anaplerotic

Anaplerotic refers to metabolic processes that replenish the intermediates of the tricarboxylic acid (TCA) cycle, which can be depleted when these intermediates are diverted for biosynthesis or energy production. The term is used to describe reactions that restore the pool of TCA cycle intermediates, ensuring continued operation of the cycle and continued supply of carbon skeletons for essential biosynthetic pathways.

The primary anaplerotic routes involve carbon entry into the TCA cycle from different substrates. The best known is the conversion of pyruvate to oxaloacetate by pyruvate carboxylase, a mitochondrial enzyme that uses CO2 and ATP to replenish oxaloacetate directly. Propionyl-CoA carboxylase supplies succinyl-CoA from propionyl-CoA, accommodating metabolism of odd-chain fatty acids and certain amino acids. Glutamine, via glutaminolysis, is a major anaplerotic source in many cells, converting to glutamate and then to α-ketoglutarate, which feeds the cycle; other amino acids can contribute to oxaloacetate, malate, fumarate, or α-ketoglutarate through transamination and deamination reactions.

Anaplerosis is contrasted with cataplerosis, the removal of TCA intermediates for biosynthetic purposes such as fatty acid synthesis or gluconeogenesis. The balance between anaplerotic input and cataplerotic output influences cellular metabolism, energy production, and the generation of biosynthetic precursors. In rapidly proliferating cells and certain physiological states, anaplerotic flux is particularly important for sustaining the TCA cycle and metabolic flexibility.