Aminotransferases.

The aminotransferases are PLP-dependent proteins which catalyse the transfer of an amino group from the donor amino acid to α-ketoglutarate, forming glutamate and the respective keto acids. Several key aminotransferase proteins have been identified as playing central roles in whole-body nitrogen metabolism, where they share common functions as nitrogen donors. These pathways play integrated roles within cells and between tissues, shuttling metabolites alluding to distinct pockets of compartmented metabolic activity. These anaplerotic shuttles interface with key metabolic pathways, for example the glutamate/glutamine cycle and TCA cycle, facilitating the regeneration of key metabolites such as the primary neurotransmitter glutamate. Contributions to glutamate levels in the brain from these anaplerotic pathways exceed 30%, illustrating their importance in maintaining the neurotransmitter pool of glutamate in neuronal cells. Knowledge of these pathways is not only important to our understanding of normal physiological mechanisms, but even more to the ways in which they alter and contribute to the pathogenesis of disease. The pathological implications of impaired aminotransferase metabolism is discussed, in particular their potential role in glutamate toxicity, which has been implicated in the pathogenesis of neurodegenerative disease. Finally, because of their tissue distribution these proteins have additional roles as biomarkers of disease, and can be used in the differential diagnosis of acute and chronic hepatic injury.