Skeletal muscle glutamate metabolism in health and disease: state of the art

Purpose of review Glutamate is an amino acid of interest because it participates in many metabolic pathways. However, there is evidence that skeletal muscle glutamate metabolism is disturbed in disease. This review presents current knowledge regarding the metabolic function and regulation of glutamate in skeletal muscle under physiological and pathophysiological circumstances. Furthermore, several options for modulating muscle glutamate concentration in order to improve glutamate metabolism are discussed. Recent findings The high correlation between muscle glutamate concentration and muscle glutathione concentration suggests that glutamate plays a determining role in the glutathione synthesis pathway. During exercise, glutamate plays a central role in energy provision because it participates in the tricarboxylic acid and the purine nucleotide cycles. However, a consistent finding in several diseases is reduced skeletal muscle glutamate. Remarkably, only few studies focused on modulation of muscle glutamate status either by exercise or by nutritional supplementation. There are several options for modulating glutamate metabolism, but the specific effects of the individual options require further elucidation. Nutritional supplementation of glutamate or its precursors glutamine, (ornithine) alpha-ketoglutarate, or the branched chain amino acids can influence muscle glutamate status. Summary Specific intervention studies must be conducted to investigate the effect of supplementation on skeletal muscle glutamate turnover and its related metabolic and functional consequences in healthy individuals and in patients with acute or chronic disease.