Figure 7.

Glutamate oxidation via the TCA cycle coupled to the urea cycle after TBI

This schematic illustrates how glutamate can be used as an alternative fuel source when pyruvate carbons are prevented from entering the TCA cycle (bold arrows). The blue shaded metabolites represent the metabolites participating in glutamate metabolism. Bolded metabolites represent molecules measured in this study. Pyruvate and lactate metabolites are shaded in purple to illustrate that glycolysis and the TCA cycle are decoupled from one another, following acute TBI. Select enzymes discussed are italicized. TBI is known to damage and impair pyruvate dehydrogenase and coenzyme A (CoASH). This pathway bypasses the need for the first several steps of the TCA cycle that couple glucose metabolism to the TCA cycle and are blocked in the context of TBI. The TCA cycle continues on to generate high energy intermediates (red and dark purple) that facilitate oxidative phosphorylation. This pathway ultimately produces citrulline, nitric oxide (NO) by nitric oxide synthases and urea via the arginine to ornithine branch. This figure was created with BioRender.com.