Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme present in mouse brain cytosol cleaves C-terminal dipeptides from substrates including ACTH-(7-10) (Phe-Arg-Trp-Gly), and des-Tyr-[Met]- and des-Tyr-[Leu]enkephalin. By means of ion-exchange chromatography and gel filtration, the peptidase was purified to a specific activity of 1570 times that of brain homogenate. At this purification, a second peptidase, which hydrolyzes Trp-Gly and other peptides [M. E. A. Reith and A. Neidle (1979) Biochem. Biophys. Res. Commun. 90, 794-800] was still present, but could be removed by preparative polyacrylamide gel electrophoresis. The des Tyr-enkephalin-cleaving enzyme has a molecular weight of about 85,000 and a pH optimum of 7.8. It is inhibited by metal-chelating and sulfhydryl reagents. The enzyme has a strong preference for substrates with an aromatic residue in the position adjacent to the C-terminal amino acid, although some peptides meeting this criterion were competitive inhibitors rather than substrates. Peptides with less than four residues were inactive and, in general, tetrapeptides were found to be more reactive than larger analogs, when peptides with common C-terminal sequences were compared. The peptidyl dipeptidase, which has not been described previously, can be readily distinguished from angiotensin-converting enzyme (EC 3.4.15.1) and from neutral endopeptidase (EC 3.4.24.11) by its subcellular localization, substrate specificity, and response to inhibitors. It was suggested that peptidyl dipeptidase-B (PDP-B, EC 3.4.15.-) would be an appropriate name for the enzyme. PDP-B is widely distributed among mouse tissues.
 ...
PMID:The isolation of a peptidyl dipeptidase from mouse brain cytosol that cleaves adrenocorticotropic hormone-(7-10) and des-tyrosine-enkephalins. 608 38

Endopeptidase-24.11 (EC 3.4.24.11) from pig kidney hydrolysed CCK-8 (sulphated) at two distinct sites: Asp-Tyr(SO3H)-Met-Gly Trp-Met-Asp PheNH2. Under initial conditions, the splitting of the Asp7-Phe8NH2 bond proceeded 4-times more rapidly than the Gly4-Trp5 bond. Pig brain striatal synaptic membranes attacked this substrate at the same sites and this activity was inhibited by phosphoramidon. However, other products were detected even in the presence of phosphoramidon. One of these products was identified as free tryptophan. Since their formation was inhibited by bestatin, one or more membrane aminopeptidases is also implicated in the degradation of CCK-8.
 ...
PMID:Endopeptidase-24.11 and aminopeptidase activity in brain synaptic membranes are jointly responsible for the hydrolysis of cholecystokinin octapeptide (CCK-8). 609 Feb 6

Neutral thiol-activated peptidases present in the pH 5-soluble fraction of rabbit brain (separated by step-elution chromatography on diethylaminoethyl cellulose) were screened for the hydrolysis of bradykinin. Lys-bradykinin, Met-Lys-bradykinin, angiotensin I, angiotensin II, substance P, luteinizing hormone-releasing hormone (LH-RH), and neurotensin by bioassay. The column effluent was monitored for bradykinin inactivation and arylamidase activity and combined in six pools on the basis of bradykinin inactivation. The pools were characterized by determining the peptide fragments and amino acids released from bradykinin with an amino acid analyzer. Pools 1 through 3 contained 80% of the kininase activity and essentially all of the endopeptidase A and B activity, whereas pools 4 through 6 accounted for 98% of the recovered arylamidase activity. Bradykinin, angiotensin I, angiotensin II, and substance P were inactivated by all the pools, whereas LH-RH and neurotensin were inactivated by pools 3 and 4, and pools 3, 4, and 5, respectively. These data show that rabbit brain contains peptidases having some selectivity for the inactivation of neuropeptides. Endopeptidase B purified from pool 3 is inhibited by bradykinin-potentiating peptide 9a (BPP9a, SQ 20881) (< Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro), a competitive inhibitor of the hydrolysis of bradykinin (Km = 3.5 X 10(-5) M, Ki = 3 X 10(-6) M) which also completely inhibits the inactivation of LH-RH.
 ...
PMID:Screening for rabbit brain neuropeptide-metabolizing peptidases. Inhibition of endopeptidase B by bradykinin potentiating peptide 9a (SQ 20881). 616 Dec 9

