{"id":13123,"date":"2001-02-10T00:00:00","date_gmt":"2001-02-10T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/factores-estructurales-que-regulan-la-actividad-de-la-metionina-adenosiltransferasa-hepatica\/"},"modified":"2001-02-10T00:00:00","modified_gmt":"2001-02-10T00:00:00","slug":"factores-estructurales-que-regulan-la-actividad-de-la-metionina-adenosiltransferasa-hepatica","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/factores-estructurales-que-regulan-la-actividad-de-la-metionina-adenosiltransferasa-hepatica\/","title":{"rendered":"Factores estructurales que regulan la actividad de la metionina adenosiltransferasa hep\u00e1tica"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Isabel P\u00e9rez Mato <\/strong><\/h2>\n<p>La metionina adenosiltransferasa (mat) juega un papel central en el metabolismo celular, ya que sintetiza a partir de atp y metionina, s-adenosilmetionina (adomet), el principal donante de metilos de la c\u00e9lula. La actividad de la mat ha de ser regulada con precisi\u00f3n para asegurar la provisi\u00f3n de adomet pero evitar un consumo innecesario de atp. La regulaci\u00f3n de la mat hep\u00e1tica a\u00fan no se conoce bien, pero se ha determinado, tanto in vivo como in vitro, que la enzima es inactivada por \u00f3xido n\u00edtrico, mediante la s-nitrosilaci\u00f3n de la ciste\u00edna 121. En este estudio se demuestra que la sustituci\u00f3n por serina de residuos \u00e1cidos y b\u00e1sicos localizados en el microentorno de la ciste\u00edna 121, produce formas de la enzima que son menos sensibles a la s-nitrosilaci\u00f3n e inactivaci\u00f3n por \u00f3xido n\u00edtrico. Estos experimentos aportan la primera evidencia experimental de que los amino\u00e1cidos cargados del entorno a la ciste\u00edna diana gobiernan la s-nitrosilaci\u00f3n de prote\u00ednas.  los individuos con mutaciones en el gen mat 1a, que codifica la mat hep\u00e1tica, presentan una reducci\u00f3n en la actividad de esta enzima, lo que les causa una hipermetioninemia persistente. El fenotipo de hipermetininemia asociado a estas mutaciones es heredado de forma autos\u00f3mica recesiva, con la \u00fanica excepci\u00f3n de la transici\u00f3n g-a en el nucle\u00f3tido 791 del ex\u00f3n vii, una mutaci\u00f3n que genera la variante r264h de la mat y que presenta un patr\u00f3n de herencia autos\u00f3mica dominante. En este estudio, se demuestra que la mutaci\u00f3n equivalente en la mat de h\u00edgado de rata resulta en una forma monom\u00e9rica de la enzima que carece de actividad de s\u00edntesis de adomet. Adem\u00e1s, esta subunidad mutada es capaz de asociarse con subunidades nativas, secuestr\u00e1ndolas en un heterod\u00edmero incapaz de sintetizar adomet. Estos resultados proveen un mecanismo molecular que explica la herencia autos\u00f3mica dominante del fenotipo asociado a esta mutaci\u00f3n.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Factores estructurales que regulan la actividad de la metionina adenosiltransferasa hep\u00e1tica<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Factores estructurales que regulan la actividad de la metionina adenosiltransferasa hep\u00e1tica <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Isabel P\u00e9rez Mato <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 02\/10\/2001<\/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>Fernando Jose Corrales Izquierdo<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Francisco Borras cuesta <\/li>\n<li>mat\u00edas Antonio \u00e1vila zaragoz\u00e1 (vocal)<\/li>\n<li>Santiago Lamas pel\u00e1ez (vocal)<\/li>\n<li>susana Alemany de la pe\u00f1a (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Isabel P\u00e9rez Mato La metionina adenosiltransferasa (mat) juega un papel central en el metabolismo celular, ya 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 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