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Anaplerotic roles of pyruvate carboxylase in mammalian tissues - Cellular and Molecular Life Sciences

  • ️Wallace, J. C.
  • ️Tue Feb 28 2006

Abstract.

Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. PC serves an anaplerotic role for the tricarboxylic acid cycle, when intermediates are removed for different biosynthetic purposes. In liver and kidney, PC provides oxaloacetate for gluconeogenesis. In adipocytes PC is involved in de novo fatty acid synthesis and glyceroneogenesis, and is regulated by the peroxisome proliferator-activated receptor-γ, suggesting that PC is involved in the metabolic switch controlling fuel partitioning toward lipogenesis. In islets, PC is necessary for glucose-induced insulin secretion by providing oxaloacetate to form malate that participates in the ‘pyruvate/malate cycle’ to shuttle 3C or 4C between mitochondria and cytoplasm. Hyperglycemia and hyperlipidemia impair this cycle and affect glucose-stimulated insulin release. In astrocytes, PC is important for de novo synthesis of glutamate, an important excitatory neurotransmitter supplied to neurons. Transcriptional studies of the PC gene pinpoint some transcription factors that determine tissue-specific expression.

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Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, 10400, Thailand

    S. Jitrapakdee

  2. Department of Clinical Biochemistry, University of Cambridge, Cambridge, CB2 2QR, United Kingdom

    A. Vidal-Puig

  3. School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA5005, Australia

    J. C. Wallace

Authors

  1. S. Jitrapakdee

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  2. A. Vidal-Puig

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  3. J. C. Wallace

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Corresponding author

Correspondence to S. Jitrapakdee.

Additional information

Received 7 September 2005; received after revision 28 October 2005; accepted 8 December 2005

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Jitrapakdee, S., Vidal-Puig, A. & Wallace, J.C. Anaplerotic roles of pyruvate carboxylase in mammalian tissues. Cell. Mol. Life Sci. 63, 843–854 (2006). https://doi.org/10.1007/s00018-005-5410-y

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  • Published: 28 February 2006

  • Issue Date: April 2006

  • DOI: https://doi.org/10.1007/s00018-005-5410-y

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