LT) A4 hydrolase catalyzes enzymatic hydration of LTA4 to biologically active substance, LTB4. Biochemical and immuno-histochemical studies have shown that this enzyme is ubiquitously distributed in various cells and tissues. A sequence domain of LTA4 hydrolase was found to be homologous to those of several zinc metalloproteases. Both native and recombinant enzymes were shown to possess equimolar zinc ion and aminopeptidase activity. To examine the molecular mechanism of this enzyme reaction, site-directed mutagenesis experiments were carried out. Single amino acid substitutions at Glu-297 revealed a distinction of two enzyme activities, and suggest that the glutamic acid residue at 297 is essential for aminopeptidase, while the side chain of Glu or Gln is required for LTA4 hydrolase activity. The loss of two enzyme activities in a mutant E319K confirmed the proposal that the presence of a zinc ion in the enzyme is required for both enzyme activities.

Amino Acid Sequence↗
PubMed1977

[Excretion of alanine aminopeptidase in the urine after administration of lysosomotrophic substances in patients with latent or florid pyelonephritis].

It is described a test for the presence of diffuse nephropathies which is based on the fact that after application 20 ml of the renal diatrizoate X-ray contrast medium Visotrast or of 500 ml of a 10% mannitol solution in patients with preexisting renal diseases appear reversible, diagnostically relevant increases of the alanine aminopeptidase excretion with the urine. In persons with healthy kidneys the excretion of enzymes changes insignificantly. The increased excretion of alanine aminopeptidase is also observed in patients with latent pyelonephritis and is traced back to the increased formation of an osmotic nephropathy in patients with preexisting nephropathies.

Alanine↗
PubMed1996

Biology of Amazonian anopheline. XX. Ontogeny of esterases, leucine aminopeptidase and alpha-glycerophosphate dehydrogenase in Anopheles (Nyssorhynchus) darlingi Root, 1926 (Diptera, Culicidae).

The esterases, leucine aminopeptidase and alpha-glycerophosphate dehydrogenase revealed modifications in gene expressions during the development of Anopheles darlingi. The esterases showed five activity bands, 1 and 2 being more deeply stained during the larval stages than in pupae or adults, esterases 3 and 4 more deeply stained in pupae and adults whereas esterase 5 was present throughout development. Leucine aminopeptidase showed five activity bands: LAP2 and LAP5 were characteristic of larvae, LAP3 was specific for pupae and adults, LAP4 was detected only in pupae, and LAP1 and LAP6 were detected in all stages. alpha-Glycerophosphate dehydrogenase presented one activity band on starch gel whose intensity increased with development. Two activity bands were detected on polyacrylamide gel (alpha-GPDH1 and alpha-GPDH2) in 4th-instar larvae (old pigmented larvae) and this activity increased with development.

Animals↗
PubMed1977

Cytoenzymology of benign and malignant tumours of the corpus uteri. III. Alkaline phosphatase, non-specific esterase and leucine aminopeptidase.

The localization and enzymatic activity of alkaline phosphatase, non-specific esterase and leucine aminopeptidase were studied in normal menopausal corpus uterine tissues and its benign (fibromyoma and cellular fibromyoma) and malignant tumours (endometrium adenocarcinomata and spindle cell sarcoma). Alkaline phosphatase was localized in the cytoplasm and nuclear structures and showed the highest intense activity in well-differentiated papillary adenocarcinoma. Non-specific esterase was confined to the cytoplasm and was particularly marked in undifferentiated adenocarcinoma cells. Leucine aminopeptidase was considerably higher in spindle cell sarcoma than endometrium adenocarcinoma. Generally, the aforementioned enzymes were increased in neoplastic tumour tissues of the uterus than the homologous normal tissues.

Alkaline Phosphatase↗
PubMed1996

Basic aminopeptidase from rabbit kidney: purification and partial characterization.

The aminopeptidase activity of a homogenate of rabbit kidney treated with Triton X-100 was measured using L-aminoacyl-2-naphthylamides (AA-NA). After gradient elution ion-exchange chromatography, four peaks of aminopeptidase activity were eluted. The enzyme eluted at 450 microS containing 33.5% of the activity towards Arg-NA was applied to a Superdex 75 column and presented only one protein band on 10% SDS-polyacrylamide gel electrophoresis. This enzyme has an apparent molecular mass of 78 kDa, is five-fold activated by 0.15 M NaCl and the highest Vmax/KM ratio was obtained with Arg-NA. Enzyme activity was inhibited 100% by 0.13 mM sodium p-hydroxymercuribenzoate, 20% by 0.75 mM EDTA and 100% by 0.66 mM o-phenanthroline. Puromycin and bestatin behaved like competitive inhibitors with a Ki of 0.60 mM and 5.0 microM and 5.0 microM, respectively.

