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)

Less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, the luteinizing hormone-releasing hormone, LHRH, is degraded in renal proximal tubules (PT) in vivo (rat) and in vitro (rabbit) to less than Glu-His (2), less than Glu-His-Trp (3), and less than Glu-His-Trp-Ser (4). LHRH may be cleaved by endopeptidases simultaneously at multiple bonds, or initially at Ser4-Tyr5 followed by carboxypeptidase hydrolysis of 4 to 3 and then 2. To distinguish between these mechanisms, [3H]LHRH analogues were incubated with rabbit renal brush-border membranes (BBM), microinfused into PT in vivo or in vitro, and products were analyzed by HPLC. [D-Ser4]LHRH was not cleaved at D Ser4-Tyr5 but yielded less than Glu-His-Trp-D-Ser-Tyr-Gly as the major metabolite plus 2 and 3. [D-Trp6]LHRH was cleaved by BBM and PT to 2 and 3, but not to 4. [D-Ser4, D-Trp6]LHRH was not cleaved by BBM, but was degraded to 2 by PT in vivo. Thus, D-amino acid substituents altered the expected cleavage pattern of these analogues. [3H]LHRH was cleaved by BBM or by endopeptidase-24.11 from porcine PT to metabolites 2, 4, small amounts of 3, and less than Glu-His-Trp-Ser-Tyr-Gly, but cleavage was strongly inhibited by the specific inhibitor phosphoramidon. Thus, normally LHRH may be cleaved in PT by endopeptidase-24.11 to 2 and 4, and by angiotensin I-converting enzyme to 3, its known cleavage site.
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PMID:Effects of D-amino acid substituents on degradation of LHRH analogues by proximal tubule. 354 29

In order to evaluate the structural/functional roles of Met residues in an octadecapeptide pigment-dispersing hormone (PDH: Asn-Ser-Gly-Met-Ile-Asn-Ser-Ile-Leu-Gly-Ile-Pro-Arg-Val-Met-Thr-Glu-Ala- NH2), first described as light-adapting distal retinal pigment hormone (DRPH) from Pandalus, three analogs were synthesized: Nle4-PDH, Nle15-PDH, and Nle4,15-PDH. When tested for melanophore pigment-dispersing activity in destalked Uca, all three Nle-analogs were more potent than unsubstituted PDH. Performic acid oxidation caused a marked loss of potency of PDH, Nle4-PDH, and Nle15-PDH. The analog Nle4,15-PDH was resistant to oxidation and displayed 6-fold higher potency than PDH. Thus Met4 and Met15 are not essential for the PDH activity. The oxidation-induced loss of activity of unsubstituted PDH may result from introduction of oxygen (in methionine sulfone) and a consequent conformational change in the octadecapeptide.
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PMID:Substitution of norleucine for methionine residues in a crustacean pigment-dispersing hormone. 384 Aug 88

This study deals with the effect of deamidation and C-terminal truncation on the potency of an octadecapeptide pigment-dispersing hormone (PDH: Asn-Ser-Gly-Met-Ile-Asn-Ser-Ile-Leu-Gly-Ile-Pro-Arg-Val-Met-Thr-Glu-Ala- NH2), first described as light-adapting distal retinal pigment hormone (DRPH) from Pandalus borealis. Bioassay of synthetic analogs for melanophore pigment dispersion in destalked fiddler crabs (Uca pugilator) showed that deamidation causes a 300-fold decrease in potency. The analogs 1-17 NH2 and 1-16 NH2 were about 3 times more potent than 1-18-OH. Further truncation led to decreases in potency, with the peptide 1-9-NH2 being the smallest C-terminal deletion analog to display activity (0.001% potency). Smaller analogs (1-8-NH2, 1-6-NH2 and 1-4-NH2) were inactive when tested in doses as high as 500 nmoles/crab. On the basis of our earlier work on N-terminal deletion analogs and the present findings the residues 6 to 9 seem to be important for PDH action.
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PMID:C-terminal deletion analogs of a crustacean pigment-dispersing hormone. 384 33

