Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.27 (thermolysin)
 1,894 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although about 90% of human renin circulates as inactive prorenin, the mechanism of prorenin activation in vivo is not known. We found that human polymorphonuclear leukocytes (PMN) activate prorenin at a neutral pH. Prorenin was partially purified from human amniotic fluid, and its activation was measured by the release of angiotensin I from sheep angiotensinogen. In control experiments, thermolysin was the standard activator. PMN cells were separated from blood and, after N2 cavitation or degranulation by cytochalasin, were fractionated by differential centrifugation. Elastase and cathepsin G activities were determined with synthetic fluorescent substrates. The activators of prorenin concentrated in the azurophil granules were released by Triton; most of the activation was due to elastase. Elastase, purified from human PMN, activated prorenin completely. The activation by the granular fraction was inhibited 77% by a specific elastase inhibitor in the presence of a detergent, but only 22% by a cathepsin G inhibitor. After inhibition of elastase, the residual activity was inhibited by diisopropylfluorophosphate; thus, it was due to a serine protease(s) such as cathepsin G. We suggest that human renin fully activated by elastase may still contain an N-terminal pentapeptide fragment of the propeptide.
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PMID:Activation of human prorenin by neutrophil elastase. 331 66

Human renin occurs in a latent form as prorenin in blood and amniotic fluid. We found that the metalloprotease thermolysin is a more potent activator of amniotic and plasma prorenin than trypsin, provided the thermolysin alpha 2-macroglobulin plasma inhibitor was inactivated. Thermolysin fully activated amniotic prorenin at a 23-fold lower molar concentration than trypsin, and renin activated by thermolysin was more stable than when activated by trypsin. Thermolysin also activated plasma prorenin at a 16-fold lower concentration than trypsin in the presence of methylamine (100 mM). Thermolysin activated prorenin directly, because added inhibitors of other endogenous proteases did not block the activation. The maximum activation values obtained after incubation with trypsin or thermolysin in plasma samples from 17 normotensive and 58 hypertensive subjects were similar. The mean renin concentration did not differ significantly in normotensives and hypertensives, but after activation, total renin was significantly higher in hypertensive subjects (89.8 vs. 53.4 ng angiotensin I/h . ml). The Km of the substrate, angiotensinogen, was about the same with both active renin and activated prorenin (281-290 nM). The mol wt of prorenin was 60,000 after gel filtration; activation by thermolysin reduced it to 51,000. Thus, thermolysin, which has a different peptide bond specificity than trypsin, is another model for a prorenin activator.
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PMID:Activation of plasma and amniotic prorenin by metalloprotease and trypsin. 351 Oct 83