2-Naphthylamine↗
PubMedDate not supplied

[Aminopeptidases in cells of non-Hodgkin's lymphoma of varying degrees of malignancy and in lymphogranulomatosis].

26 cases of lymphoproliferative diseases were studied: 8 cases of reactive follicular hyperplasia (RFH), 11 cases of non-Hodgkin's malignant lymphomas (NML), 7 cases of lymphogranulomatosis (LGM). Only gamma-glutamyl transpeptidase (GGT) was found in lymphoid cells of B- and T-dependent areas of lymph nodes with reactive changes as well as in tumor cells of NML and LGM. GGT activity was more pronounced in NML of high-grade malignancy (centroblast and immunoblast) as compared to lymphomas of lower grade of malignancy (lymphocytic, centroblast-centrocytic and in Lennert lymphoma). GGT activity in cells of Hodgkin and Berezovsky-Sterberg in some cases of LGM was high, in others low. Significant differences in GGT activity between RFH and follicular centroblast-centrocytic lymphoma were not found. Activity of aminopeptidase M was observed in histiocytes, fibroblasts, vessels and areas of connective tissue growth. Aminopeptidase A activity was observed in vessels only. Activity of dipeptidyl(amino)peptidase IV was observed in some lymphoid cells in RFH, NML and LGM. Thus, GGT activity may be considered as a differential-diagnostic marker in separating NML of high and low degree of malignancy and this may presume a different sensitivity to the therapy.

Aminopeptidases↗
PubMedDate not supplied

An aminopeptidase regulates LPS stimulated interleukin-8 receptor on the surface of human neutrophils.

A large number of inflammatory diseases are mediated by interleukin-8, an inflammatory neutrophil chemotactic agent. Since the cytokine acts through a cell surface receptor, detailed knowledge about the regulation of receptor expression is very important. We found that LPS in serum became activated and triggered the expression of IL-8 receptor by more than two folds within 30 min. After that period, the receptor attained normal level within 2 hr of SA-LPS stimulation. EDTA and bestatin could block this downregulation of IL-8 receptor. Intracellular Ca2+ level was increased till 45 min of SA-LPS stimulation and then the level was reduced. Addition of CaCl2 accelerated and depletion of Ca2+ inhibited the downregulation of the IL-8 receptor. The ligand could fully protect the loss of receptor from downregulation. It suggests that during SA-LPS stimulation, increase in intracellular Ca2+ level activates an aminopeptidase which presumably cleaves the N-terminal region of the receptor, critically essential for the function of IL-8. Thus the activated aminopeptidase regulates the functions of IL-8. The study is important for understanding the regulation of IL-8 receptor expression by LPS during bacterial infection.

Aminopeptidases↗
PubMed1998

Characterization and partial purification of a leucine aminopeptidase from Fasciola hepatica.

An aminopeptidase activity capable of hydrolyzing different aminomethylcoumarin amino acids, but mainly leucine-7-amino-4-methylcoumarin (Leu-NHMc), was detected in deoxycholic soluble extracts from adult Fasciola hepatica. The enzyme (EC 3.4.11.1) was partially purified by gel filtration and EAH-Sepharose affinity chromatography using bestatin as a ligand. Results obtained by gel filtration, direct fluorogenic substrate analysis in polyacrylamide gel, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggest that in a native form the enzyme might be aggregated as a high molecular weight complex. By affinity chromatography on concanavalin A Sepharose, the enzyme did not bond to the column showing that it lacks mannose residues. The F. hepatica aminopeptidase was characterized as a metalloproteinase based on its activation by Mn2+ and Mg2+, and its inhibition by EDTA, 1,10-phenanthroline, and bestatin. It has an optimal activity at a pH between 8.0 and 8.5. Histochemical localization revealed strong leucine naphthylamidase activity at the cells lining the gut epithelium of the parasite.

Animals↗
PubMed1976

[Alanine aminopeptidase and creatinine excretion under various conditions of diuresis in man].

In 10 female test persons Volhard's water and concentration experiment was carried out. It exists a highly significant correlation between the alanine aminopeptidase activity and the creatinine concentration in the urine. The relation of the two factors to the urine minute volume is hyperbolic. The creatinine in the urine may be regarded as a favourable reference parameter for the excretion of alanine aminopeptidase.

Adult↗
PubMed1976

[Affinity labeling of leucine aminopeptidase with new substrate analog inhibitors].

