Given the localization of enzymes, for each cycle citrulline must leave the mitochondria, and ornithine must enter the mitochondrial matrix. Carrier proteins in the inner mitochondrial membrane facilitate the necessary transmembrane fluxes or citrulline and ornithine. Krebs Cycle enzymes participate in regeneration of aspartate from fumarate, as shown on p. 621. Oxaloacetate is converted to aspartate via transamination, e.g., from glutamate. Total lack of any Urea Cycle enzyme is lethal.
Elevated ammonia is very toxic, particularly to the brain.
If not treated immediately after birth, severe mental retardation results. This would deplete glutamate, a neurotransmitter and the precursor for synthesis of GABA, another neurotransmitter. Depletion of glutamate, as well as the high ammonia level, would drive the Glutamate Dehydrogenase reaction to reverse . Liver transplantation has also been used, since liver is the organ that carries out Urea Cycle. Copyright 1998-2000 by Joyce J. Diwan.