Figure 6. An “oxaloacetate switch”.

(a) Proposed mechanism of regulating the TCA cycle in facultative anaerobes, such as E. coli. Under aerobic conditions (black arrows) pyruvate is metabolised via PDH, citrate synthase (CS), aconitase (Ac), isocitrate dehydrogenase (IDH), OGDH, succinyl-CoA synthetase (SS), succinate dehydrogenase (SDH), fumarase (Fu) and malate dehydrogenase (MDH). In the presence of high concentration of glucose (or other glycolytic substrates), the concentration of oxaloacetate is raised,⁵² and MDH, Fu, SDH and SS function in reverse, allowing anaerobic fermentation (red arrows). It is likely this pathway is aided by oxaloacetate-dependent inhibition of E1o. (b) Proposed regulation of 2-oxoglutarate (OG) flux by the oxaloacetate (green outline) in the mammalian brain. When oxaloacetate is in excess, OGDH is inhibited, allowing diversion of OG to generate the excitatory neurotransmitter, glutamate (magenta outline). Transamination between glutamate-oxaloacetate/aspartate-2-oxoglutarate is catalysed by amino acid aminotransferase. Isotope labelling studies suggest the amine for this product may be donated by aspartate (yellow outline) to leucine (to produce a substrate for the BCDH).⁴⁴