The tripeptide Tyr-Gly-Gly, a hydrolysis product of enkephalins and related opioid peptides obtained with 'enkephalinase', was identified and quantified in various regions of mouse brain by means of HPLC and a sensitive and specific radioimmunoassay. Similar levels i.e. about 8 pmol/brain were found after the animals were killed by various procedures, including microwave irradiation, suggesting its pre-mortem formation. The distribution of Tyr-Gly-Gly immunoreactivity among brain regions was highly heterogeneous and paralleled to a certain extent the [Met5]enkephalin distribution, molar levels of Tyr-Gly-Gly representing 10-30% of those of the enkephalin. Following gentle homogeneisation of striata in 0.32 M sucrose and centrifugation, 73% of Tyr-Gly-Gly immunoreactivity was recovered in the supernatant, a result consistent with its extracellular localisation in vivo. Administration of enkephalinase inhibitors rapidly elicited marked decrease in Tyr-Gly-Gly immunoreactivity whereas bestatin, an aminopeptidase inhibitor, elicited 100% increase and captopril, an ACE inhibitor, was without significant effect. These data indicate that the tripeptide is in a dynamic state in the brain and that its levels might reflect the release of endogenous enkephalins or related opioid peptides and their subsequent metabolism by enkephalinase.
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PMID:Study of endogenous Tyr-Gly-Gly, a putative enkephalin metabolite, in mouse brain: validation of a radioimmunoassay, localisation and effects of peptidase inhibitors. 391 94

Primary roots of soybean [Glycine max (L.), cv Harosoy 63] seedlings were inoculated with zoospores from either race 1 (incompatible, host resistant) or race 3 (compatible, host susceptible) of Phytophthora megasperma f. sp. glycinea (Pmg) and the activities of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), isoflavone synthase, and dihydroxypterocarpan 6a-hydroxylase related to phytoalexin (glyceollin) biosynthesis, and of glucose-6-phosphate dehydrogenase (Glc-6-PDH) and glutamate dehydrogenase (Glu-DH) were determined at various times after inoculation. About 2-4 h after inoculation with race 1, the activities of PAL, CHS, and pterocarpan 6a-hydroxylase were higher than after inoculation with race 3 and increased considerably thereafter. In contrast, activities of these enzymes in the compatible interaction were equal to or only slightly higher than in the controls over the entire infection period investigated (2-8 h). Isoflavone synthase did not increase until 7 h after inoculation with race 1. There were no significant differences in activities for Glc-6-PDH and Glu-DH between inoculated roots and controls. The results show that infection of soybean roots with zoospores of Pmg race 1 causes a race:cultivar-specific early induction of enzymes involved in glyceollin synthesis, whereas such an induction does not occur with zoospores of race 3. These findings are in agreement with the race:cultivar-specific accumulation of glyceollin in soybean roots reported previously [M. G. Hahn, A. Bonhoff, and H. Grisebach (1985) Plant Physiol. 77, 591-601].
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PMID:Race:cultivar-specific induction of enzymes related to phytoalexin biosynthesis in soybean roots following infection with Phytophthora megasperma f. sp. glycinea. 396 19

Cathepsins M and B from rabbit liver lysosomes were separated by chromatography on Ultrogel AcA34 at low ionic strength and purified to homogeneity, and their catalytic and molecular properties were compared. Cathepsin M was relatively inactive with synthetic peptide substrates. Thus, it hydrolyzed benzoyl arginine naphthylamide at only one-fifth the rate observed with cathepsin B, and no activity was detected with Gly-Phe naphthylamide which is a relatively good substrate for cathepsin B. On the other hand, cathepsin M exhibited a preference for protein substrates. It was more active than cathepsin B in catalyzing the inactivation of the following enzymes: rabbit muscle or liver fructose-1,6-bisphosphate aldolases, rabbit liver fructose-1,6-bisphosphatase and pyruvate kinase, yeast glucose-6-phosphate dehydrogenase, and rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. With glucagon as substrate, both enzymes showed similar peptidyl dipeptidase activities with some minor differences in peptide bond specificity. Cathepsins M and B are similar in size, with apparent molecular weights of 30,200 for cathepsin M and 28,800 for cathepsin B, and in amino acid composition and carbohydrate content. Each contains approximately 2-3 equivalents/mol glucosamine, 3 equivalents/mol mannose, and no fucose or galactosamine. They also show similar microheterogeneity in sodium dodecylsulfate-gel electrophoresis and isoelectric focusing; this microheterogeneity is probably related to differences in glycosylation. Extensive homology in primary structure for the two proteins was indicated by the similar patterns of peptides formed on digestion with trypsin.
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PMID:Purification and properties of rabbit liver cathepsin M and cathepsin B. 406 7

