The metabolic pathways that replenish the TCA cycle hold the key to treating some of medicine's most devastating inherited metabolic disorders.
Read More →Anaplerosis—from the Greek ana (up) and plerotikos (to fill)—describes the biochemical reactions that replenish intermediates of the tricarboxylic acid (TCA) cycle. When these pathways fail due to inherited enzyme deficiencies, the consequences cascade through every energy-dependent tissue in the body: brain, heart, liver, and skeletal muscle.
The 2020 FDA approval of triheptanoin (Dojolvi®) for long-chain fatty acid oxidation disorders marked a watershed moment—the first therapy designed explicitly to exploit anaplerotic biochemistry. But this is just the beginning. Research into anaplerotic substrates, gene therapy for TCA cycle enzymes, and metabolic flux analysis is reshaping how we approach inborn errors of metabolism.
This resource explores the science, the therapies, and the clinical genetics behind anaplerotic medicine—authored by board-certified clinical geneticists who manage these conditions every day.
The metabolic process of replenishing TCA cycle intermediates, from Kornberg's 1966 coinage to modern therapy
How triheptanoin (Dojolvi) works — odd-chain triglyceride metabolism, propionyl-CoA, succinyl-CoA replenishment
Emerging applications: Huntington disease, GLUT1 deficiency, refractory epilepsy, cancer immunotherapy, stroke