Abstract
In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti carried out a mathematical analysis of neurotransmitter pathways in brain, modeling compartmental nitrogen flux among several major participants – ammonia, glutamine, glutamate, GABA, and selected amino acids. This analysis is important because cerebral nitrogen metabolism is perturbed in many diseases, including liver disease and inborn errors of the urea cycle. These diseases result in an elevation of blood ammonia, which is neurotoxic. Here, a brief description is provided of the discovery of cerebral metabolic compartmentation of nitrogen metabolism – a key feature of cerebral glutamate–glutamine and GABA–glutamine cycles. The work of Somersalo and Calvetti is discussed as a model for future studies of normal and pathological cerebral ammonia metabolism.
Highlights
In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti carried out a mathematical analysis of neurotransmitter pathways in brain, modeling compartmental nitrogen flux among several major participants – ammonia, glutamine, glutamate, GABA, and selected amino acids.This analysis is important because cerebral nitrogen metabolism is perturbed in many diseases, including liver disease and inborn errors of the urea cycle
Glutamate released during neurotransmission is taken up in the small compartment, where it is converted to glutamine by Glutamine synthetase (GS)
Glutamine is released from the astrocytes to the large compartment where it is hydrolyzed by glutaminase to glutamate and ammonia, completing the cycle [7, 8]
Summary
In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti carried out a mathematical analysis of neurotransmitter pathways in brain, modeling compartmental nitrogen flux among several major participants – ammonia, glutamine, glutamate, GABA, and selected amino acids.This analysis is important because cerebral nitrogen metabolism is perturbed in many diseases, including liver disease and inborn errors of the urea cycle. As pointed out by Somersalo and Calvetti [42] the proposed BCAA/BCKA shuttle is problematic because the GDH reaction is suggested to proceed in the direction of reductive amination of α-ketoglutarate in the neurons and oxidation of glutamate in the astrocytes.
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