Novel roles of holocarboxylase synthetase in gene regulation and intermediary metabolism

Nutr Rev. 2014 Jun;72(6):369-76. doi: 10.1111/nure.12103. Epub 2014 Mar 28.

Abstract

The role of holocarboxylase synthetase (HLCS) in catalyzing the covalent binding of biotin to the five biotin-dependent carboxylases in humans is well established, as are the essential roles of these carboxylases in the metabolism of fatty acids, the catabolism of leucine, and gluconeogenesis. This review examines recent discoveries regarding the roles of HLCS in assembling a multiprotein gene repression complex in chromatin. In addition, emerging evidence suggests that the number of biotinylated proteins is far larger than previously assumed and includes members of the heat-shock superfamily of proteins and proteins coded by the ENO1 gene. Evidence is presented linking biotinylation of heat-shock proteins HSP60 and HSP72 with redox biology and immune function, respectively, and biotinylation of the two ENO1 gene products MBP-1 and ENO1 with tumor suppression and glycolysis, respectively.

Keywords: chromatin; epigenetics; gene regulation; holocarboxylase synthetase; metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Biotin / genetics*
  • Biotin / metabolism
  • Biotinylation
  • Carbon-Nitrogen Ligases / genetics*
  • Carbon-Nitrogen Ligases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Gene Expression*
  • Glycolysis / genetics*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • Myelin Basic Protein
  • Tumor Suppressor Proteins
  • Biotin
  • ENO1 protein, human
  • Phosphopyruvate Hydratase
  • Carbon-Nitrogen Ligases
  • holocarboxylase synthetases