Membrane-bound neutral metalloendopeptidase ("enkephalinase") was purified from rabbit brain and compared with a homogeneous preparation of a similar enzyme (EC 3.4.24.11) isolated from rabbit kidney. The two enzymes had the same pH optimum and the same apparent molecular weight. They showed identical specificity toward several synthetic substrates and cleaved both Met- and Leu-enkephalin at the Gly-Phe bond. Minor, but significant, differences were found between the two enzymes in the inhibitory constants determined for phosphoramidon and the N-[1(R,S)-carboxy-2-phenylethyl] derivatives of phenylalanyl and alanyl-p-aminobenzoate. A guinea pig antiserum obtained against the rabbit kidney enzyme showed strong crossreactivity with the rabbit brain enzyme when tested in an anticatalytic immunoinhibition assay. Ouchterlony immunodiffusion experiments gave a pattern of precipitation consistent with partial identity of the two enzymes. The kidney enzyme, however, seemed to contain antigenic determinants not present on the brain enzyme. The data indicate that the two enzymes are identical with respect to specificity, pH optimum, and molecular weight, but show minor, although significant, differences in interaction with active-site-directed inhibitors and specific antisera.
 ...
PMID:Biochemical and immunological properties of a membrane-bound brain metalloendopeptidase: comparison with thermolysin-like kidney neutral metalloendopeptidase. 641 77

The heptapeptide Met-enkephalin-Arg6-Phe7 (MERF) and the octapeptide Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) are potent opioid peptides present in the sequence of proenkephalin, the common precursor of Met- and Leu-enkephalin (ME and LE). We demonstrate that MERF and MERGL are released concomitantly with ME and LE from rat striatal slices following a depolarisation by K+. This release is a Ca2+-dependent process. While the ratios of ME to LE, MERF and MERGL found in the tissue (ME/LE = 2.6; ME/MERF = 3.1; ME/MERGL = 4.5) are in good agreement with the ratios found in the proenkephalin molecule (ME:LE:MERF:MERGL = 4:1:1:1), the amounts of MERF and MERGL recovered from the medium are low compared to those of ME and LE, suggesting a rapid degradation of released MERF and MERGL. In fact, when incubated with striatal slices, (3H-Tyr)-MERF is rapidly degraded by four classes of peptidases: the "enkephalinase", the angiotensin-converting enzyme (ACE), aminopeptidase(s) and an endopeptidase releasing the tetrapeptide Tyr-Gly-Gly-Phe (YGGF). Whereas the activities of the three former peptidases are reduced or abolished in the presence of thiorphan (0.1 microM), captopril (1 microM) and bestatin (20 microM), the amount of YGGF formed by the endopeptidase is not reduced in these conditions but actually increased.
 ...
PMID:Release of the heptapeptide Met-enkephalin-Arg6-Phe7 and of the octapeptide Met-enkephalin-Arg6-Gly7-Leu8 from rat striatum in vitro and their rapid inactivation. 666 13

An enzyme capable of converting putative opioid peptide intermediates to free enkephalin has been purified 300-fold from washed rat brain membranes. The action of this enzyme, an enkephalin-generating endopeptidase (EGE), was compared with the action of carboxypeptidase B after trypsin treatment on enkephalin precursor peptides present in rat striata. After Sephadex G-100 gel filtration of striatal material, fractions were radioimmunoassayed for enkephalin content using an antiserum specific for the carboxyl terminal of enkephalin. Additionally, aliquots of the column fractions were treated with either trypsin and carboxypeptidase B, trypsin and EGE, or EGE alone. The peak of enkephalin immunoreactivity increased with the enzymes' treatment indicating the conversion of the low molecular weight proenkephalin precursor peptides to enkephalin. Trypsin and EGE generated almost as much enkephalin as trypsin and carboxypeptidase B in the conditions of the experiment. Thus EGE is capable of processing precursors to enkephalin after the action of trypsin-like enzyme(s) in the brain. The gel filtration fractions containing enkephalin and its low molecular weight precursors were pooled and one-half treated with EGE. The contents were analyzed by HPLC and the increase in immunoreactivity co-eluted with enkephalin and Leu-enkephalin. Small peptides found to be the most potent competitive inhibitors of this enzyme are Met-Arg-Phe-Ala, and Met-Arg-Phe.
 ...
PMID:Brain endopeptidase generates enkephalin from striatal precursors. 675 May 68

