| First Author | Hernández-Vázquez A | Year | 2013 |
| Journal | Mol Genet Metab | Volume | 110 |
| Issue | 3 | Pages | 248-54 |
| PubMed ID | 24075304 | Mgi Jnum | J:205291 |
| Mgi Id | MGI:5544528 | Doi | 10.1016/j.ymgme.2013.08.018 |
| Citation | Hernandez-Vazquez A, et al. (2013) 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. Mol Genet Metab 110(3):248-54 |
| abstractText | 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 (epsilon-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. |
