Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein (a) [Lp(a)] is a plasma component whose concentration is related to the development of atherosclerosis, although the underlying mechanisms are not known. Lp(a) contains a unique structure, apolipoprotein (a), that shares partial homology with plasminogen. We now report that plasmin catalyzes the binding of Lp(a) to both immobilized fibrinogen and fibrin in a manner analogous to our previously reported studies with plasminogen. Plasmin treatment of immobilized fibrinogen induces a 3.7-fold increase in Lp(a) binding. Low density lipoprotein, molecules similar to Lp(a) but lacking apolipoprotein (a), bind poorly to immobilized fibrinogen and binding is not increased by plasmin. Trypsin but not neutrophil elastase also increases the binding of Lp(a) to fibrinogen. Lp(a) also complexes to plasmin-fibrinogen digests, and binding increases in proportion to the time of plasmin-induced fibrinogen degradation. Lp(a) binding is lysine-binding site dependent as it is inhibited by epsilon-aminocaproic acid. Lp(a) inhibits the binding of plasminogen to plasmin-modified immobilized fibrinogen, indicating that both molecules compete for similar lysine-binding sites. These findings demonstrate an affinity between Lp(a) and protease-modified fibrinogen or fibrin and thereby provide a potential mechanism to explain the association between thrombosis, coronary atherosclerosis, and increased blood concentrations of Lp(a).
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PMID:Plasmin catalyzes binding of lipoprotein (a) to immobilized fibrinogen and fibrin. 252 34

We have previously shown that a functional free apolipoprotein[a] (apo[a]) can be isolated from its parent lipoprotein[a] (Lp[a]) by a mild reductive procedure. To shed further light on the properties of Lp[a] and apo[a] we subjected them to a limited proteolysis by porcine pancreatic elastase. This enzyme cleaved both at the Ile3520-Leu3521 bond in the linker between kringles IV-4 and IV-5 of apo[a] generating two fragments F1 and F2. In contrast to F1, which represented the N-terminal portion of apo[a] and was functionally inert, F2, representing the C-terminal domain, bound to lysine-Sepharose, fibrinogen, and fibronectin and formed a miniLp[a] particle when incubated with LDL. The proteolytic pattern by pancreatic elastase was also exhibited by human leukocyte elastase. F1, injected intravenously into normal mice, was rapidly cleared (Ty2, 2.9 h) and after 1 h fragments in the size range of 100-33 kDa were observed in the urine. In turn, F2 had a longer residence time (Ty2, 5 h) and was excreted in the urine only after 5 h as fragments of 70-45 kDa. Fragments in the same size range as found after F1 injection were also present in the urine after injection of apo[a] or Lp[a]. Moreover, apo[a] fragments of the size seen in mouse urine were spontaneously present in normal human urine and appeared derived from larger apo[a] fragments in the plasma. Our results indicate that enzymes of the elastase family cleave human apo[a] in vitro into two main fragments that differ in structural and functional properties and metabolic behavior. The comparable size of apo[a] fragments observed in the urine of humans and injected mice invites the speculation that enzymes of the elastase family may play a role in the biology of Lp[a] in vivo.
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PMID:Functional and metabolic differences between elastase-generated fragments of human lipoprotein[a] and apolipoprotein[a]. 886 63

Lipoprotein [a] (Lp[a]) contains equimolar amounts of apoB-100 and apolipoprotein [a] (apo[a]). Both proteins are amenable to degradation in vivo by mechanisms yet to be clearly defined. In this study, we examined the in vitro susceptibility of LDL and Lp[a], obtained from the same donor, to oxidation by either Cu(2)+ or the combined Crotalus adamanteus phospholipase A2 and soybean lipoxygenase system, monitoring the course of the reaction by the generation of conjugated dienes and fatty acids. In some experiments, treatment with leukocyte elastase (LE) or matrix metalloproteinase 12 (MMP-12) was administered before and after the oxidative step. In the case of Lp[a] we found that with both oxidizing systems, conditions that caused the breakdown of apoB-100 did not degrade apo[a] although oxidation-mediated changes were detected in the latter by intrinsic tryptophan fluorescence spectroscopy. Similar results were obtained with a reassembled Lp[a] obtained by incubating free apo[a] with LDL. Both apo[a] and apoB-100 were cleaved by LE and MMP-12 but the enzymatic cleavage was more marked when the preoxidized proteins were used as a substrate. Taken together, our in vitro studies indicate that apo[a] but not apoB-100 resists oxidative fragmentation, whereas both proteins are cleaved by enzymes of the serine and metalloproteinase families. We speculate that the fragments of apo[a] observed in vivo may be preferentially generated by proteolytic rather than oxidative events, whereas apoB-100 can be degraded by both mechanisms.
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PMID:Oxidative events cause degradation of apoB-100 but not of apo[a] and facilitate enzymatic cleavage of both proteins. 1159 Feb 23