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

Catalytic amounts of bovine beta-trypsin, bovine alpha-chymotrypsin and porcine plasmin establish a true thermodynamic equilibrium between virgin (I) (reactive site Lys15-Ala16 peptide bond intact) and modified (I) (this bond hydrolyzed) bovine trypsin/kallikrein inhibitor (Kunitz). The very slow reaction rates for attaining equilibrium are pH-dependent and differ for different enzymes. Optimal rates are for beta-trypsin at pH 3.75, for alpha-chymotrypsin at pH 5.5, and for plasmin at pH 5.0. Under conditions of optimum pH the equilibrium is reached with the highest rate by plasmin. In 10(-5)M inhibitor solutions the equilibrium concentrations of virgin and modified inhibitor are established by plasmin after almost 300 days starting from either pure virgin or pure modified inhibitor. Thus, the hydrolysis constant KHyd = [I]/[I] is determined to be 0.33 at pH 5.0. In spite of many unsuccessful attempts, this demonstrates that the reactive site peptide bond Lys15-Ala16 in the bovine trypsin inhibitor (Kunitz) can be hydrolyzed by catalytic amounts of endopeptidase. It further confirms that the hydrolyzed Lys15-Ala16 peptide bond in modified inhibitor is subject to thermodynamic control resynthesis.
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PMID:Hydrolysis-resynthesis equilibrium of the lysine-15--alanine-16 peptide bond in bovine trypsin inhibitor (Kunitz). 0 70

Three highly specific trypsin-like proteases from mouse submaxillary gland; nerve growth factor gamma subunit, beta nerve growth factor-endopeptidase, and epidermal growth factor-binding protein were tested for kallikrein activity. Low molecular weight kininogen was purified from mouse plasma and used as substrate for the three enzymes, and the kinin released by the enzymes was assayed by its ability to induce contraction of isolated rat uterus. All three enzymes were found to have significant kininogenase activity, and the most active enzyme, beta nerve growth factor-endopeptidase, has activity comparable to authentic kallikreins from other glandular sources. Essentially all of the kininogenase activity of submaxillary gland co-purifies with beta nerve growth factor-endopeptidase. Hence, beta nerve growth factor-endopeptidase appears to be identical with submaxillary gland kallikrein. Nerve growth factor gamma subunit, epidermal growth factor-binding protein, and beta nerve growth factor-endopeptidase have similar amino acid compositions and molecular weights, and are immunologically similar. Comparison of published partial primary sequence data confirms our conclusion that nerve growth factor gamma subunit, epidermal growth factor-binding protein, and kallikrein are very closely related enzymes. It is postulated that these three enzymes are members of a larger family of similar enzymes, all of which are involved in the processing of precursors to polypeptide hormones and growth factors.
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PMID:The relationship between glandular kallikrein and growth factor-processing proteases of mouse submaxillary gland. 11 Aug 5

To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a monospecific antibody against the antigenically identical urinary kallikrein (urokallikrein). The localization of glandular pancreatic kallikrein to the beta cells of the islets was the same as that of insulin in normal human pancreas and in two islet-cell tumors. When beta cells were lacking in islet-cell tumors or in the pancreas of a patient with juvenile-onset diabetes, kallikrein antigen was not detectable. Anti-urokallikrein absorbed with purified urinary or pancreatic kallikrein no longer identified a pancreatic antigen, whereas absorption with insulin had no effect. The beta-cell localization of human pancreatic kallikrein, an endopeptidase that, in concert with carboxypeptidase B, converts bovine proinsulin to a polypeptide with the electrophoretic mobility of insulin, suggests that pancreatic kallikrein may be involved in the physiologic activation of proinsulin.
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PMID:Identification of human glandular kallikrein in the beta cell of the pancreas. 22 May 34

A pancreatic endopeptidase localized to the beta-cells of the pancreas by immunohistochemical techniques has been purified to homogeneity by following its functional and antigenic characteristics as a glandular kallikrein (EC 3.4.21.8). The enzyme gave a single stained band on alkaline disc gel electrophoresis which corresponded in location with the kinin-generating activity eluted from a replicate gel, was of 54,000 molecular weight by gel filtration, was devoid of caseinolytic activity, elicited a monospecific antiserum in a rabbit, and gave a line of complete identity with a single constituent in pancreatic extract, crude urine, and purified urokallikrein when analyzed with monospecific antibody to urokallikrein. The pancreatic glandular kallikrein generated three cleavage products of increasing anodal mobility from bovine and porcine proinsulin, and the presence of pancreatic kininase or bovine carboxypeptidase B increased the quantity of these products. Although the conversion products did not correspond to diarginyl- and monoarginylinsulin, the product of intermediate mobility was also obtained when proinsulin was treated with a low concentration of trypsin in the presence of kininase. The most rapidly migrating product did correspond to desalanylinsulin in the reference standard. Kininase alone had no action on proinsulin, and aprotinin prevented cleavage by kallikrein alone or in combination with kininase. Although the chemical structure of the proinsulin cleavage products has not been established, human pancreatic kallikrein is considered a putative activator of proinsulin because of its location in the beta-cell, its preferential action on proinsulin and kininogen as compared to azocasein, and its capacity to generate insulin intermediate products that are further modified by human pancreatic kininase or bovine carboxypeptidase B.
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PMID:Sequential cleavage of proinsulin by human pancreatic kallikrein and a human pancreatic kininase. 38 42

