The Behavior of Glutamate in the Gastrointestinal Tract

Glutamate, besides imparting the umami taste to foods, can act as a precursor for important bioactive molecules involved in various fundamental metabolic processes such as glutathione, proline, and arginine.

Scientists have investigated whether the high rate of intestinal metabolism and consequent energy generation can occur from both dietary glutamate and endogenous (internally produced) glutamate. Evidence so far indicates that dietary glutamate is metabolized more efficiently than endogenous glutamate—even when provided in large quantities—and that its oxidation into carbon dioxide is a major route for energy production.

This underscores the importance of including glutamate-rich foods in the daily diet (Burrin & Stoll, 2009; Burrin, 2000).

The intestinal metabolism of dietary glutamate occurs in enterocytes, the epithelial cells lining the intestinal mucosa. The process begins with glutamate molecules moving from the intestinal lumen into enterocytes via the apical membrane through the X-AG amino acid transport system. This system comprises a family of transporters with high affinity for glutamate, including GLAST-1 (glutamate-aspartate transporter 1), GLT-1 (glutamate transporter), and EAAC-1 (excitatory amino acid carrier)—the latter being the most abundant in the intestine. These transporters transfer glutamate from the intestinal lumen into enterocytes (Burrin & Stoll, 2009).

Once inside the enterocyte, nearly all dietary glutamate (about 80–95%) is catabolized via transamination by enzymes such as aspartate aminotransferase, alanine aminotransferase, branched-chain aminotransferase, and glutamate dehydrogenase (GDH). These enzymes remove the amino group from glutamate, transferring it to α-ketoglutarate.

This reaction also yields an α-keto acid (e.g., oxaloacetate), which enters the Krebs cycle and is ultimately oxidized to CO₂ and H₂O, generating ATP (the primary energy molecule for cells).

Approximately 95% of dietary glutamate is metabolized by the intestinal mucosa. Of this amount, about 50% is converted to CO₂, whereas dietary glucose undergoes minimal oxidation. Glutamine contributes no more than 15% to CO₂ production. This underscores glutamate’s superiority over other energy substrates for supporting intestinal energy production (Tomé, 2018).

Moreover, glutamate plays a significant role in the biosynthesis of two amino acids—arginine and proline—that are involved in reproductive capacity, immune, gastrointestinal, hepatic, cardiovascular, and pulmonary functions, as well as collagen synthesis.

Glutamate also serves as a precursor for the synthesis of 2-oxoglutarate, L-alanine, ornithine, glutathione, and γ-aminobutyric acid (GABA), all essential for protecting the intestinal mucosa and performing various other physiological functions (Burrin & Stoll, 2009; Burrin, 2000; Tomé, 2018).

In conclusion, dietary glutamate is indispensable for optimal intestinal function and maintenance of the intestinal mucosa.