The Key Role of Anaplerosis and Cataplerosis for Citric Acid Cycle Function*

By O. E. Owen, S. Kalhan, R. Hanson. Journal of Biological Chemistry, 2002

1,081 citations recorded by the source corpus.

cycle is thecentral process in energy metabolism. However, the TCA cyclealso functions in biosynthetic pathways in which intermediatesleave the cycle to be converted primarily to glucose, fatty acids,or non-essential amino acids. If TCA cycle anions are removedfrom the cycle they must be replaced to permit its continuedfunction. This process is termed

Subfields: Clinical Biochemistry, Molecular Biology, Physiology

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In Clinical Biochemistry

1. C. V. Dang
2. Eyal Gottlieb
3. P. Crawford
4. Erika L. Pearce
5. M. V. Vander Heiden
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7. Patrycja Puchalska

In Molecular Biology

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2. M. V. Vander Heiden
3. Navdeep S. Chandel
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In Physiology

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2. N. Hay
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4. P. Crawford
5. Erika L. Pearce
6. M. V. Vander Heiden
7. Sophia Y. Lunt
8. Patrycja Puchalska

Citations in the corpus

• N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. (2007, background): “Two important cataplerotic enzymes that help remove excess TCA intermediates are aspartate aminotransferase and citrate lyase (Owen et al., 2002).”
• Fundamentals of cancer metabolism (2016, background): “Their utilization in biosynthetic pathways requires that carbon be resupplied to the cycle so that intermediate pools aremaintained; pathways that “refill” the cycle are termed anaplerotic pathways, and they generate TCA cycle intermediates that can enter the cycle at sites other than acetyl-CoA (co”
• Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer (2006, background): “Moreover, enhanced glucose breakdown provides building blocks for the synthesis of nucleotides (via the pentose phosphate pathway), and amino and fatty acids (from glycolytic and TCA cycle intermediates) (Figure 1) (Owen et al., 2002).”
• Links between metabolism and cancer. (2012, positive): “Glutamine released into the circulation is used by the kidney for gluconeogenesis by conversion to glutamate and then to aKG, which ends up as oxaloacetate and phosphoenol pyruvate for glucose synthesis (Owen et al. 2002).”
• Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “Amino acids enter the TCA cycle via pyruvate, acetyl-CoA, acetoacetylCoA, α-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate (Owen et al 2002, Voet & Voet 2004).”
• Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics (2017, background): “Acetyl-CoA allosterically activates (1) pyruvate carboxylase (PC), thereby activating a metabolic control mechanism that augments anaplerotic entry of metabolites into the TCA cycle (Owen et al., 2002; Scrutton and Utter, 1967), and (2) pyruvate dehydrogenase kinase, which phosphorylates and inhibit”
• Regulation of pyruvate metabolism and human disease (2013, background): “For example, α-ketoglutarate is a key intermediate for the biogenesis of glutamine, glutamate, arginine, and proline, while oxaloacetate is used to generate aspartate and asparagine [119].”
• An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma (2016, positive): “We next investigated the TCA cycle, which plays central roles in both ATP production through oxidation of acetyl-CoA to CO2 and the production of biosynthetic precursors (Owen et al., 2002).”
• Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport (2014, background): “These OAA-producing pathways, termed anaplerosis, enable the TCA cycle to function as a biosynthetic pathway as opposed to a purely bioenergetic one (Owen et al., 2002).”
• Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer (2013, background): “Corresponding reductions in citrate abundance, derived from Glc, and TCA cycle intermediates, derived from Gln, could be both a cause and a consequence of reduced Gln incorporation, as anaplerosis and cataplerosis are always tightly matched to maintain TCA cycle carbon balance (Owen et al., 2002).”
• Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans (2011, neutral): “When tricarboxylic acid cycle intermediates are withdrawn for biosynthesis, they are replenished by converting PEP and pyruvate directly to OAA (12).”
• The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. (2015, background): “Glucose-derived pyruvate is an important source of acetylCoA, which is a key carbon input into the TCA cycle (Owen et al., 2002).”