Glutamate metabolism in a human intestinal epithelial cell layer model
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ORIGINAL ARTICLE
Glutamate metabolism in a human intestinal epithelial cell layer model Ryosei Sakai1 · Yuri Ooba1 · Akiko Watanabe1 · Hidehiro Nakamura1 · Yasuko Kawamata1 · Tomoko Shimada1 · Asuka Takumi1 · Johannes B. van Goudoever2 · Takahiro Narita1 Received: 27 April 2020 / Accepted: 30 October 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Plasma glutamate concentrations are constant despite dynamic changes in diets. Most likely, virtually all the dietary glutamate is metabolized in the gut. The present study investigated permeability and metabolism of dietary glutamate in a Caco-2 intestinal epithelial cell layer model by tracing the fate of [U-13C] or [15N]glutamate added to the apical medium. For comparison, several other labelled essential and non-essential amino acids were tested as well. Almost all the labelled glutamate in the apical medium (98% and 96% at 24 h of the culture, respectively) was incorporated in the cell layer, while it barely appeared at the basolateral side, indicating an almost complete utilization of glutamate. Indeed, the 13C was incorporated into alanine, proline, ornithine, and glutamine, and the 15N was incorporated into alanine, glutamine, ornithine, proline, branched chain amino acids and also found as ammonia indicative of oxidation. In contrast, substantial apical-to-basolateral transport of amino acids (8–85% of uptake) other than glutamate and aspartate was evident in studies using amino acid tracers labelled with 13C, 15N or D. These results suggest that the intestinal epithelial cell monolayer utilizes dietary glutamate which adds to maintaining glutamate homeostasis in the body. Keywords Metabolic barrier · Intestinal mucosa · Stable isotope · Amino acid · Glutamic acid
Introduction Glutamate, a nonessential amino acid, not only is a building block of proteins but has also a variety of other roles in the body. Since its amino moiety is readily exchanged with other amino acids by the corresponding aminotransferase, glutamate metabolism is linked to both the catabolism and anabolism of other amino acids (Sakai et al. 2004). Since deamination of glutamate generates α-ketoglutarate, a TCA cycle metabolite, this process is an important anaplerotic pathway. In addition, exchange of the amino moieties of Handling editor: G. Wu. * Ryosei Sakai [email protected] 1
Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc, 1‑1 Suzuki‑cho, Kawasaki 210‑8681, Japan
Department of Pediatrics, Amsterdam UMC Vrije Universiteit, University of Amsterdam, Emma Children’s Hospital, Amsterdam, The Netherlands
2
glutamate and aspartate is an essential component of the malate-aspartate shuttle, which transfers NADH across mitochondrial membranes. Extracellular glutamate also has unique functions. Recently, it was suggested that glutamate is a signalling molecule also in nonneuronal tissues, since glutamate receptors are expressed in various types of cells (Du et al. 2016). To fulfil the function of glutamate as a signalling
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