Ácido micólico: Diferenzas entre revisións

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Miguelferig (conversa | contribucións)
Miguelferig (conversa | contribucións)
Liña 10:
 
A presenza de ácidos micólicos dálle a ''M. tuberculosis'' moitas características que a fan resistente a moitos tratamenteos médicos. Danlle á bacteria unha maior resistencia aos danos químicos e á deshidratación, e impiden a actividade efectiva dos [[antibiótico]]s [[hidrofóbico]]s. Ademais, os ácidos micólicos permítenlle á bacteria crecer facilmente no interios dos [[macrófago]]s (que as [[fagocitose|fagocitaron]]), ao facelas indetectables polo [[sistema inmunitario]] do [[hóspede]]. A biosíntese de micolatos é crucial para a supervivencia e patoxénese de ''M. tuberculosis''. A vía de síntese e os [[encima]]s utilizados coñécense en detalle.<ref> Takayama, K.; Wang, C.; Besra, G. S. (2005). "Pathway to Synthesis and Processing of Mycolic Acids in Mycobacterium tuberculosis". Clinical Microbiology Reviews 18 (1): 81–101. doi:10.1128/CMR.18.1.81-101.2005. PMC 544180. PMID 15653820.</ref><ref> Raman, K.; Rajagopalan, P.; Chandra, N. (2005). "Flux Balance Analysis of Mycolic Acid Pathway: Targets for Anti-Tubercular Drugs". PLoS Computational Biology 1 (5): e46. doi:10.1371/journal.pcbi.0010046. PMC 1246807. PMID 16261191.</ref> A vía ten cinco pasos, que se resumen como segue:<ref> Bhatt, A.; Molle, V.; Besra, G. S.; Jacobs, W. R.; Kremer, L. (2007). "The Mycobacterium tuberculosis FAS-II condensing enzymes: Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development". Molecular Microbiology 64 (6): 1442–1454. doi:10.1111/j.1365-2958.2007.05761.x. PMID 17555433.</ref>
* SynthesisSíntese ofde theácidos C26graxos saturatedde straightcadea chainrecta fattysaturados acidsde by26 thecarbonos enzymepolo encima [[fattyácido acidgraxo synthasesintase]]-I (FAS-I) topara provideproporcionar thea rama α-alkyl branch ofalquilo thedos mycolicácidos acids;micólicos.
* Síntese de ácidos graxos de 56 carbonos polo encima FAS-II para proporcionar o esqueleto de meromicolato.
* Synthesis of the C56 fatty acids by FAS-II providing the meromycolate backbone;
* Introdución de grupos funcionais á cadea de meromicolato por parte de numerosas ciclopropano sintases.
* Introduction of functional groups to the meromycolate chain by numerous cyclopropane synthases;
* CondensationReacción reactionde catalysedcondensación by[`catálise|catalizada]] thepola [[polyketidepolicétido synthasesintase]] Pks13 betweenentre thea rama α-branch ande thea meromycolatecadea chainde beforemeromicolato aantes finalda reductionredución byfinal thepolo enzymeencima corynebacterineae mycolatemicolato reductaseredutase A (CmrA)<ref>{{cite journal|last=David J|first=Lea-Smith J|coauthors=James S. Pyke, Dedreia Tull, Malcolm J. McConville, Ross L. Coppel and Paul K. Crellin|title=The Reductase That Catalyzes Mycolic Motif Synthesis Is Required for Efficient Attachment of Mycolic Acids to Arabinogalactan|journal=Journal of Biological Chemistry|year=2007|volume=282|issue=15|pages=11000–11008|doi=10.1074/jbc.M608686200|pmid=17308303}}</ref> topara generatexerar theo mycolicácido acid;micólico anddefinitivo.
* Transferencia de ácidos micólicos ao [[arabinogalactano]] e outros aceptores como a [[trehalosa]] por medio do complexo do antíxeno 85.
* Transfer of mycolic acids to arabinogalactan and other acceptors such as trehalose via the antigen 85 complex
 
As vías da ácido graxo sintase-I e a ácido graxo sintase-II produtoras de ácidos micólicos están ligadas polo encima [[beta-cetoacil-(proteína portadora de acilos) sintase III]], xeralmente designada mtFabH. Novos inhibidores deste encima poderían potencialmente usarse como axentes terapéuticos.
The fatty acid synthase-I and fatty acid synthase-II pathways producing mycolic acids are linked by the [[beta-ketoacyl-(acyl-carrier-protein) synthase III]] enzyme, often designated as mtFabH. Novel inhibitors of this enzyme could potentially be used as therapeutic agents.
 
The mycolic acids show interesting inflammation controlling properties. A clear tolerogenic response was promoted by natural mycolic acids in experimental [[asthma]].<ref>{{pmid|16675779}}</ref> The natural extracts are however chemically heterogeneous and inflammatory. By [[organic synthesis]], the different homologues from the natural mixture could be obtained in pure form and tested for biological activity. One subclass proved to be a very good suppressor of asthma, through a totally new mode of action. These compounds are now under further investigation. A second subclass triggered a [[cell (biology)|cell]]ular immune response ([[Th1 cell|Th1]] and [[Th17]]), so studies are ongoing to use this subclass as an [[adjuvant]] for [[vaccination]].