Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation: Clues for the pathogenesis in the human inherited disorder
Por:
Hernández-Vázquez A., Wolf B., Pindolia K., Ortega-Cuellar D., Hernández-González R., Heredia-Antúnez A., Ibarra-González I., Velázquez-Arellano A.
Publicada:
1 nov 2013
Resumen:
Biotin is the prosthetic group of carboxylases that have important roles in the metabolism of glucose, fatty acids and amino acids. Biotinidase has a key role in the reutilization of the biotin, catalyzing the hydrolysis of biocytin (e-N-biotinyl- l-lysine) and biocytin-containing peptides derived from carboxylase turnover, thus contributing substantially to the bioavailability of this vitamin. Deficient activity of biotinidase causes late-onset multiple carboxylase in humans, whose pathogenic mechanisms are poorly understood. Here we show that a knock-out biotinidase-deficient mouse from a C57BL/6 background that was fed a low biotin diet develops severe ATP deficit with activation of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK), inhibition of the signaling protein mTOR, driver of protein synthesis and growth, and affecting the expression of central-carbon metabolism genes. In addition, sensitivity to insulin is augmented. These changes are similar to those observed in nutritionally biotin-starved rats. These findings further our understanding of the pathogenesis of human biotinidase deficiency. © 2013 Elsevier Inc.
Filiaciones:
Hernández-Vázquez A.:
Univ Nacl Autonoma Mexico, Inst Natl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
Wolf B.:
Henry Ford Hospital, Department of Medical Genetics, Detroit, MI, United States
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, United States
Pindolia K.:
Henry Ford Hospital, Department of Medical Genetics, Detroit, MI, United States
Ortega-Cuellar D.:
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, México City, Mexico
Hernández-González R.:
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Heredia-Antúnez A.:
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Ibarra-González I.:
Univ Nacl Autonoma Mexico, Inst Natl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
Velázquez-Arellano A.:
Univ Nacl Autonoma Mexico, Inst Natl Pediat, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
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