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:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma prorenin is an inactive form of renin (EC 3.4.99.19) that can be converted to active renin in acid-treated plasma by an endogenous serine protease that is active at alkaline pH (alkaline phase activation). To identify this enzyme we first tested the ability of Hageman factor fragments, plasma kallikrein (EC 3.4.21.8), and plasmin (EC 3.4.21.7) to activate prorenin in acid-treated plasma. All three enzymes initiated prorenin activation; 50% activation was achieved with Hageman factor fragments at 1 microgram/ml, plasma kallikrein at 2-4 microgram/ml, or plasmin at 5-10 microgram/ml. We then showed that the alkaline phase of acid activation occurred normally in plasminogen-free plasma but was almost completely absent in plasmas deficient in either Hageman factor or prekallikrein; alkaline phase activation was restored to these latter plasmas when equal parts were mixed together. Therefore, both Hageman factor and prekallikrein were required for alkaline phase activation to occur. We then found that, although plasma kallikrein could activate prorenin in plasma deficient in either Hageman factor or prekallikrein, Hageman factor fragments were unable to activate prorenin in prekallikrein-deficient plasma. These studies demonstrate that alkaline phase prorenin activation is initiated by Hageman factor-dependent conversion of prekallikrein to kallikrein which, in turn, leads to activation of prorenin. In this fashion, we have revealed a possible link between the coagulation-kinin pathway and the renin-angiotensin system.
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PMID:Initiation of plasma prorenin activation by Hageman factor-dependent conversion of plasma prekallikrein to kallikrein. 4 5

Pretreatment of hog high molecular weight renin for 30 min at 37 degrees C with 0.12 unit of either kallikrein or thrombin significantly increased (p less than 0.001) the amount of angiotensin I formed during subsequent incubations with homologous angiotensinogen. However, the thrombin-treated hog renin had 13 times more activity than the kallikrein-treated enzyme. Aprotinin did not inhibit the kallikrein-mediated activation of renin; the results indicated that aprotinin inhibited renin preferentially. Plasmin (0.25 unit) had little effect on the activity of high molecular weight renin. The molecular weight of hog renin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was not altered after exposure to either kallikrein, thrombin, or plasmin. These results do not exclude the occurrence of a limited proteolytic event or a conformational change beyond the detection of the current method. The data show that the activation of hog high molecular weight renin by thrombin and kallikrein was not associated with the conversion of renin to Mr = 43,000.
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PMID:The effects of kallikrein, plasmin, and thrombin on hog kidney renin. 15 4

Human renin is synthesized as an inactive zymogen (prorenin) which is processed to the active form. We synthesized an 11-amino acid peptide which spans the human prorenin processing site in order to develop a simple assay to study human prorenin activation. Six enzymes which are capable of activating recombinant prorenin in vitro were studied. Four of these enzymes digested the synthetic peptide in a specific fashion, as analyzed by reverse-phase high-performance liquid chromatography. Amino acid analysis of the purified digestion products revealed that trypsin cleaves between Arg-Leu, the authentic processing site, while kallikrein, plasmin and elastase all cleaved at alternate sites. On the other hand, pepsin and cathepsin D did not cleave this substrate, suggesting that the activation of prorenin by these proteases might occur at a site distinct from the authentic processing site. Our data suggest that this synthetic peptide may be used as a simple and specific assay for prorenin activation.
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PMID:Characterization of prorenin activation using a synthetic peptide substrate. 165 85

