Orchestrating Physiological Homeostasis: The Spatial and Cellular Heterogeneity of Tryptophan Transport and Metabolism.
- 1Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China.
- 2Yuelushan Laboratory, Changsha, Hunan, 410128, China.
- 3Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China.
Abstract
In addition to being incorporated into proteins, tryptophan (Trp) is increasingly recognized as a critical metabolic hub orchestrating systemic physiological homeostasis through interactions among the digestive, nervous and immune systems. This review systematically delineates the latest advancements in the molecular mechanisms governing the spatial and cellular heterogeneity of Trp transport. We summarize the sophisticated transmembrane machinery of Trp transport in intestinal epithelial cells, including angiotensin-converting enzyme 2-dependent broad neutral amino acid transporter 1 complex in absorptive enterocytes and L-type amino acid transporter 1/alanine, serine, cysteine transporter 2-mediated uptake in secretory enterochromaffin cells. Additionally, the albumin-binding dynamics of Trp in tryptophan 2,3-dioxygenase-mediated hepatic first-pass gating and its metabolic shunting to peripheral tissues are also discussed in this review. By bridging micro-level transport mechanisms with macro-level physiological regulation, this review provides a comprehensive framework for understanding the pleiotropic functions of Trp and identifies transporter-enzyme coupling as a potential target for therapeutic intervention in metabolic disorders, neurodegenerative diseases, and immune dysfunction.
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BibTeX
@article{zhu2026orchestrating,
title = {{Orchestrating Physiological Homeostasis: The Spatial and Cellular Heterogeneity of Tryptophan Transport and Metabolism.}},
author = {Xiaofeng Zhu and Yuling Zhang and Songlin Zhang and Sitong Chen and Yulong Yin and Xiongzhuo Tang},
journal = {International journal of biological sciences},
year = {2026},
month = oct,
doi = {10.7150/ijbs.139760},
url = {https://europepmc.org/article/MED/42910287},
note = {CC BY},
}
RIS
TY - JOUR
TI - Orchestrating Physiological Homeostasis: The Spatial and Cellular Heterogeneity of Tryptophan Transport and Metabolism.
AU - Xiaofeng Zhu
AU - Yuling Zhang
AU - Songlin Zhang
AU - Sitong Chen
AU - Yulong Yin
AU - Xiongzhuo Tang
PY - 2026
DA - 2026/10/02
JO - International journal of biological sciences
DO - 10.7150/ijbs.139760
UR - https://europepmc.org/article/MED/42910287
AB - In addition to being incorporated into proteins, tryptophan (Trp) is increasingly recognized as a critical metabolic hub orchestrating systemic physiological homeostasis through interactions among the digestive, nervous and immune systems. This review systematically delineates the latest advancements in the molecular mechanisms governing the spatial and cellular heterogeneity of Trp transport. We summarize the sophisticated transmembrane machinery of Trp transport in intestinal epithelial cells, including angiotensin-converting enzyme 2-dependent broad neutral amino acid transporter 1 complex in absorptive enterocytes and L-type amino acid transporter 1/alanine, serine, cysteine transporter 2-mediated uptake in secretory enterochromaffin cells. Additionally, the albumin-binding dynamics of Trp in tryptophan 2,3-dioxygenase-mediated hepatic first-pass gating and its metabolic shunting to peripheral tissues are also discussed in this review. By bridging micro-level transport mechanisms with macro-level physiological regulation, this review provides a comprehensive framework for understanding the pleiotropic functions of Trp and identifies transporter-enzyme coupling as a potential target for therapeutic intervention in metabolic disorders, neurodegenerative diseases, and immune dysfunction.
SN - 1449-2288
ER -