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==Regulación da actividade das serina proteases==
Os organismos hóspedes deben asegurarse que a actividade das serina proteases está ben regulada. Isto conséguese ao ser necesaria unha activación inicial da protease, e pola secreción de [[inhibidor encimático|inhibidores]].
Host organisms must ensure that the activity of serine proteases is adequately regulated. This is achieved by a requirement for initial protease activation, and the secretion of inhibitors.
===Activación de cimóxenos===
Os [[cimóxeno]]s (ou zimóxenos) son os precursores de maior tamaño xeralmente inactivos dun encima. Se os encimas dixestivos fosen activos desde o momentos en que se sintetizan, empezarían inmediatamente a dixerir os órganos e tecidos que os sintetizaron. A [[pancreatite aguda]] é un exemplo de doenza na cal hai unha activación prematura dos encimas dixestivos no páncreas, e como resultado prodúcese autodixestión (autólise). Isto tamén complica as investigacións postmortem, xa que o páncreas a miúido se autodixire antes de que poida ser avaliado visualmente.
[[Zymogen]]s are the usually inactive precursors of an enzyme. If the digestive enzymes were active when synthesized, they would immediately start chewing up the synthesizing organs and tissues. [[Acute pancreatitis]] is such a condition, in which there is premature activation of the digestive enzymes in the pancreas, resulting in self-digestion (autolysis). It also complicates [[postmortem investigation]]s, as the pancreas often digests itself before it can be assessed visually.
Os cimóxenos son grandes estruturas proteicas inactivas, que teñen a capacidade de perder unha parte por clivaxe ou cambiar formando un encima máis pequeno activado. Só despois da activación o sitio activo ten a conformación axeitada para que teña lugar a [[proteólise]].
Zymogens are large, inactive structures, which have the ability to break apart or change into the smaller activated enzymes. The difference between zymogens and the activated enzymes lies in the fact that the active site for catalysis of the zymogens is distorted. As a result, the substrate polypeptide cannot bind effectively, and [[proteolysis]] does not occur. Only after activation, during which the conformation and structure of the zymogen change and the active site is opened, can [[proteolysis]] occur.
{| class="wikitable"
| '''ZymogenCimóxeno''' || '''EnzymeEncima''' || '''NotesNotas'''
|-
| ''Tripsinóxeno'' || [[tripsina]] || Cando o tripsinóxeno entra no [[intestino delgado]] procedente do páncreas, unha [[enteropeptidase]] segregada pola mucosa [[duodeno|duodenal]] cliva o enlace peptídico entre a lisina 15 e a isoleucina 16 do cimóxeno. Como resultado, o cimóxeno tripsinóxeno rompe dando lugar a tripsina. Como a propia tripsina pode tamén romper enlaces peptídicos nos que intervén a lisina, unha vez que se formou unha pequena cantidade inicial de tripsina, ela mesma pode participar na clivaxe do seu propio cimóxeno e xerar máis tripsina. O proceso da activación da tripsina pode, xa que logo, considerarse [[autocatalítico]].
| ''Trypsinogen'' || [[trypsin]] || When trypsinogen enters the [[small intestine]] from the pancreas, [[enteropeptidase]] secretions from the duodenal mucosa cleave the lysine 15 - isoleucine 16 peptide bond of the zymogen. As a result, the zymogen trypsinogen breaks down into trypsin. Recall that trypsin is also responsible for cleaving [[lysine]] peptide bonds, and thus, once a small amount of trypsin is generated, it participates in cleavage of its own zymogen, generating even more trypsin. The process of trypsin activation can thus be called [[autocatalytic]].
|-
| ''Quimotripsionóxeno'' || [[quimotripsina]] || Unha vez que a tripsina rompe o enlace peptídico entre a [[arxinina]] 15 e a isoleucina 16 do cimóxeno quimotripsinóxeno, a nova estrutura xerada chamada ''pi-quimotripsina'' sofre [[autólise]], xerando quimotripsina activa.
| ''Chymotrypsinogen'' || [[chymotrypsin]] || After the Arg 15 - Ile 16 bond in the chymotrypsinogen zymogen is cleaved by trypsin, the newly generated structure called a ''pi-chymotrypsin'' undergoes [[autolysis]] (self digestion), yielding active chymotrypsin.
|-
| ''Proelastase'' || [[elastase]] || ItÉ isactivada activatedao byser cleavageclivada throughpola trypsintripsina.
|}
Como pode verse, a activación do tripsinóxeno a tripsina é esencial, porque activa a súa propia reacción, e tamén a reacción da quimotripsina e a elastase. Por tanto, é esencial que esta activación non ocorra prematuramente. Hai varias medidas de protección no organismo para previr a autodixestión, como son:
As can be seen, trypsinogen activation to ''trypsin'' is essential, because it activates its own reaction, as well as the reaction of both ''chymotrypsin'' and ''elastase''. Therefore, it is essential that this activation does not occur prematurely. There are several protective measures taken by the organism to prevent self-digestion:
*A activación do tripsinóxeno pola tripsina é relativamente lenta.