Plasma inactive renin (IR) can be cold activated (-4 degrees C). This process is called cryoactivation. The mechanism of cryoactivation is not yet elucidated. To investigate the mechanism of cryoactivation, we initially determine the isoelectric point (pI) of plasma active renin (AR) and IR by means of isoelectric focusing. The electrofocusing was performed in a LKB 8100-1 column containing a sucrose gradient and pH 3.5-10 ampholine under 4 degrees C. We found that the pI of AR was 5.0 and 3.9 whereas the pI of IR was 5.6. By using pH 4-6 ampholine, we separated IR from AR and added all fractions containing only IR to each of the electrofocusing column eluates (pH 4-6 ampholine). We found there was no increase in renin activity. If each fraction of electrofocusing eluate (after pH 4-6 ampholine) was cryoactivated, without adding the IR containing fractions, a small increase in angiotensin I (AI) generation was seen in the fractions of pH 4.9-5.1. However, when eluates from the electrofocusing column using pH 3.5-10 ampholine were added to fractions containing only inactive renin, and cryoactivation was subsequently performed, a peak increase in AI generation was found in the fractions corresponding to pH 4.9-5.1. Therefore, cryoactivation may expose certain enzyme(s) which have the pI of 4.9-5.1 and can activate inactive renin. We further found that these fractions could split the synthetic substrate S-2302. Such an activity may be produced by plasmin or related enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A plasma factor participates in the cryoactivation of plasma inactive renin. 168 70

The relation of plasma renin activity (PRA) and plasma levels of angiotensin I (AI) and II (AII) to those of various proteases, including eight endopeptidases and four aminopeptidases, was investigated in 51 normal control subjects. The multivariate study using factor analysis showed that the plasma proteases can be classified into three main components: the aminopeptidase, the plasmin, and the kinin-kallikrein. PRA and AI were related almost exclusively to the aminopeptidase component, while the AII level was related not only to the same component but also to the kallikrein-kinin component. This kind of multivariate study may help in the elucidation of the role of proteases and bioactive peptides, such as angiotensin derivatives, in essential hypertension through a comparison of multivariate relationships in controls and patients.
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PMID:Three main components in plasma proteases and their relation to the renin-angiotensin system. 219 54

The authors determined by radioimmunoassay, spectrophotometry or fibrin plate method the changes of levels of plasma or serum vasomotor (renin, bradykinin, plasmin, lactic acid and ferritin) of guinea-pigs sacrificed by ligature strangulation. This experiment was a part of the studies on the mechanisms of the pulmonary congestion in ligature strangulation. 1) In the ligature strangulation group, significant high levels of plasma renin was observed when compared with the presacrificed group and the beating on occiput group. 2) In both the ligature strangulation group and the beating on occiput group, significant high levels of plasma lactic acid were observed when compared with the presacrificed group. However, between the above-mentioned two groups, there were no significant differences in the levels of this substance. 3) Between the ligature strangulation group and the presacrificed group, there were no significant differences in the levels of plasma bradykinin and plasmin and serum ferritin.
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PMID:[Mechanisms of the pulmonary congestion in ligature strangulation (IV)]. 253 59

Prorenin is an inactive form of the aspartic protease renin. Like pepsinogen, it is activated at low pH. The kinetics of acid activation of prorenin were studied in human amniotic fluid and plasma and in preparations of purified prorenin isolated from amniotic fluid and plasma. Conversion of prorenin (pR) into active renin (R) appeared to be a two-step process involving the generation of an intermediary form of activated prorenin (pRa). The pR----pRa step is an acid-induced reversible change in the conformation of the molecule, and the pRa----R step is proteolytic. pRa----R conversion occurred in amniotic fluid at low pH by the action of an endogenous aspartic protease. In plasma pRa----R conversion occurs after restoration of pH to neutral and is caused by the serine protease plasma kallikrein. pRa----R conversion did not occur in purified preparations of prorenin. Thus, in contrast to pepsinogen, the acid-induced reversible conformational change is not followed by autocatalysis. pRa of amniotic fluid and plasma could be separated from R by affinity chromatography on Cibacron blue F3GA-agarose, and R but not pRa was detected by an immunoassay using monoclonal antibodies reacting with R and not with pR. The first-order rate constant for pR----pRa conversion depends on the protonation of a polar group (or groups) with pK approximately 3.4, the rate constant being proportional to the fraction of pR molecules that have this group protonated. This is analogous to the reversible acid-induced conformational change of pepsinogen that occurs before its proteolytic conversion into pepsin. kcat/Km for pRa----R conversion by plasmin and plasma kallikrein at pH 7.4 and 37 degrees C was 7.8 X 10(6) and 5.2 X 10(6) M-1 min-1, respectively, which was about 50-70 times greater than for pR----R conversion. The susceptibility of pRa to proteolytic attack is high enough for the intrinsic factor XII-kallikrein pathway to cause rapid pRa----R conversion at 37 degrees C even in whole blood with its abundance of serine protease inhibitors. Formation of pRa may occur in vivo in an acidic cellular compartment, such as exo- or endocytotic vesicles.
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PMID:Two-step prorenin-renin conversion. Isolation of an intermediary form of activated prorenin. 354 90

