English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/143652
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Título

Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism

AutorMesa-Torres, Noel; Calvo, Ana C.; Oppici, Elisa; Titelbaum, Nicholas; Montioli, Riccardo; Miranda-Vizuete, Antonio ; Cellini, Barbara; Salido, Eduardo; Pey, Ángel L.
Palabras clavePrimary hyperoxaluria
Protein stability
Conformational disease
Substrate specificity
Enzyme kinetics
Fecha de publicaciónsep-2016
EditorElsevier
CitaciónBiochimica et Biophysica Acta - Proteins and Proteomics 1864(9): 1195- 1205 (2016)
ResumenIn humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity.
Versión del editorhttp://doi.org/10.1016/j.bbapap.2016.05.004
URIhttp://hdl.handle.net/10261/143652
DOI10.1016/j.bbapap.2016.05.004
Identificadoresissn: 1878-1454
Aparece en las colecciones: (IBIS) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
10261_143652.pdf1,64 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.