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

A. Hernández-Vázquez*, B. Wolf, K. Pindolia, D. Ortega-Cuellar, R. Hernández-González, A. Heredia-Antúnez, I. Ibarra-González, A. Velázquez-Arellano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 (ε-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.

Original languageEnglish (US)
Pages (from-to)248-254
Number of pages7
JournalMolecular Genetics and Metabolism
Volume110
Issue number3
DOIs
StatePublished - Nov 2013

Keywords

  • AMPK
  • Biotin deficiency
  • Biotinidase knockout
  • Energetic deficit
  • Insulin sIgnaling pathway
  • Insulin sensitivity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this