All four components of the kallikrein-kinin system--kininogens, tissue kallikreins, kinins, and kininases--have been found in human male genital secretions. Kinins are continuously released from seminal plasma kininogens through limited proteolysis by kininogenases like tissue kallikrein from prostate and sperm acrosin. Kinins are the terminal effectors of the kallikrein-kinin system and increase sperm motility and sperm metabolism at nanomolar concentrations. Recent investigations indicate that these effects are possibly mediated by a specific sperm membrane integrated bradykinin receptor, subtype B2. The two major kininase that are present in seminal plasma are kininase II and neutral metallo-endopeptidase. Kininase II, which is identical with angiotensin-converting enzyme, is also involved in the renin-angiotensin system as it converts angiotensin I into angiotensin II and thus is the connecting enzyme of both systems. Apart from the observed effects of kinins on sperm motility, the kallikrein-kinin system is thought to be involved in the regulation of spermatogenic functions of the testis: in the rat, kallikrein activates Sertoli cell function, increases the relative number of spermatocytes and the [3H] thymidine incorporation of testicular tissue, enhances glucose-intake, and increases testicular blood flow. Clinical trials showed that systemic administration of kallikrein may be particularly useful for treatment of infertile men suffering from asthenozoospermia and/or oligozoospermia. During kallikrein therapy, the number of spermatozoa and both quantitative and qualitative sperm motility increased, and a significant improvement of the conception rate was achieved. An increased sperm number was also observed after application of the specific kininase II inhibitor captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible effects of the kallikrein-kinin system on male reproductive functions. 131 46

We contrasted the effects of D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg-TFA (kinin receptor antagonist), of aprotinin (kallikrein inhibitor), and of combined treatment with captopril (kininase II inhibitor) and phosphoramidon (neutral endopeptidase 24.11 inhibitor) on renal function of rats with and without 14-day deoxycorticosterone pretreatment (DOC, 25 mg.kg-1.wk-1 sc). Neither the kinin antagonist nor aprotinin affected renal function in rats with and without DOC pretreatment. Combined treatment with captopril and phosphoramidon caused in rats with and without DOC pretreatment augmentation (P less than 0.05) of kinin excretion (50-64%), glomerular filtration rate (12-11%), and sodium excretion (46-48%). In DOC-pretreated rats undergoing infusion of captopril and phosphoramidon, the superimposed administration of either the kinin antagonist or aprotinin caused the lowering of renal plasma flow, glomerular filtration rate, and sodium excretion. These effects of the kinin antagonist and aprotinin in rats infused with kininase inhibitors may be the consequence of blockade, respectively, of the renal actions and synthesis of kinins that, when in excess, elicit renal vasodilation and increase glomerular filtration rate and sodium excretion. Collectively, these observations suggest regulatory influence of kinins during conditions featuring increased renal kinin levels.
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PMID:Effects of a kinin antagonist on renal function in rats. 169 May 17

The metabolism of atrial natriuretic peptide (ANP) and Cys-105-Phe-106-cleaved ANP (ANP) was studied during constant infusion of 125I-labelled peptides in rats. Analysis of circulating radioactivity indicated rapid clearance of ANP and ANP', with mean half-lives of 0.42 and 1.04 min respectively. H.p.l.c. fractionation of plasma taken during the infusion of labelled ANP revealed the presence of three radioactive fragments, the major one co-eluting with 125I-ANP'. These fragments correspond to cleavage products previously found to be generated in vitro by the action of endopeptidase 24.11 (E-24.11). On evaluating the effects of peptidase inhibitors, a significant increase in the half-life of ANP was observed with phosphoramidon (t1/2 7.8 min) and aprotinin (t1/2 5.4 min). A maximal inhibition of ANP degradation was obtained when both inhibitors were given simultaneously (t1/2 15 min). In blood samples taken during infusion of 125I-ANP and phosphoramidon, the intact peptide accounted for more than 90% of total circulating radioactivity, and no cleavage product was present in detectable amounts. Phosphoramidon had no effect on the metabolism of infused ANP'. In contrast, when 125I-ANP' was infused together with aprotinin, the rate of degradation of the infused peptide was reduced by more than 80%. It is proposed that two different peptidase activities, E-24.11 and a kallikrein-like proteinase, are responsible for the cleavage of ANP in the circulation. The Cys-Phe-cleaved ANP would in turn be degraded by kallikrein and not by E-24.11.
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PMID:Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat. 169 65

