Computational model of ketone metabolism matches MRS data and links ketones to lower brain glutamate and GABA

A computational model of brain ketone metabolism matched MRS data and suggests ketones reduce glutamate and GABA mainly by partially displacing glucose metabolism through the pseudo-malate-aspartate shuttle, with key enzymes selectively modulating each neurotransmitter.

• Design: a computational model of neurotransmitter cycling centered on the pseudo-malate-aspartate shuttle was compared with MRS data from ketone administration experiments.
• Metabolic control analysis identified partial displacement of glucose metabolism through the pseudo-malate-aspartate shuttle as the dominant mechanism for observed reductions in glutamate and GABA.
• The authors present the model as a framework for hypothesis testing and treatment optimization relevant to researchers and clinicians.

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