Review

Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 7, pp 843-854

First online:

Anaplerotic roles of pyruvate carboxylase in mammalian tissues

  • S. JitrapakdeeAffiliated withDepartment of Biochemistry, Faculty of Science, Mahidol University Email author 
  • , A. Vidal-PuigAffiliated withDepartment of Clinical Biochemistry, University of Cambridge
  • , J. C. WallaceAffiliated withSchool of Molecular and Biomedical Science, University of Adelaide

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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.

Keywords.

Pyruvate carboxylase biotin carboxylase glucose-induced insulin secretion pyruvate/malate shuttle pyruvate/citrate shuttle type 2 diabetes lipogenesis glyceroneogenesis astrocytes glutamate synthesis