Physiological Functions of Glutamate During Pregnancy

Glutamate is one of the most abundant amino acids in nature. It naturally occurs in foods and its primary functions include stimulating the umami taste on the tongue, enhancing protein digestion in the stomach, and providing energy to the intestine.

Beyond its role in foods, glutamate is an important non-essential amino acid—meaning it’s synthesized within the body. Its functions begin as early as fetal development, along with glutamine, another non-essential (or conditionally essential) amino acid produced from glutamate and ammonia.

Although still under investigation, the metabolism and transport of glutamate and glutamine exhibit unique characteristics that highlight the importance of interaction and communication between the placenta and fetal liver. These mechanisms help regulate the supply and concentrations of glutamate/glutamine available to the fetus.

It is known that the fetal liver is the primary producer of glutamate, although the placenta can also directly utilize glutamate from the maternal circulation. Meanwhile, the placenta transports glutamine—produced by itself or derived from the maternal blood—to the fetal circulation, and also captures glutamate produced by the fetal liver. This “exchange” defines the placental–fetal glutamine–glutamate cycle, which is essential for the healthy development of both the placenta and the fetus (Battaglia, 2000).

In this cycle, the placenta initially synthesizes glutamine and absorbs it from the maternal circulation. This glutamine enters the fetal circulation (via umbilical absorption) and is taken up by the fetal liver, where approximately 45 % of its carbons are used to produce glutamate. The newly synthesized glutamate is then released back into the fetal circulation and absorbed by the placenta. Only about 6 % of the carbons from the glutamate captured by the placenta are converted back into glutamine; the remaining carbons are converted into CO₂ (Vaughn et al., 1995; Ortiz et al., 2013).

Additionally, in the placenta, a high activity of branched-chain amino acid transaminases contributes to glutamate production via the formation of its ketoacid, α-ketoglutarate. Therefore, the placenta obtains glutamate both by reabsorption from the fetal circulation and by its own production, mediated by branched-chain amino acid transamination (e.g., from leucine).

The glutamate transporters EAAT1, EAAT2, EAAT3, EAAT4, and EAAT5 (Excitatory Amino Acid Transporters 1–5) are key components of the glutamate–glutamine cycle and are responsible for the active transport of glutamate across cell membranes.

Similar to its role in the intestine, much of the glutamate in the placenta is used as metabolic fuel and as a substrate to generate NADPH (the electron-accepting coenzyme) for the synthesis of fatty acids and steroids—thus conserving glucose for fetal use.

In essence, glutamate released from the fetal liver partially replaces hepatic glucose production as a primary energy source for the fetus. Therefore, the significance of both glutamate and glutamine is evident in ensuring fetal development, not only in terms of energy for various metabolic processes but also for the synthesis of essential substances like proteins and steroids and for maintaining protective systems within the organism.