The proline requirement of Salmonella typhimurium strain proB25 can be satisfied by either of the peptides Leu-Pro or Gly-Pro-Ala. A mutant derivative of strain proB25 isolated by penicillin selection in medium containing Leu-Pro as proline source fails to use either Leu-Pro or Gly-Pro-Ala as a source of proline. This strain is a double mutant that lacks two aminoacyl-proline-specific peptidases. One of these enzymes (peptidase Q) catalyzes the rapid hydrolysis of Leu-Pro but does not hydrolyze Gly-Pro-Ala or poly-l-proline. Mutations at a site (pepQ) near metE lead to loss of this activity. The other peptidase (peptidase P) catalyzes the hydrolysis of Gly-Pro-Ala and poly-l-proline but is only weakly active with Leu-Pro as substrate. This enzyme is similar to aminopeptidase P previously described in Escherichia coli (16). Mutations at a locus (pepP) near serA lead to loss of this enzyme.
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PMID:Isolation and characterization of proline peptidase mutants of Salmonella typhimurium. 460 25

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.
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PMID:The isolation of a peptidyl dipeptidase from mouse brain cytosol that cleaves adrenocorticotropic hormone-(7-10) and des-tyrosine-enkephalins. 608 38

Three series of bidentates bearing an hydroxamic or an N-Acyl-N-hydroxy amino group on structures related to Phe-Gly or Phe-Ala exhibit strong inhibitory potency against purified enkephalinase with IC50 values in the 4 to 15 nM range. As with thiol-containing inhibitors, such as thiorphan, the most active compounds are those in which a methylene spacer separates the benzyl P1' moiety from the Zn coordinating residue. Formation of a bidentate complex with the metal enzyme is clearly demonstrated by a loss of potency of three order of magnitude following the removal of one component of the bidentate group. All the compounds studied are unable to interact with angiotensin converting enzyme (IC50 greater than 10,000 nM). Moreover, compounds of the general formula HONHCO-CH2-CH(CH2 phi)-CONH-CH(R)-COOH belonging to the most active series of enkephalinase blockers (IC50 approximately 4 nM) behave also as highly potent and competitive inhibitors (IC50 approximately 10 nM) of a Tyr-Gly releasing dipeptidylaminopeptidase purified from rat brain. The pure steroisomer [(R)-3-(N-hydroxy)carboxamido-2-benzylpropanoyl]-L-alanine designated kelatorphan, exhibits also a relatively good inhibitory potency against aminopeptidases (IC50 approximately 10 microM) and can be considered as the first virtually complete inhibitor of enkephalin metabolism. This very interesting property of inhibiting all three enzymes of enkephalin metabolism could enhance the required selectivity for a possible clinical use of these inhibitors as new analgesic and psychoactive drugs.
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PMID:Bidentate peptides: highly potent new inhibitors of enkephalin degrading enzymes. 608 32

It is known that the serum level of glycylproline aminopeptidase (Gly-Pro-AP) is decreased in the patients with rheumatoid arthritis. In the present study, the serum levels of various hydrolytic enzymes were tested in such patients. In comparison to the controls, many enzymes, including Ala-AP, Ser-AP, Phe-AP, Gly-Pro-AP, Gly-Pro-Leu-AP, dipeptidyl carboxypeptidase (angiotensin converting enzyme), and esterase, showed significantly decreased activities in the patients' sera. Only the activity of Trp-AP was significantly increased. Of these enzymatic activities in serum, several ones including those of Gly-Pro-AP, Ala-AP, Phe-AP, trypsin-like enzyme, and esterase, were significantly correlated with the severity of the disease. Although a part of these findings are compatible with previous observations, they suggest rather more extensive disorders of peptide metabolism in this immunological disease.
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PMID:Decreased serum levels of various hydrolytic enzymes in patients with rheumatoid arthritis. 608 27


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