A highly active angiotensin-producing enzyme (enzyme II) was obtained from dog serum by acid treatment and fractionation to remove angiotensinase and converting enzyme, separate an inhibitor, and convert an inactive precursor (proenzyme II) to enzyme II. Proenzyme II was found to be converted to enzyme II by an endogenous activating enzyme identified as plasmin. Conversion was also caused by the interaction of bacterial streptokinase with human proactivator, by trypsin, and by an activator formed from liver tissue extract and dog serum. Neither plasma kallikrein nor the labile, human extrinsic tissue-type plasminogen activator induced activation. The inhibitor, which normally blocks the activation of proenzyme II, was unusually stable against high temperatures and extremes of pH, and it was not identical to any of the six known protease inhibitors of serum. Enzyme II was not identical to other angiotensin-producing enzymes such as enzyme I, renin, cathepsin D, pepsin, plasmin, tonin, or cathepsin G. Enzyme II reacted maximally at pH 4.7 and produced up to 2250 ng of angiotensin I/ml serum/hr from the substrate of dog serum (i.e., amounts 3200-fold higher than that produced by endogenous renin of normal dog serum). Since at pH 7.2, angiotensin I formation is still about 30 times higher than that of renin, enzyme II may be physiologically active under some conditions.
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PMID:Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation. 390 15

Immunization with renin from the kidneys of hog, beef, dog, rabbit and man induced the formation of a highly active enzyme (enzyme I) in the serum of dogs, guinea pigs, rabbits and rats. Enzyme I produces angiotensin I maximally at pH 4.7, up to 2900 ng/ml serum/h, i.e. at a rate 2500 times higher than the endogenous renin of normal serum. At pH 7.2 the angiotensin I production by enzyme I is about 16 to 28 times higher than that of plasma renin. Enzyme I is produced by immunization with renin and not by other kidney proteins. Enzymatically-active renin is required and separate mechanisms are involved in the formation of enzyme I and antirenin. Enzyme I is not identical to renin, pepsin, cathepsin D, plasmin, tonin or cathepsin G and it is inhibited by pepstatin, but not by diisopropyl fluorophosphate.
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PMID:Angiotensin-producing enzyme I of serum: formation by immunization with renin. 609 39

A new affinity chromatographic procedure was devised to purify inactive renin by using a selective hydrophobic interaction of inactive renin to octyl-Sepharose. Additional extensive purification was accomplished by immunoaffinity chromatography on antihuman renin immunoglobulin G-Sepharose. A trace amount of active renin was removed by chromatography on pepstatin-Sepharose. Human plasma inactive renin purified by this method was free from protease inhibitors and permitted the investigation of protease-mediated activation without the acid treatment which was used previously to remove inhibitors. Human plasma kallikrein, human plasmin, cathepsin B1, and arginine esteropeptidases associated with mouse epidermis growth factor and nerve growth factor were effective activators. Human urinary kallikrein, hog pancreatic kallikrein, and rat urinary esterase A were inefficient activators of low potency. Thrombin, factor Xa, factor XIIa, and urokinase did not activate inactive renin. The in vitro activation of 56,000-dalton inactive renin by these proteases was not accompanied by a recognizable reduction in molecular weight. Activation required plasma albumin, presumably as a protecting substance. These results suggest that human inactive renin can be activated by a minimum change in its molecular size.
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PMID:Human plasma inactive renin: purification and activation by proteases. 621 31


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