Therapies manipulating interorgan ammonia and amino acid metabolism. In liver failure, the relative activities of cellular glutamine syntheses (GS) and phosphate-activated glutaminase (PAG) in different organs influence interorgan ammonia and amino acid metabolism. With a loss of hepatic urea cycle capacity, hyperammonaemia is predominately due to worsening intestinal and renal ammonia efflux, with skeletal muscle having the potential to increase its ability to detoxify ammonia. Though the brain also detoxifies ammonia, this is counterproductive as resultant astrocyte glutamine accumulation induces brain swelling. This schematic highlights not only current standard therapies for hyperammonaemia which principally act on individual organs (e.g., purgatives targeting intestinal ammonia production), but also newer interventions targeting multiple organs (e.g., LOLA and OP).
