Key terms and definitions for Anaplerosis.
- Anaplerosis
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The enzymatic replenishment of TCA cycle intermediates that have been diverted to biosynthetic pathways. Essential for maintaining oxidative metabolism when intermediates are consumed for gluconeogenesis, amino acid synthesis, or heme production.
- Cataplerosis
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The removal of TCA cycle intermediates for use in biosynthetic reactions—the counterpart to anaplerosis. The balance between anaplerotic and cataplerotic flux determines the functional capacity of the TCA cycle.
- Tricarboxylic Acid (TCA) Cycle
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The central metabolic pathway occurring in the mitochondrial matrix that oxidizes acetyl-CoA to CO₂, generating NADH and FADH₂ for the electron transport chain. Also known as the Krebs cycle or citric acid cycle.
- Triheptanoin
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An odd-chain triglyceride (C7:0) FDA-approved as Dojolvi® for long-chain fatty acid oxidation disorders. Its metabolism produces both acetyl-CoA and propionyl-CoA, the latter providing anaplerotic substrate via succinyl-CoA.
- Oxaloacetate
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A four-carbon dicarboxylic acid that serves as both the starting and ending point of the TCA cycle. Its regeneration is rate-limiting and is the primary target of anaplerotic reactions via pyruvate carboxylase.
- α-Ketoglutarate
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A five-carbon TCA cycle intermediate that also serves as a key metabolic branchpoint, linking carbon and nitrogen metabolism through transamination reactions with amino acids.
- Pyruvate Carboxylase
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A biotin-dependent mitochondrial enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate—the most important anaplerotic reaction in most tissues. Deficiency causes severe lactic acidosis and neurological impairment.
- Long-Chain Fatty Acid Oxidation Disorder (LC-FAOD)
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A group of inherited metabolic diseases affecting mitochondrial β-oxidation of long-chain fatty acids (C14-C20). Includes VLCAD, LCHAD, TFP, and CPT II deficiencies. Triheptanoin provides anaplerotic therapy.
- Propionyl-CoA
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A three-carbon acyl-CoA produced from odd-chain fatty acid oxidation and branched-chain amino acid catabolism. Enters the TCA cycle via methylmalonyl-CoA and succinyl-CoA—a key anaplerotic pathway.
- Metabolic Flux
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The rate of metabolite flow through a metabolic pathway, measured in moles per unit time. Anaplerotic flux quantifies the rate at which TCA cycle intermediates are replenished.
- Succinyl-CoA
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A TCA cycle intermediate formed from α-ketoglutarate. Also an entry point for anaplerotic substrates derived from odd-chain fatty acids (via propionyl-CoA) and certain amino acids.
- Acetyl-CoA
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The two-carbon unit that enters the TCA cycle by condensing with oxaloacetate to form citrate. Unlike anaplerotic substrates, acetyl-CoA cannot replenish cycle intermediates—it can only be oxidized.
- Glutaminolysis
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The metabolic pathway by which glutamine is converted to glutamate and then to α-ketoglutarate, providing a major anaplerotic source in rapidly dividing cells and cancer metabolism.
- Biotin
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An essential B-vitamin (B7) that serves as a cofactor for carboxylase enzymes including pyruvate carboxylase and propionyl-CoA carboxylase—both critical for anaplerosis. Biotinidase deficiency impairs recycling.
- Malic Enzyme
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An enzyme that converts malate to pyruvate (cataplerotic) or, in the reverse direction, provides an alternative anaplerotic pathway from pyruvate to malate in some tissues.