Desfosforilación: Diferenzas entre revisións

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== Papel da desfosforilación en doenzas ==
=== Patoloxía ===
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Excessive dephosphorylation of the membrane ATPases and proton pumps in the gastrointestinal tract leads to higher secretory rates of caustic peptic acids. These result in heartburn and esophagitis. In combination with ''[[Helicobacter pylori]]'' infection, peptic ulcer disease is caused by the elevated pH dephosphorylation elicits.<ref name="Robinson 709-15">{{cite journal|last=Robinson|first=M|title=Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases.|journal=International journal of clinical practice|date=Jun 2005|volume=59|issue=6|pages=709–15|pmid=15924600|doi=10.1111/j.1368-5031.2005.00517.x}}</ref>
 
ExcessiveUnha dephosphorylationdesfosforilación ofexcesiva the membranedas ATPases andde protonmembrana pumpse indas thebombas gastrointestinalde tractprotóns leadsdo totracto highergastrointestinal secretoryorixina ratesunha ofsecreción causticelevada pepticdos acidsácidos pépticos cáusticos. TheseIsto resultorixina inardores heartburnde andestómago esophagitise esofaxite. InAs combinationúlceras withpépticas ''[[Helicobacterorixínanse pylori]]''polo infection,pH pepticextremo ulcerque diseaseorixina isa causeddesfosforilación byen thecombinación elevatedcunha pHinfección dephosphorylationpor elicits''[[Helicobacter pylori]]''.<ref name="Robinson 709-15">{{cite journal|last=Robinson|first=M|title=Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases.|journal=International journal of clinical practice|date=Jun 2005|volume=59|issue=6|pages=709–15|pmid=15924600|doi=10.1111/j.1368-5031.2005.00517.x}}</ref>
The microtubule-associated protein [[tau]] is abnormally hyperphosphorylated when isolated from the brain of patients who suffer from [[Alzheimer's disease]]. This is due to the dysfunction of dephosphorylation mechanisms at specific amino acids on the tau protein. Tau dephosphorylation is catalysed by protein phosphatase-2A and phosphatase-2B. Deficiency or modification of one or both proteins may be involved in abnormal phosphorylation of tau in Alzheimer's disease<ref name="pmid7838376">{{cite journal |author=Gong CX, Grundke-Iqbal I, Iqbal K |title=Dephosphorylation of Alzheimer's disease abnormally phosphorylated tau by protein phosphatase-2A |journal=Neuroscience |volume=61 |issue=4 |pages=765–72 |date=August 1994 |pmid=7838376 |doi= 10.1016/0306-4522(94)90400-6|url=}}</ref>
 
TheA microtubule-associatedproteína proteinasociada a microtúbulos [[proteína tau|tau]] isestá abnormallyanormalmente hyperphosphorylatedhiperfosforilada whencando isolatedse fromilla thedo braincerebro ofde patientspacientes who suffer fromda [[Alzheimer'senfermidade diseasede Alzheimer]]. ThisIsto isdébese dueá todisfunción thedos dysfunctionmecanismos ofda dephosphorylationdesfosforilación mechanismsen ataminoácidos specificespecíficos aminoda acids on theproteína tau protein. TauA dephosphorylationdesfosforilación isde catalysedtau está catalizada bypola proteinproteína phosphatasefosfatase-2A ande phosphatasefosfatase-2B. DeficiencyA ordeficiencia modificationou ofmodificación onedunha orou bothvarias proteinsproteínas maypode beestar involvedimplicada inna abnormalfosforilación phosphorylationanormal ofdas proteínas tau inno Alzheimer's diseasealzéimer.<ref name="pmid7838376">{{cite journal |author=Gong CX, Grundke-Iqbal I, Iqbal K |title=Dephosphorylation of Alzheimer's disease abnormally phosphorylated tau by protein phosphatase-2A |journal=Neuroscience |volume=61 |issue=4 |pages=765–72 |date=August 1994 |pmid=7838376 |doi= 10.1016/0306-4522(94)90400-6|url=}}</ref>
Dephosphorylation has also been linked to [[cardiac disease]], particularly the alteration of actin-myosin interactions that are key for providing the underlying force of a heartbeat. Dephosphorylation is a key part of the myosin cycling kinetics that directly control the actin-myosin interactions. When the dephosphorylation process is interrupted, calcium dependent cardiac contraction is impaired or fully disabled.<ref name="pmid22426213">{{cite journal |author=Sheikh F, Ouyang K, Campbell SG |title=Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease |journal=J. Clin. Invest. |volume=122 |issue=4 |pages=1209–21 |date=April 2012 |pmid=22426213 |pmc=3314469 |doi=10.1172/JCI61134 |url=|display-authors=etal}}</ref>
 
