ABSTRACT
Removal of excess ammonia in mammalian systems depends principally on its conversion to urea via the urea cycle, a metabolic pathway that is only expressed in the liver although other tissues, including the brain, may express some of its constituent enzymes. Glutamine (GLN), a nonessential amino acid, is found abundantly in the central nervous system where it participates in a variety of metabolic pathways. Its major role in the brain is that of precursor of the releasable pool of the excitatory neurotransmitter amino acid glutamate and the inhibitory amino acid, γ-amino butyric acid. Ammonia removal by the brain is an astrocytic responsibility since the enzyme responsible has a predominantly, and perhaps exclusively, astrocytic localization. An important but little-studied step in GLN metabolism involves GLN transamination resulting in the production of alpha-ketoglutaramate that may then be hydrolyzed to alpha-ketogluta-rate and ammonia in a reaction catalyzed by omega-amidase, the so-called glutaminase-II pathway.