N alpha-Acyl amino acid releasing enzyme (NAARE), an enzyme cleaving acetylMet-Ala at the Met-Ala bond was purified from rat brain cytosol to apparent homogeneity by salt precipitation, gel filtration, and several steps of ion exchange. Levels of NAARE exceeded acylase measured with acetylmethionine in all brain regions and subcellular fractions examined: 60% was associated with cytosol and the remainder with debris or the crude nuclear and mitochondrial-synaptosomal subfractions. Activity was highest in pituitary and was approximately 0.5-0.6 that of liver or kidney. The purified enzyme preferentially hydrolyzed acetylmethionyl peptides: Km for acetylMet-Ala was 0.93; Vmax, 3.5 nmol-1 (kcat, 1185) with pH optimum of 8.9 as compared with 8.2 for acylases measured in cytosol. The purified enzyme was devoid of acylase and common exo- and endopeptidase contamination. Structure-activity relationships examined with synthetic formylated or acetylated peptides indicated no significant effects for di- or tripeptides if the second substituent was Ala, Ser, Asn, or Thr, but the activity was reduced 0.5-fold for Leu, a branched-chain amino acid. No hydrolysis was observed for polypeptides with five or more residues having N-terminal acetylated Tyr (enkephalin) or Ser (alpha-melanocyte-stimulating hormone, thymosin alpha 1), supporting the notion that the enzyme plays a role only in turnover of smaller peptides formed perhaps as a result of endopeptidase cleavage of proteins or polypeptides containing acetylated Met at the N terminus.
 ...
PMID:Observations on N alpha-deacetylation of model amino acids and peptides: distribution and purification of a specific N-acyl amino acid releasing enzyme in rat brain. 686 20

Two distinct enzymatic activities capable of hydrolyzing enkephalin are present in the brain. The major activity was shown to be a neutral aminopeptidase which hydrolyzes Leu-enkephalin (Leu-Enk) with a Km of 2 X 10(-5) M. This activity was inhibited by heavy metal ions (i.e. Zn++, Cd++), by sulfhydryl blocking reagents, and by the antibiotics bacitracin and puromycin. In contrast, these two antibiotics had no effect on the hydrolysis of Leu-Enk by either rat serum or commercial leucine aminopeptidase. The integrity of both the glycosidic and peptide bonds in the puromycin molecule was required for its inhibitory activity. On the other hand, modifications of the sugar moiety had relatively little effect, allowing the design of puromycin analogs which were inactive with regard to protein synthesis inhibition but still capable of inhibiting brain aminopeptidase. Puromycin was also shown to inhibit enkephalin degradation by homogenates of guinea pig ileum and to prolong the depressant effect of enkephalin on the electrically induced contractions of the ileum. The second enzymatic activity in brain homogenate was found to sediment with the synaptic plasma membrane fraction and cleave Leu-enkephalin into Tyr-Gly-Gly and Phe-Leu with a Km of 2.2 X 10(-5) M and pH optimum between 6.5 and 7.0. This endopeptidase was inhibited by metal chelating agents and by thiols but was insensitive to puromycin and to p-chloromercuribenzoate. In contrast to the aminopeptidase some cleavage of (D-Ala2)Met-Enk x amide by the endopeptidase was observed.
 ...
PMID:Inactivation of enkephalin by brain enzymes. 700 99

