Anaplerosis for Glutamate Synthesis in the Neonate and in Adulthood

Abstract

A central task of the tricarboxylic acid (TCA, Krebs, citric acid) cycle in brain is to provide precursors for biosynthesis of glutamate, GABA, aspartate and glutamine. Three of these amino acids are the partners in the intricate interaction between astrocytes and neurons and form the so-called glutamine–glutamate (GABA) cycle. The ketoacids α-ketoglutarate and oxaloacetate are removed from the cycle for this process. When something is removed from the TCA cycle it must be replaced to permit the continued function of this essential pathway, a process termed anaplerosis. This anaplerotic process in the brain is mainly carried out by pyruvate carboxylation performed by pyruvate carboxylase. The present book chapter gives an introduction and overview into this carboxylation and additionally anaplerosis mediated by propionyl-CoA carboxylase under physiological conditions in the adult and in the developing rodent brain. Furthermore, examples are given about pathological conditions in which anaplerosis is disturbed.