ResearchA hasdesfosforilación alsotamén suggestedestá thatligada modificationscon todoenzas dephosphorylationcardíacas, impactespecialmente physiologicala processesalteración implicatedde ininteraccións [[Diabetes mellitusactina]].-[[miosina]], Theque kineticsson ofclaves dephosphorylationpara ofproporcionar insulina receptorforza substrate-1/2,necesaria Akt,para ando ERK1/2,latexo phosphoproteinscardíaco. areA showndesfosforilación toé beunha involvedparte infundamental insulinda receptorcinética signaling,do andciclo ''inda vitro''miosina modelsque demonstratecontrola thatdirectamente changesas tointeraccións dephosphorylationactina-miosina. kineticsCando impactse upstraminterrompe ando proceso de desfosforilación, a contracción cardíaca dependente de calcio está alterada downstreamou insulincompletamente stimulationinactivada.<ref name="pmid17068339pmid22426213">{{cite journal |author=ZhandeSheikh RF, ZhangOuyang WK, ZhengCampbell YSG |title=DephosphorylationMouse byand default,computational amodels potentiallink mechanismMlc2v fordephosphorylation regulationto ofaltered insulinmyosin receptorkinetics substrate-1/2,in Akt,early andcardiac ERK1/2disease |journal=J. BiolClin. ChemInvest. |volume=281122 |issue=514 |pages=39071–801209–21 |date=DecemberApril 20062012 |pmid=1706833922426213 |pmc=3314469 |doi=10.10741172/jbc.M605251200JCI61134 |url=|display-authors=etal}}</ref>
 
Algunhas investigacións tamén indican que as modificacións da desfosforilación inflúen en procesos fisiolóxicos envolvidos na [[diabetes mellitus]]. A cinética da desfosforilación das fosfoproteínas do [[receptor da insulina]] substrato-1/2, Akt, e ERK1/2 está implicada na sinalización do receptor da insulina, e os modelos ''in vitro'' demostran que os cambios na cinética da desfosforilación inflúen na estimulación da insulina ''[[augas arriba]]'' e ''augas abaixo''.<ref name="pmid17068339">{{cite journal |author=Zhande R, Zhang W, Zheng Y |title=Dephosphorylation by default, a potential mechanism for regulation of insulin receptor substrate-1/2, Akt, and ERK1/2 |journal=J. Biol. Chem. |volume=281 |issue=51 |pages=39071–80 |date=December 2006 |pmid=17068339 |doi=10.1074/jbc.M605251200 |url=|display-authors=etal}}</ref>
 
