Pyruvate Carboxylase Function in Cancer Metabolism
Summary
Pyruvate carboxylase (PC) is a mitochondrial biotin-dependent enzyme that catalyses the ATP-dependent carboxylation of pyruvate to oxaloacetate, thereby replenishing tricarboxylic acid (TCA) cycle intermediates and supporting anaplerotic flux. In cancer cells, PC underpins metabolic plasticity by linking glycolysis, glutaminolysis and lipid synthesis to energy production and redox homeostasis. Elevated PC activity enables tumour cells to adapt to fluctuating nutrient and oxygen supplies, driving proliferation, survival under oxidative stress and metastatic competence. Beyond bioenergetics, PC-derived oxaloacetate contributes to biosynthetic pathways for amino acids, nucleotides and fatty acids, while modulating the balance between oxidative phosphorylation and lactate production. The dual role of PC in sustaining anabolic growth and regulating the tumour microenvironment—particularly immune cell function—positions it as a central metabolic nexus with global significance for therapeutic intervention.
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Pyruvate Carboxylase Function in Cancer Metabolism publication trend
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Technical terms
Anaplerosis: The process of replenishing TCA cycle intermediates to sustain continuous cycle function and biosynthesis in cells.
Tricarboxylic acid (TCA) cycle: A central mitochondrial pathway that oxidises acetyl-CoA to generate reducing equivalents for ATP production and provides precursors for biosynthesis.
Oxaloacetate: A four-carbon TCA cycle intermediate produced by PC that serves as a substrate for citrate synthesis and gluconeogenesis.
Gluconeogenesis: The metabolic pathway that generates glucose from non-carbohydrate precursors, requiring PC activity for pyruvate conversion in mitochondria.
Oxidative phosphorylation: The mitochondrial process by which electrons from reducing equivalents drive ATP synthesis, balancing cellular redox status.
References
- Hypoxia-mediated repression of pyruvate carboxylase drives immunosuppression. Breast Cancer Research (2024).
- Pyruvate carboxylase and cancer progression. Cancer & Metabolism (2021).
- Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer. Breast Cancer Research (2018).
- Targeting Pyruvate Carboxylase by a Small Molecule Suppresses Breast Cancer Progression. Advanced Science (2020).
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