{"id":60378,"date":"2007-10-09T00:00:00","date_gmt":"2007-10-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/importancia-de-la-biosa%c2%adntesis-del-ergosterol-en-la-proliferacion-celular-y-en-el-mecanismo-de-accion-de-farmacos-en-tripanosomatidos\/"},"modified":"2007-10-09T00:00:00","modified_gmt":"2007-10-09T00:00:00","slug":"importancia-de-la-biosa%c2%adntesis-del-ergosterol-en-la-proliferacion-celular-y-en-el-mecanismo-de-accion-de-farmacos-en-tripanosomatidos","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica-molecular\/importancia-de-la-biosa%c2%adntesis-del-ergosterol-en-la-proliferacion-celular-y-en-el-mecanismo-de-accion-de-farmacos-en-tripanosomatidos\/","title":{"rendered":"Importancia de la bios\u00edntesis del ergosterol en la proliferaci\u00f3n celular y en el mecanismo de acci\u00f3n de f\u00e1rmacos en tripanosom\u00e1tidos"},"content":{"rendered":"<h2>Tesis doctoral de <strong>  Sealey Cardona Marco Roberto <\/strong><\/h2>\n<p>La ruta de bios\u00edntesis de esteroles en tripanosom\u00e1tidos constituye un atractivo conjunto de dianas de acci\u00f3n farmacol\u00f3gica y compuestos inhibidores de la misma han demostrado su eficacia en la interrupci\u00f3n del crecimiento de distintos protozoos pat\u00f3genos. Uno de los principales objetivos de este trabajo ha sido la obtenci\u00f3n de un sistema de expresi\u00f3n heter\u00f3logo de prote\u00edna soluble y activa para la sqs de trypanosoma cruzi. Los resultados obtenidos en esta tesis claramente demuestran que la eliminaci\u00f3n de amino\u00e1cidos de la regiones amino y carboxilo terminal generan prote\u00edna soluble y activa. Las km para sus sustratos fpp y nadph fueron de 5.25 \u00c2\u00b5m y 24.47 \u00c2\u00b5m respectivamente y la vmax de 1428.56 nmol.Min.Mg-1. Estudios de inhibici\u00f3n frente a derivados de quinuclidinas y ensayos comparativos con la sqs humana nos permitieron identificar varias quinuclidinas selectivas y muy potentes con valores de ki del orden nm frente a la sqs de t. Cruzi.  por otro lado se ha estudiado el papel de la enzima 24-esterol metiltransferasa de trypanosoma brucei y el mecanismo de acci\u00f3n de los azasteroles. Se sintetizaron un grupo de azasteroles que resultaron poseer una potente actividad, del orden de nm, in vitro frente a cultivos de las formas sangu\u00edneas de t. B. Rhodesiense. Sin embargo, pudimos determinar que estos azasteroles no eran activos frente a la enzima recombinante 24-esterol metiltransferasa de trypanosoma brucei. A su vez, estudios de la composici\u00f3n lip\u00eddica de las formas sangu\u00edneas y proc\u00edclicas de trypanosoma brucei revelaron que las formas sangu\u00edneas del par\u00e1sito poseen mayoritariamente esteroles de tipo colesta mientras que los proc\u00edclicos poseen esteroles de tipo ergosta. Estudios de northen y western blot afirmaron la presencia de la enzima en ambas formas del par\u00e1sito. Concluimos que en la cititoxicidad de los azasteroles sintetizados est\u00e1n implicados procesos moleculares adicionales a la inhibici\u00f3n de la 24-esterol metiltransferasa de t<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Importancia de la bios\u00edntesis del ergosterol en la proliferaci\u00f3n celular y en el mecanismo de acci\u00f3n de f\u00e1rmacos en tripanosom\u00e1tidos<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Importancia de la bios\u00edntesis del ergosterol en la proliferaci\u00f3n celular y en el mecanismo de acci\u00f3n de f\u00e1rmacos en tripanosom\u00e1tidos <\/li>\n<li><strong>Autor:<\/strong>\u00a0  Sealey Cardona Marco Roberto <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Granada<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 10\/09\/2007<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Dolores Gonz\u00e1lez Pacanowska<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Francisco Miguel Canovas ramos <\/li>\n<li>angel Navarro Miguel (vocal)<\/li>\n<li> Marco de la calle carmen (vocal)<\/li>\n<li>Manuel Estevez Antonio (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Sealey Cardona Marco Roberto La ruta de bios\u00edntesis de esteroles en tripanosom\u00e1tidos constituye un atractivo conjunto de [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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