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Cellular and Molecular Life Sciences

, Volume 70, Issue 5, pp 863–891 | Cite as

Structure and function of biotin-dependent carboxylases

  • Liang TongEmail author
Review

Abstract

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.

Keywords

Fatty acid metabolism Carbohydrate metabolism Amino acid metabolism Metabolic syndrome Obesity Diabetes Cancer Drug discovery Antibiotics Propionic acidemia 3-methylcrotonylglycinuria Lactic acidemia 

Abbreviations

ACC

Acetyl-CoA carboxylase

BC

Biotin carboxylase

BCCP

Biotin carboxyl carrier protein

BT

BC-CT interaction

CT

Carboxyltransferase

GCC

Geranyl-CoA carboxylase

GCD

Glutaconyl-CoA decarboxylase

HCS

Holocarboxylase synthase

MCC

3-methylcrotonyl-CoA carboxylase

MCG

3-methylcrotonylglycinuria

PA

Propionic acidemia

PC

Pyruvate carboxylase

PCC

Propionyl-CoA carboxylase

PT

PC tetramerization

UA

Urea amidolyase

UC

Urea carboxylase

YCC

Acyl-CoA carboxylase (generic name)

Notes

Acknowledgments

I thank Matthew Callaghan, Chi-Yuan Chou, Daniel Floyd, Christine Huang, Yi Seul Kim, Jiang Li, Svetlana Novoseletskaya, Kianoush Sadre-Bazzaz, Yang Shen, Timothy Tran, Benjamin Tweel, Jia Wei, Song Xiang, Zhiru Yang, Linda Yu, and Hailong Zhang for contributions to this project and for helpful discussions. I apologize for not being able to cite many of the earlier publications due to space limitations. This research was supported in part by a grant from the NIH to LT (DK067238).

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© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Department of Biological SciencesColumbia UniversityNew YorkUSA

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