=== Tratamentos ===
 
Inhibition of proton pumps<ref name="Robinson 709-15"/> significantly decreases the acidity of the gastrointestinal tract, reducing the symptoms of acid-related diseases. The resulting change in pH decreases survival of the bacteria ''H.pylori'', a major cause of peptic ulcer disease. Once the proton pump inhibitor eradicates this bacteria within the gut, reversing erosive reflux.
A inhibición da bomba de protóns<ref name="Robinson 709-15"/> fai diminuír significativamente a acidez do tracto gastrointestinal, reducindo os síntomas de enfermidades relacionadas coa acidez. O cambio resultante no [[pH]] fai diminuír a supervivencia da bacteria ''[[Helicobacter pylori|H. pylori'', unha causa principal das úlceras a pépticas. Unha vez que o inhibidor da bomba de protóns erradica esta bacteria do estómago (para o cal poden ser necesarios tamén tratamentos con [[antibiótico]]s), revértese o refluxo erosivo.
Treating heart disease has improved with the use of drugs that inhibit [[AMP-activated protein kinase|AMPK]] via dephosphorylation.<ref>{{cite journal|last=Hutchinson|first=DS|author2=Summers, RJ |author3=Bengtsson, T |title=Regulation of AMP-activated protein kinase activity by G-protein coupled receptors: potential utility in treatment of diabetes and heart disease.|journal=Pharmacology & therapeutics|date=Sep 2008|volume=119|issue=3|pages=291–310|pmid=18606183|doi=10.1016/j.pharmthera.2008.05.008}}</ref>
InO thetratamento treatmentdas ofenfermidades diabetes,cardíacas [[sulfonylurea]]mellorou drugsco areuso ablede tofármacos stimulateque dephosphorylationinhiben of the glucose transportera [[GLUT4]],proteína decreasingquinase insulinactivada resistancepor andAMP|AMPK]] increasingpor andmedio glucosede utilizationdesfosforilación.<ref>{{cite journal|last=MüllerHutchinson|first=GDS|author2=WiedSummers, SRJ |author3=Bengtsson, T |title=TheRegulation sulfonylureaof drug,AMP-activated glimepiride,protein stimulateskinase glucoseactivity transport,by glucoseG-protein transportercoupled translocation,receptors: andpotential dephosphorylationutility in insulin-resistanttreatment ratof adipocytesdiabetes inand vitroheart disease.|journal=DiabetesPharmacology & therapeutics|date=DecSep 19932008|volume=42119|issue=123|pages=1852–67291–310|pmid=824383218606183|doi=10.23371016/diabetesj.42pharmthera.122008.185205.008}}</ref>
No tratamento do diabetes, o fármaco [[sulfonilurea]] pode estimular a desfosforilación do transportador de glicosa [[GLUT4]], diminuíndo así a resistencia á [[insulina]] e aumentando a utilización de[[glicosa]].<ref>{{cite journal|last=Müller|first=G|author2=Wied, S|title=The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro.|journal=Diabetes|date=Dec 1993|volume=42|issue=12|pages=1852–67|pmid=8243832|doi=10.2337/diabetes.42.12.1852}}</ref>
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== Aplicacións en investigación ==
A desfosforilación xogsa un papel clave en bioloxóa molecular, especialmente na [[clonación molecular|clonación]] usando [[encima de restrición|encimas de restrición]]. Os extremos cortados dun [[vector de clonación|vector]] poden vlverse a unir durante o paso de ligación debido á fosforilación. Pode evitarse que estes extremos se volvan a unir usando unha fosfatase desfortalizante.<ref name="Cloning manual">{{cite book|last=Sambrook|first=J|title=Molecular Cloning: A Laboratory Manual|year=1989|publisher=Cold Spring Harbor Laboratory Press|edition=2nd|author2=Fritsch, E.F.|author3=Maniatis, T.}}</ref> Estas [[fosfatase alcalina|fosfatases alcalinas]] utilizadas proceden xeralmente do intestino de tenreira, e denominanse abreviadamente CIP (''Calf-intestinal alkaline phosphatase'', fosfatase alcalina de intestino de tenreira).<ref name="pmid19838171">{{cite journal |author=Makovets S, Blackburn EH |title=DNA damage signalling prevents deleterious telomere addition at DNA breaks |journal=Nat. Cell Biol. |volume=11 |issue=11 |pages=1383–6 |date=November 2009 |pmid=19838171 |pmc=2806817 |doi=10.1038/ncb1985 |url=}}</ref>