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
| Autor: | A. Heredia-Antúnez, Barry Wolf, Antonio Velázquez-Arellano, Kirit Pindolia, Daniel Ortega-Cuellar, Alain de J. Hernandez-Vazquez, R. Hernández-González, Isabel Ibarra-González |
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| Rok vydání: | 2013 |
| Předmět: |
Adenosine monophosphate
Blood Glucose Endocrinology Diabetes and Metabolism Biotin deficiency Biotin Gene Expression Biology Biochemistry chemistry.chemical_compound Mice Endocrinology Biocytin Carnitine Genetics medicine Animals Humans RNA Messenger Protein kinase A Molecular Biology Mice Knockout Biotinidase Deficiency Biotinidase deficiency Body Weight medicine.disease Carbon Pyruvate carboxylase Diet Disease Models Animal chemistry Liver Biotinidase Energy Metabolism |
| Zdroj: | Molecular genetics and metabolism. 110(3) |
| ISSN: | 1096-7206 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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