The importance of glutamate in hepatic metabolic processes

Glutamate, naturally present in foods or in the form of monosodium glutamate, is one of the main elements that impart umami taste. When ingested, it can be extensively metabolized in the intestine. What is not utilized by this organ (approximately 5%) reaches the liver through the portal circulation, where it participates in various reactions, which will be described below.

Glutamate, synthesized by the body to perform fundamental functions in various organs, including the liver, can play a central role in amino acid metabolism, both in their synthesis and degradation. The main processes in which it participates are transamination and deamination reactions, the urea cycle, the Krebs cycle, and gluconeogenesis. Due to its numerous functions, glutamate is considered by some researchers to be “the central component of hepatic metabolism” (ORTIZ, 2013; ALBARRACÍN et al., 2016).

In transamination reactions, glutamate can act as an amine donor (NH2), like other amino acids (except threonine and lysine), and as an amine acceptor, since the main α-ketoacid required by aminotransferases to receive the amino group donated by amino acids is α-ketoglutarate, which, after the reaction, is transformed into glutamate (BROSNAN & BROSNAN, 2009).

Through the deamination reaction, glutamate releases the amino group in the form of an ammonium ion (toxic), which is converted into urea (non-toxic) and eliminated through urine, removing approximately 95% of this toxic ion derived from the catabolism of amino acids and proteins from the body (ORTIZ, 2013).

Therefore, depending on the amount of protein to which the body is exposed, the transamination and deamination reactions adjust to maintain balance and control the elimination of their products. Thus, in the case of a high-protein diet, which generates excess nitrogen, glutamate plays an important role by receiving the amino groups from the transamination of amino acids and then releasing them through deamination in the form of ammonium ions, which are then eliminated from the body through the urea cycle, in which glutamate also participates as a precursor of ornithine, arginine, and N-acetylglutamate, a molecule that activates carbamoylphosphate synthase 1, an enzyme essential for initiating the reactions in this cycle. Furthermore, glutamate is also a precursor of aspartate (through transamination with oxaloacetate), which donates the second nitrogen to urea (BROSNAN & BROSNAN, 2009).

Regarding the metabolism of the glutamate carbon skeleton, it is known that it donates energy in the Krebs cycle, as do the other amino acids of the “glutamate family”—glutamine, histidine, arginine, ornithine, and proline—which are also converted to α-ketoglutarate, an intermediate in the cycle. However, in fasting situations, the glutamate carbon skeleton can enter the gluconeogenesis pathway to control blood glucose homeostasis (ALBARRACÍN et al., 2016).

Given the involvement of glutamate in hepatic metabolism, it is important to emphasize that each of these reactions occurs in different zones or regions of the liver and is reversible, allowing for the adjustment and control of metabolic processes and the individual regulation of each mechanism, according to the body’s needs (BROSNAN & BROSNAN, 2009; ALBARRACÍN et al., 2016).

Therefore, it is possible to consider that glutamate metabolism is necessary both for energy support through the formation of α-ketoglutarate and its subsequent entry into the Krebs cycle, and for controlling the body’s safety through participation in the regulation of the urea cycle.