The usefulness of optimized and newly elaborated histochemical methods for proteinases is illustrated on two selected substances. DAP IV (Gly-Pro-MNA,FBB,pH 7.2) was discovered in 39% and DAP II (Lys-Ala-MNA,FBB,pH 5.5) in 60% of the lymphocytes of human peripheral blood (ly). The reaction product of such ly differs in quality and quantity. On the ultrastructural level, the reaction product of DAP IV (Gly-Pro-MNA,HNF) was found in cell membranes and lysosomes. Enzyme activity in other areas was probably suppressed during the preparation procedure. Although the number of ly revealed with Lys-Pro-MNA and Phe-Pro-MNA at pH 5.5 and with Lys-Pro-MNA at pH 7.2 is high, these substrates do not distinctly discriminate DAP IV and DAP II. DAP IV occurs exclusively in T lymphocytes. The number of DAP IV-positive ly was not decreased in patients with myelofibrosis, plasmacytoma, chronic granulocytic leukemia, or tricholeukemia. It was, however, greatly reduced in chronic lymphatic leukemia (CLL). In patients with malignant lymphomas other than CLL, ly presence is related to the stage of the disease. Decreased values indicate a more severe stage or a relapse. In the majority of patients with gastric cancer DAP IV-positive ly were decreased. They were normal or increased in patients with peptic ulcer. The assessment of the number of DAP IV-positive ly is a simple method that provides information regarding the condition of patients with malignant lymphomas and gastric carcinoma. Neutrophilic leukocytes and their precursors, and to a lesser extent monocytes, are revealed when N-acetyl-Met-I-naphthyl ester (Ac-Met-N) is used as substrate. Membrane-bound lysosomal and cytosol proteinases were investigated together with disaccharidases in jejunal biopsies of patients with malabsorption syndrome. Activities of all enzymes were affected in patients with celiac disease. According to their impairment enzymes could be arranged: Lactase(L). trehalase (T), brush border endopeptidase (BBEP), gamma-glutamyl transferase (GGT), DAP IV, enzyme(s) cleaving Ac-Mer-N, aminopeptidase A, cytosol peptidases and aminopeptidase M. In the propria, DAP IV is decreased or absent, while GGT and, particularly, DAP II are increased. After a gluten-free diet, activities are restored in a reverse order. BBEP and GGT are useful as auxiliary parameters in the assessment of the damage or differentiation degree of enterocytes. DAP IV is a sensitive indicator of the involvement of the propria.
 ...
PMID:Proteinases in pathology. Usefulness of histochemical methods. 701 84

The present study was performed to investigate the enzymatic changes in dystrophic chickens compared to those of dystrophic mice. The activities of 14 kinds of aminopeptidases, 5 kinds of endopeptidase, 4 kinds of glycosidases, phosphatase, esterase, and ribonuclease were measured in muscles of control and dystrophic chickens. When the enzyme activities were expressed as specific activity per unit weight of organs, only some of them were found to be significantly elevated in dystrophic chickens; e.g., alanine aminopeptidase (Ala-AP), Gly-AP and cathepsin D. On the contrary, the activities of alpha-D-glycosidase, alpha-D-galactosidase and alpha-D-mannosidase were significantly decreased. Muscular protein contents of dystrophic chickens also tended to be lower than those of controls. These observations offer a striking contrast with the one obtained in the study on dystrophic mice. However, when expressed as specific activity per mg protein, many enzyme activities were found to be significantly elevated suggesting an extensive abnormality of metabolism in dystrophic chickens. Among 14 kinds of aminopeptidase activities, highly significant elevations were seen especially in AP-A, AP-B, Gly-AP, Ala-AP, Ser-AP, Pro-AP, Leu-AP, Met-AP and Trp-AP. Interestingly enough, a statistical approach suggested a significant correlation between the aminopeptidase changes of dystrophic chickens with those of dystrophic mice. In addition to aminopeptidases, there were highly significant increases in the activities of cathepsin D, alpha-D-glucosidase, beta-D-galactosidase, alpha-D-mannosidase, esterase and RNase. These results indicate that the intramuscular metabolic abnormality of dystrophic chickens are generally different from but partly resembled with those of dystrophic mice.
 ...
PMID:Intramuscular enzyme abnormalities of dystrophic chickens compared to those of dystrophic mice. 701 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>