{"id":5000,"date":"2018-12-04T09:25:52","date_gmt":"2018-12-04T08:25:52","guid":{"rendered":"http:\/\/bifi.es\/?p=5000"},"modified":"2018-12-04T09:29:14","modified_gmt":"2018-12-04T08:29:14","slug":"articulo-de-los-investigadores-del-bifi-pedro-latorre-y-jose-alberto-carrodeguas-publicado-en-molecular-cell-ha-sido-reconocido-como-articulo-del-mes-por-a-sociedad-espanola-de-bioquimica-y-biologia-m","status":"publish","type":"post","link":"https:\/\/bifi.es\/es\/articulo-de-los-investigadores-del-bifi-pedro-latorre-y-jose-alberto-carrodeguas-publicado-en-molecular-cell-ha-sido-reconocido-como-articulo-del-mes-por-a-sociedad-espanola-de-bioquimica-y-biologia-m\/","title":{"rendered":"Art\u00edculo de los investigadores del BIFI Pedro Latorre y Jos\u00e9 Alberto Carrodeguas publicado en Molecular Cell ha sido reconocido como art\u00edculo del mes por a Sociedad Espa\u00f1ola de Bioqu\u00edmica y Biolog\u00eda Molecular (SEBBM)"},"content":{"rendered":"

El art\u00edculo publicado en Molecular Cell por los\u00a0investigadores del BIFI Pedro Latorre y Jos\u00e9 Alberto Carrodeguas<\/strong> titulado Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions, <\/em>ha sido reconocido como art\u00edculo del mes por a Sociedad Espa\u00f1ola de Bioqu\u00edmica y Biolog\u00eda Molecular (SEBBM).<\/strong><\/p>\n

Resumen<\/p>\n

La fosfoenolpiruvato carboxiquinasa citos\u00f3lica (PCK1) se encuentra en un cruce de camino de numerosas rutas metab\u00f3licas y cataliza una reacci\u00f3n reversible. El papel biol\u00f3gico de PCK1 ha estado asociado al de la gluconeog\u00e9nesis (una de las reacciones), sin embargo, el papel de la reacci\u00f3n reversa en mam\u00edferos es desconocido. Latorre y cols. describen los mecanismos por los que diversas modificaciones post-traduccionales (PTMs) son capaces de regular tanto la actividad como la estabilidad de la PCK1. En condiciones de alta glucosa, la acetilaci\u00f3n de PCK1 favorece la reacci\u00f3n reversa de la enzima que permite suministrar metabolitos al ciclo de Krebs. En estas mismas condiciones, la fosforilaci\u00f3n de PCK1 es mediada por GSK3\u03b2 y favorece la ubiquitinaci\u00f3n y degradaci\u00f3n de la enzima no acetilada. Por otro lado, en condiciones de baja glucosa, SIRT1 deacetila PCK1 y restaura las propiedades cin\u00e9ticas de la enzima favoreciendo la ruta gluconeog\u00e9nica. Esta reacci\u00f3n de deacetilaci\u00f3n se ve facilitada por la fosforilaci\u00f3n de ciertos residuos. En conjunto, la acetilaci\u00f3n, fosforilaci\u00f3n y ubiquitinaci\u00f3n de PCK1 interact\u00faan con el fin de controlar la estabilidad y el sentido de la reacci\u00f3n de la enzima en funci\u00f3n de las condiciones energ\u00e9ticas de las c\u00e9lulas.<\/span><\/span><\/p>\n

Summary<\/p>\n

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts the enzyme between gluconeogenic and anaplerotic activities. Under high glucose, p300-dependent hyperacetylation of PCK1 did not lead to protein degradation but instead increased the ability of PCK1 to perform the anaplerotic reaction, converting phosphoenolpyruvate to oxaloacetate. Lys91 acetylation destabilizes the active site of PCK1 and favors the reverse reaction. At low energy input, we demonstrate that SIRT1 deacetylates PCK1 and fully restores the gluconeogenic ability of PCK1. Additionally, we found that GSK3\u03b2-mediated phosphorylation of PCK1 decreases acetylation and increases ubiquitination. Biochemical evidence suggests that serine phosphorylation adjacent to Lys91 stimulates SIRT1-dependent deacetylation of PCK1. This work reveals an unexpected capacity of hyperacetylated PCK1 to promote anaplerotic activity, and the intersection of post-translational control of PCK1 involving acetylation, phosphorylation, and ubiquitination. <\/span><\/span><\/p>\n

Referencia<\/h3>\n

Latorre-Muro, P., Baeza, J., Armstrong, E. A., Hurtado-Guerrero, R., Corzana, F., Wu, L.E., Sinclair, D.A., L\u00f3pez-Buesa, P., Carrodeguas, J.A., Denu, J.M. (2018). Dynamic acetylation of cytosolic phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions. Mol. Cell 71, 718-732. doi: 10.1016\/j.molcel.2018.07.031. dynamic_acetylation_article<\/a><\/span><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

El art\u00edculo publicado en Molecular Cell por los\u00a0investigadores del BIFI Pedro Latorre y Jos\u00e9 Alberto Carrodeguas titulado Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions, […]<\/p>\n","protected":false},"author":8,"featured_media":5006,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[30,47],"tags":[],"class_list":["post-5000","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticias-es","category-noticias-es-2"],"_links":{"self":[{"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/posts\/5000","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/comments?post=5000"}],"version-history":[{"count":1,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/posts\/5000\/revisions"}],"predecessor-version":[{"id":5005,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/posts\/5000\/revisions\/5005"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/media\/5006"}],"wp:attachment":[{"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/media?parent=5000"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/categories?post=5000"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bifi.es\/es\/wp-json\/wp\/v2\/tags?post=5000"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}