Substrate analogous compounds differing both in type and reactivity (diazonium group, chloro and mo ethyl ketone groups) and in the position of the reactive group at the inhibitor molecule were studied for their adequacy for affinity labelling of leucine amino-peptidase. The chloro methyl ketone derivatives of amino acids with free alpha-amino group are competitive inhibitors. Also, the more reactive bromine compound PheCh2br (Ki 1.2 mM) compared with the PheCH2C1 (Ki 0.3 mM) fails to give an irreversible inactivation of leucine amino-peptidase. The dipeptide derivatives Leu-PheCH2C1 and Phe-LeuCH2C1 also inhibit the enzyme activity up to 65%, but they are split at the peptide bond under reactivation of the enzyme. p-Diazophenylalanine methylketone Phe (pN+/2)CH3 and the two dipeptides Phe(pN+/2)-Phe and Phe(pN+/2)-Phe(pN+/2) with N-terminal diazonium groups afford an irreversible inactivation of leucine aminopeptidase in a time- and concentration-dependent reaction. The Phe-Phe(pN+/2) reactive only C-terminally, is less effective; the inhibition is partly reversible. The inactivation is strongly reduced by the competitive inhibitor Thr(but)-Phe-Pro. These effects are discussed with regard to the specific site of attack of the inhibitors in the active binding centre of leucine aminopeptidase. The synthesis of the three parasubstituted amino derivatives of phenylalanyl-phenylalanine Phe(pNH2)-Phe, Phe-Phe(pNH2) and Phe(pNH2)-Phe(pNH2) and their selective conversion to the respective diazonium peptides, retaining the aliphatic alpha-amino group, are discussed.

Affinity Labels↗
PubMed1976

[Influence of glutathione on the catalytic properties of leucine aminopeptidase].

1. Leucine aminopeptidase does not catalyze the hydrolysis of glutathione. 2. Glutathione inhibits the hydrolysis of the substrates leucine hydrazide and leucine-p-nitroanilide by leucine aminopeptidase. 3. By means of kinetic experiments the type of the inhibition has been determined as noncompetitive. The inhibition constant Ki for the Mg2+-activated enzyme is five times higher than for the non-activated enzyme. 4. The degree of inhibition caused by glutathione depends on the pH value indicating a competition between glutathione and OH- ions. Mg2+-activated enzyme is invariably inhibited in the investigated pH range of 7.2 to 9.8. 5. A preincubation of the enzyme with glutathione changes the degree of activity enhancement by metal ions.

Animals↗
PubMed1991

Aminopeptidase A in human placenta and pregnant serum.

The activities of serum aminopeptidases (APs) derived from the placenta rise during pregnancy. To confirm the localization of AP-A, which liberates N-terminal acidic amino acids, in placental tissue and to identify it in the serum of pregnant women, chromatographic separation was performed. When a placental extract was subjected to DEAE cellulose column chromatography, the Glu-MCA degradative activity, or AP-A, was separated into two entities. Inhibition testing revealed that the enzyme eluted in Fraction No. 20 from the DEAE-cellulose column consisted of typical AP-A with a molecular weight of approximately 500,000. When the Glu-MCA degradative activity was observed by filtering pregnant serum through HPLC TSK G3000 gel, the activity was found to be due to serum CAP rather than AP-A. What had been thought to be a biochemicophysiological action inherent in blood AP-A raised additional questions.

Aminopeptidases↗
PubMed2004

Diagnostic applicability of dipeptidyl aminopeptidase IV activity in cytological samples for differentiating follicular thyroid carcinoma from follicular adenoma.

HYPOTHESIS: Dipeptidyl aminopeptidase IV (DPP IV) activity in cytological samples from a follicular thyroid tumor is the most sensitive and specific indicator for the detection of follicular carcinoma of the thyroid gland. Dipeptidyl aminopeptidase IV activity is independent of cytological characteristics and superior to other clinical findings. DESIGN AND PATIENT SELECTION: Among the patients surgically treated for follicular thyroid tumors, we recruited approximately equal numbers of those with true-positive (n = 19), true-negative (n = 26), false-negative (n = 16), and false-positive (n = 18) cytological characteristics. MAIN OUTCOME MEASURES: We examined DPP IV activity using cytological specimens obtained from 35 patients with follicular thyroid carcinomas and 44 patients with follicular adenomas. Tumor size, patient age, serum thyroglobulin level, and ultrasonographic findings were also analyzed. RESULTS: The positive rate of DPP IV activity was 97% in 35 patients with follicular thyroid carcinomas and 5% in 44 patients with follicular adenomas, resulting in a sensitivity of 97%, a specificity of 95%, and an overall accuracy of 96%. This discriminating ability of DPP IV activity was far higher than that of tumor size, patient age, serum thyroglobulin level, or ultrasonographic findings. CONCLUSIONS: Positive DPP IV activity in cytological samples is the best discriminatory marker between follicular thyroid carcinoma and follicular adenoma. Its application could alter the clinical management of patients with follicular thyroid tumors.

Adenocarcinoma, Follicular↗
PubMed1996

Activity of neutral endopeptidase and aminopeptidase N in mouse thymic stromal cells which bind double-positive thymocytes.

The activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T-TG-St) was grown from transgenic mouse expressing temperature-sensitive SV40 T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP-TG-St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double -positive cell-binding stroma exhibited strong activity of two peptidases, neutral endopeptidase (NEP; EC 3.4.24.11) and aminopeptidase N (APN; EC 3.4.11.2). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of the specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double-positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes.

Amino Acid Sequence↗
PubMed2002

Quaternary benzo[c]phenanthridine alkaloids as inhibitors of aminopeptidase N and dipeptidyl peptidase IV.

Chelerythrine, sanguinarine and an alkaloid extract from Macleaya cordata--sanguiritrin--were found to be inhibitors of aminopeptidase A and dipeptidyl peptidase IV, while fagaronine inhibited dipeptidyl peptidase IV only. At 50 microM, chelerythrine, sanguinarine and sanguiritrin inhibited aminopeptidase N by 82%, 82%, 88%, DPP IV by 38%, 62%, 57%, and fagaronine by 34%, respectively. When bovine serum albumin (500 microg/mL) was added, the inhibition of both proteases by quaternary benzo[c]phenanthridine alkaloids (QBA) (50 microM) was significantly diminished. Strong interaction of chelerythrine and sanguinarine with bovine and human serum albumin was proved by electrophoretic determination of their respective conditional binding constants.

Alkaloids↗
PubMed1994

Isolation and DNA sequence of the STE13 gene encoding dipeptidyl aminopeptidase.

We have isolated a mutant which exhibits partial constitutivity for a-specific gene expression in alpha cells. The wild-type gene was cloned and demonstrated to be allelic to the STE13 gene, which encodes the dipeptidyl aminopeptidase involved in processing of the alpha-factor prepropheromone. Thus, the mating defect of the ste13 mutations in alpha cells may result both from the production of incompletely processed alpha-factor and from the increased expression of a-specific genes. The STE13 open reading frame of 931 amino acids contains a putative membrane-spanning segment near its amino terminus and is 31% identical to a second yeast dipeptidyl aminopeptidase (DAP2). A null mutant of STE13 has been constructed: it is viable and sporulation-proficient.

Amino Acid Sequence↗
PubMed1994

Na(+)-dependent transport of aminopeptidase-resistant sugar-coupled tripeptides in rat intestine.

Aminopeptidase-degradable tripeptide, tyrosylglycylglycine (TGG, a part of aminopeptidase-degradable enkephalines), was coupled with sugars (cellobiose, maltose, lactose, gentiobiose and glucose). These sugar-coupled TGGs were stable enough to be transported from the mucosal to the serosal side in rat everted small intestine, while TGG was not stable enough to be transported. The transport of sugar-coupled TGGs was decreased in the absence of Na+, indicating the Na(+)-dependent transport of sugar-coupled TGG in rat intestine. Cellobiose-coupled TGG and glucose-coupled TGG did not mutually inhibit their transport. It was suggested that the intestinal Na(+)-dependent transporter for disaccharide-coupled tripeptides, which have a pyranose ring, was different from that of monosaccharide-coupled tripeptide, which has no pyranose ring.

Amino Acid Sequence↗
PubMed1999

N-acetylgalactosamine on the putative insect receptor aminopeptidase N is recognised by a site on the domain III lectin-like fold of a Bacillus thuringiensis insecticidal toxin.

Binding of the insecticidal Bacillus thuringiensis Cry1Ac toxin to the putative receptor aminopeptidase N is specifically inhibited by N-acetylgalactosamine (GalNAc), suggesting that this toxin recognises GalNAc on the receptor. A possible structural basis for involvement of domain III of the toxin in carbohydrate-mediated receptor recognition was noted in the similarity between the domain III fold of the related toxin Cry3A and a carbohydrate-binding domain in the 1,4-beta-glucanase from Cellulomonas fimi. This possibility was investigated by making selected mutations in domain III of the Cry1Ac delta-endotoxin. Mutagenesis of residues Asn506, Gln509 or Tyr513 resulted in toxins with reduced binding and a slower rate of pore formation in Manduca sexta midgut membrane vesicles compared to the wild-type Cry1Ac. These mutants also showed reduced binding to the 120 kDa Cry1Ac putative receptor aminopeptidase N. Unlike the wild-type toxin, binding of the triple mutant N506D,Q509E,Y513A (Tmut) to M. sexta midgut membrane vesicles could not be inhibited by GalNAc. These data indicate that GalNAc binding is located on domain III of Cry1Ac and therefore support a lectin-like role for this domain. A preliminary analysis of the Cry1Ac crystal structure locates Asn506, Gln509 and Tyr513 in a region on and adjacent to beta-16 in domain III, which has a unique conformation compared to the other known Cry structures. These residues are in a favourable position to interact with either soluble or protein-bound carbohydrate.

Acetylglucosamine↗