{"id":69836,"date":"2004-07-09T00:00:00","date_gmt":"2004-07-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/variantes-de-splicing-y-estructura-tridimensional-de-la-enzima-hmg-coaliasa-humana-caracterizacion-molecular-y-funcional-de-cuatro-nuevasvariantes-alelicas\/"},"modified":"2004-07-09T00:00:00","modified_gmt":"2004-07-09T00:00:00","slug":"variantes-de-splicing-y-estructura-tridimensional-de-la-enzima-hmg-coaliasa-humana-caracterizacion-molecular-y-funcional-de-cuatro-nuevasvariantes-alelicas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/zaragoza\/variantes-de-splicing-y-estructura-tridimensional-de-la-enzima-hmg-coaliasa-humana-caracterizacion-molecular-y-funcional-de-cuatro-nuevasvariantes-alelicas\/","title":{"rendered":"Variantes de splicing y estructura tridimensional de la enzima hmg-coaliasa humana. caracterizaci\u00f3n molecular y funcional de cuatro nuevasvariantes al\u00e9licas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Beatriz Puisac Uriol <\/strong><\/h2>\n<p>El gen hmgcl codifica la enzima 3-hidroxi-3-metilglutaril coa (hmg-coa) liasa (hl; ec 4.1.3.4) que interviene en el catabolismo de la leucina y en la s\u00edntesis de cuerpos cet\u00f3nicos. Este trabajo aporta el primer estudio completo y sistem\u00e1tico de las variantes de splicing fisiol\u00f3gicas de este gen. Se han caracterizado dos variantes, una con deleci\u00f3n de los exones 5 y 6 y otra con deleci\u00f3n de los exones 5, 6 y 7, ambas sin actividad enzim\u00e1tica. Por pcr en tiempo real se han cuantificado en distintos tejidos adultos y fetales. Los valores m\u00e1s altos han aparecido en tejidos no cetog\u00e9nicos como m\u00fasculo esquel\u00e9tico, coraz\u00f3n y cerebro. Se sugiere que la producci\u00f3n de variantes de splicing inactivas tal vez act\u00faa como un mecanismo de regulaci\u00f3n negativa de la enzima. El grado de desarrollo no parece influir en la proporci\u00f3n por tejidos de las variantes de splicing. la deficiencia de la hmg-coa liasa (mckusick 24645, mim 246450) ha sido estudiada a nivel molecular en 42 pacientes, habi\u00e9ndose descrito 26 variantes al\u00e9licas diferentes. Este trabajo aporta 5 nuevos casos y 4 nuevas variantes al\u00e9licas. Entre ellas una nueva mutaci\u00f3n de splicing y el primer caso de mutaciones en cis de este gen. Adem\u00e1s, el hallazgo de un nuevo caso de mutaci\u00f3n mediterr\u00e1nea, confirma a esta, como la segunda en frecuencia a nivel mundial (15,9%) y la predominante en la pen\u00ednsula ib\u00e9rica (83,3 %). se propone tambi\u00e9n por primera vez un modelo de estructura tridimensional para la hmg? coa liasa en forma de tim barrel con 8 h\u00e9lices alfa y 8 l\u00e1minas beta. El modelo se basa en la similitud con otras estructuras tim barrel de prote\u00ednas funcionalmente relacionadas, en la localizaci\u00f3n de los amino\u00e1cidos catal\u00edticos del centro activo, y en la coincidencia de formas entre el sustrato (hmg-coa) y la cavidad predicha. La mayor\u00eda de las mutaciones descritas est\u00e1n localizadas alrededor del canal del sustrato, produciendo algunas de ellas su obstrucci\u00f3n (s75r<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Variantes de splicing y estructura tridimensional de la enzima hmg-coaliasa humana. caracterizaci\u00f3n molecular y funcional de cuatro nuevasvariantes al\u00e9licas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Variantes de splicing y estructura tridimensional de la enzima hmg-coaliasa humana. caracterizaci\u00f3n molecular y funcional de cuatro nuevasvariantes al\u00e9licas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Beatriz Puisac Uriol <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Zaragoza<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 07\/09\/2004<\/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>Juan Pie Juste<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: fausto Garcia hegardt <\/li>\n<li>paulino Gomez puertas (vocal)<\/li>\n<li>n\u00faria Casals farr\u00e9 (vocal)<\/li>\n<li>Carlos Mart\u00edn monta\u00f1\u00e9s (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Beatriz Puisac Uriol El gen hmgcl codifica la enzima 3-hidroxi-3-metilglutaril coa (hmg-coa) liasa (hl; ec 4.1.3.4) que [&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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[13610],"tags":[152744,7141,400,17493,19833,65973],"class_list":["post-69836","post","type-post","status-publish","format-standard","hentry","category-zaragoza","tag-beatriz-puisac-uriol","tag-carlos-martin-montanes","tag-fausto-garcia-hegardt","tag-juan-pie-juste","tag-nuria-casals-farre","tag-paulino-gomez-puertas"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/69836","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=69836"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/69836\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=69836"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=69836"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=69836"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}