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Anaplerotic roles of pyruvate carboxylase in mammalian tissues
Open accessAbstract
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-gamma, 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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“This PC-mediated alternative anaplerosis is considered important in specific types of cancers, including liver cancers and glioblastoma, for maintaining biosynthesis and redox homeostasis154–156.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [154]
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Metadata
- Authors
- Jitrapakdee, S., Vidal-Puig, A., & Wallace, J. C.
- Affiliations
- Mahidol University (TH)
- The University of Adelaide (AU)
- Corresponding author
- Jitrapakdee, S.
- ORCID
- Jitrapakdee, S.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2006-02-28
- Volume
- 63
- Issue
- 7-8
- Pages
- 843-854
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11136034
- OpenAlex
- W1986860566
- Cited by
- 149
- References
- 97
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 2 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 9 · 2017: 3 · 2016: 7 · 2015: 10 · 2014: 12 · 2013: 12 · 2012: 12
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- pyruvate carboxylase, anaplerosis, TCA cycle, oxaloacetate, gluconeogenesis, fatty acid synthesis, glyceroneogenesis, PPARγ, metabolic switch, lipogenesis, glucose-stimulated insulin secretion, malate, islets, astrocytes, glutamate synthesis, hyperglycemia, hyperlipidemia, tissue-specific gene expression, transcription factors
- MeSH terms
- Animals, Humans, Kidney, Liver, Pancreas, Pyruvate Carboxylase, Signal Transduction, Pyruvic Acid, Oxaloacetic Acid
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