Structure and function of biotin-dependent carboxylases

Cell Mol Life Sci. 2013 Mar;70(5):863-91. doi: 10.1007/s00018-012-1096-0. Epub 2012 Aug 7.


Biotin-dependent carboxylases include acetyl-CoA carboxylase (ACC), propionyl-CoA carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase (MCC), geranyl-CoA carboxylase, pyruvate carboxylase (PC), and urea carboxylase (UC). They contain biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl carrier protein components. These enzymes are widely distributed in nature and have important functions in fatty acid metabolism, amino acid metabolism, carbohydrate metabolism, polyketide biosynthesis, urea utilization, and other cellular processes. ACCs are also attractive targets for drug discovery against type 2 diabetes, obesity, cancer, microbial infections, and other diseases, and the plastid ACC of grasses is the target of action of three classes of commercial herbicides. Deficiencies in the activities of PCC, MCC, or PC are linked to serious diseases in humans. Our understanding of these enzymes has been greatly enhanced over the past few years by the crystal structures of the holoenzymes of PCC, MCC, PC, and UC. The structures reveal unanticipated features in the architectures of the holoenzymes, including the presence of previously unrecognized domains, and provide a molecular basis for understanding their catalytic mechanism as well as the large collection of disease-causing mutations in PCC, MCC, and PC. This review will summarize the recent advances in our knowledge on the structure and function of these important metabolic enzymes.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acetyl-CoA Carboxylase / chemistry
  • Acetyl-CoA Carboxylase / metabolism*
  • Animals
  • Biotin / metabolism*
  • Carbon-Carbon Ligases / chemistry
  • Carbon-Carbon Ligases / metabolism*
  • Carbon-Nitrogen Ligases / chemistry
  • Carbon-Nitrogen Ligases / metabolism*
  • Fatty Acid Synthase, Type II / chemistry
  • Fatty Acid Synthase, Type II / metabolism
  • Humans
  • Methylmalonyl-CoA Decarboxylase / chemistry
  • Methylmalonyl-CoA Decarboxylase / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Pyruvate Carboxylase / chemistry
  • Pyruvate Carboxylase / metabolism*


  • Biotin
  • Fatty Acid Synthase, Type II
  • Carbon-Nitrogen Ligases
  • biotin carboxylase
  • urea carboxylase (hydrolyzing)
  • Carbon-Carbon Ligases
  • Pyruvate Carboxylase
  • Acetyl-CoA Carboxylase
  • biotin carboxyl carrier protein
  • methylcrotonoyl-CoA carboxylase
  • geranoyl-CoA carboxylase
  • Methylmalonyl-CoA Decarboxylase