*The activation of trypsinogen by trypsin is relatively slow
*Os cimóxenos son almacenados en [[gránulo (bioloxía)|gránulos]] de cimóxeno, que son vesículas con paredes que se cre son resistentes á proteólise.
*The zymogens are stored in zymogen granules, capsules that have walls that are thought to be resistant to proteolysis.
===Inhibición===
Hai algúns [[inhibidor encimático|inhibidor]]es que lembran o intermediario tetraédrico, e pode ocupar o sitio activo do encima, impedindo que este poida funcionar axeitadamente.
There are certain [[Enzyme inhibitor|inhibitor]]s that resemble the tetrahedral intermediate, and thus fill up the active site, preventing the enzyme from working properly. Trypsin, a powerful digestive enzyme, is generated in the pancreas. Inhibitors prevent self-digestion of the pancreas itself.
As serina proteases son inhibidas por diversos inhibidores, entre os que están inhibidores químicos sintéticos para a investigación ou propósitos terapéuticos, e inhibidores proteicos naturais. Unha familia de inhibidores naturais é a das chamadas "[[serpina]]s" (abreviación de [[inhibidor das serina proteases|inhibidores das serina proteases]]), que poden formar un enlace [[covalente]] coas serina proteases, inhibindo a súa función. As ''serpinas'' mellor estudadas son a [[antitrombina] e a [[alfa 1-antitripsina]], estudadas polo seu papel na [[coagulación]]/[[trombose]] e [[emfisema]]/[[A1AT]], respectivamente.
Serine proteases are paired with serine protease [[Enzyme inhibitor|inhibitors]], which turn off their activity when they are no longer needed.<ref>[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Serine_Proteases.html#Serpins Kimball's Biology Pages, Serine Proteases]{{Self-published inline|date=May 2011}}</ref>
Moléculas pequenas artificiais que son inhibidores irreversibles son [[AEBSF]] e [[PMSF]].
AIdentificouse familyunha offamilia [[arthropod]]de serineinhibidores peptidasede inhibitors,serina calledproteases de [[ pacifastinartrópodo]] s, has been identified inchamadas [[ locustpacifastina]]s , anden [[crayfish]]isectos e crustáceos, andque maypoden functionfuncionar inno thesistema arthropodinmunitario [[Immune_system|immunedeses system]]animais.<ref name="pmid18775459">{{cite journal| author=Breugelmans B, Simonet G, van Hoef V, Van Soest S, Vanden Broeck J| title=Pacifastin-related peptides: structural and functional characteristics of a family of serine peptidase inhibitors. | journal=Peptides | year= 2009 | volume= 30 | issue= 3 | pages= 622-32 | pmid=18775459 | doi=10.1016/j.peptides.2008.07.026 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18775459 }} </ref> ▼Serine proteases are inhibited by a diverse group of [[Enzyme inhibitor|inhibitors]], including synthetic chemical inhibitors for research or therapeutic purposes, and also natural proteinaceous inhibitors. One family of natural inhibitors called "serpins" (abbreviated from [[serine protease inhibitor]]s) can form a [[covalent]] bond with the serine protease, inhibiting its function. The best-studied ''serpins'' are [[antithrombin]] and [[alpha 1-antitrypsin]], studied for their role in [[coagulation]]/[[thrombosis]] and [[emphysema]]/[[A1AT]], respectively.
Artificial irreversible small molecule inhibitors include [[AEBSF]] and [[PMSF]].
▲A family of [[arthropod]] serine peptidase inhibitors, called [[pacifastin]], has been identified in [[locust]]s and [[crayfish]], and may function in the arthropod [[Immune_system|immune system]].<ref name="pmid18775459">{{cite journal| author=Breugelmans B, Simonet G, van Hoef V, Van Soest S, Vanden Broeck J| title=Pacifastin-related peptides: structural and functional characteristics of a family of serine peptidase inhibitors. | journal=Peptides | year= 2009 | volume= 30 | issue= 3 | pages= 622-32 | pmid=18775459 | doi=10.1016/j.peptides.2008.07.026 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18775459 }} </ref>
==Papel en enfermidades==
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