Atrial natriuretic peptide (ANP) is a 28-amino-acid hormone involved in the regulation of fluid balance. In circulation, the proteolytic inactivation of ANP has been demonstrated to involve both membrane metalloendopeptidase and an aprotonin-sensitive activity, probably corresponding to kallikrein [Vanneste, Y., Pauwels, S., Lambotte, L., Michel, A., Dimaline, R. & Deschodt-Lanckman, M. (1990) Biochem. J. 269, 801-806]. In the present study, we focused on the aprotinin-sensitive pathway of ANP metabolism. In order to identify the cleavage sites recognized by kallikrein within the sequence of the hormone, tissue kallikrein was purified to homogeneity from human urine and the degradation of human ANP by the enzyme preparation was studied. Our results demonstrate that both intact and Cys7-Phe8-cleaved ANP, the initial metabolite produced in circulation by the metallo-endopeptidase, are substrates in vitro for purified tissue kallikrein. However, the Cys-Phe-cleaved peptide was degraded approximately fourfold faster than the intact hormone by the purified enzyme. The first degradation step of ANP by tissue kallikrein involves two cleavages occurring at the bonds Arg3-Arg4 and Gly16-Ala17, generating an inactive, open-ring metabolite. Incubation of ANP for a longer period with the enzyme led to the generation of several additional degradation fragments. Ten peaks were separated by HPLC and characterized by amino acid analysis. The results allowed the identification of a total of eight peptide bonds susceptible to hydrolysis by tissue kallikrein in the sequence of ANP: Arg3-Arg4, Ser5-Ser6, Cys7-Phe8, Arg11-Met12, Gly16-Ala17, Gly20-Leu21, Ser25-Phe26 and Arg27-Tyr28. These results indicate that the aprotinin-sensitive activity involved in the metabolism of ANP in circulation could correspond to tissue kallikrein. However, clear identification of ANP as a novel physiological substrate of the enzyme will need further investigation.
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PMID:Hydrolysis of intact and Cys-Phe-cleaved human atrial natriuretic peptide in vitro by human tissue kallikrein. 182 98

A tissue-kallikrein-related proteinase present in rat submaxillary glands, which was previously called endopeptidase k, has been further characterized and compared with other members of the kallikrein family. The partial primary structure of this proteinase, now called kallikrein k10, is very similar to that of proteinase B [Kato, H., Nakanishi, E., Enjyoji, K., Hayashi, I., Oh-Ishi, S. & Iwanaga, S. (1987) J. Biochem. (Tokyo) 102, 1389-1404] and T-kininogenase [Xiong, W., Chen. L. M. & Chao, J. (1990) J. Biol. Chem. 265, 2822-2827], but no corresponding gene or mRNA has so far been found. Kallikrein k10 is microheterogeneous due to variable glycosylation of its N-terminal light chain and to variable processing at its kallikrein loop, as shown by endo-beta-N-acetylglucosaminidase F treatment, amino acid sequence analysis and mass spectrometry. The enzymatic properties of the two molecular varieties of kallikrein k10 towards synthetic fluorogenic substrates are not significantly different. Both cleave specifically after Arg residues, but, in contrast to true tissue kallikrein, may accommodate either polar or nonpolar residues at position P2. Kallikrein k10 also differs from tissue kallikrein by its sensitivity to soyabean trypsin inhibitor. Its biological function may therefore differ from that of tissue kallikrein, especially as it does not induce a transient decrease in blood pressure when injected in vivo.
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PMID:Microheterogeneity of rat submaxillary gland kallikrein k10, a member of the kallikrein family. 202 64

The physiological role of renal kallikrein-kinin system in human is discussed by the three following topics. Localization of each component of renal kallikrein-kinin system: Kallikrein is localized in the apical site of the distal tubular epithelial cells and collecting ducts by the immunostaining method. Following the stop-flow method in dog kidney, kallikrein and kinin are recognized in the distal tubules. Kininase I, II and neutral endopeptidase (enkephalinase) are localized not only in the proximal tubules, but also in the distal tubules. The localization of kininases is further confirmed by the stop-flow method pretreated with specific inhibitors for each of the kininases. Sodium metabolism and renal kallikrein-kinin system: In normal subjects, fractional excretions of sodium and inorganic phosphorus which reflect the total and proximal sodium reabsorption, show significantly positive correlations for both urinary kallikrein and kinin excretions. In the case of 0.9% saline infusion, the activity of renal kallikrein-kinin system is augmented following the infusion as shown in the increases of urinary kallikrein and kinin excretions and the decreases of urinary kininases excretions. Relation to other renal depressor systems: The close relations among renal dopamine, kallikrein-kinin and prostaglandin systems have been suggested by a dopamine infusion study. Dopamine may augment the activity of the renal kallikrein-kinin system through both the increases of renal prekallikrein synthesis and kallikrein specific activity. From these studies reported up to the present, it is suggested that the renal kallikrein-kinin system produced in the distal nephron in the kidney may play a role in the sodium metabolism with other renal depressor systems in addition to its own action.
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PMID:Physiological role of renal kallikrein-kinin system in human. 255 57


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