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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

Highly-Time-Resolved Measurements of Tryptophan's Distribution and Homeostatic Regulation in Live, Intact Animals.

  • Yuyang Wu1
  • Chelsea N Brown2
  • Zeki Duman3
  • Rose Mery Bakestani1
  • Carl M Kirkpatrick4
  • Joao Hespanha3
  • Tod Kippin5,6,7
  • Kevin W Plaxco1,7
7 affiliations
  1. 1Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California, USA.
  2. 2Institute of Collaborative Biotechnology, University of California Santa Barbara, Santa Barbara, California, USA.
  3. 3Department of Electrical and Computer Engineering, University of California Santa Barbara, Santa Barbara, California, USA.
  4. 4Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
  5. 5Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, California, USA.
  6. 6Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California, USA.
  7. 7Biological Engineering Graduate Program, University of California Santa Barbara, Santa Barbara, California, USA.
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Abstract

Current theories regarding tryptophan's homeostatic regulation, which are derived from in vitro, post-mortem, and cell-culture studies, lack any direct evidence supporting their occurrence in living subjects. In response, here we have used 20 s resolution, multi-hour plasma measurements to confirm, for the first time, that the cooperativity and tryptophan-induced stabilization of tryptophan 2,3-dioxygenase (TDO) seen in vitro and in cell culture hold in live, intact animals. For example, a model coupling these regulatory mechanisms with a constant tryptophan production rate from tissue reservoirs describes our in vivo measurements quantitatively, and provides high-precision estimates of tryptophan flux and tryptophan-induced TDO up-regulation in individual subjects. In bridging a longstanding gap between ex vivo, post-mortem, and cell culture investigations and the physiology of live, intact animals, an advance that had previously only been reported for glucose, our results highlight the transformative power of applying only-recently-available, seconds-resolved metabolite measurements to the study of metabolic regulation.

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Cite

BibTeXRIS
BibTeX
@article{wu2026highlytimeresolved,
  title = {{Highly-Time-Resolved Measurements of Tryptophan's Distribution and Homeostatic Regulation in Live, Intact Animals.}},
  author = {Yuyang Wu and Chelsea N Brown and Zeki Duman and Rose Mery Bakestani and Carl M Kirkpatrick and Joao Hespanha and Tod Kippin and Kevin W Plaxco},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.77595},
  url = {https://europepmc.org/article/MED/42881339},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Highly-Time-Resolved Measurements of Tryptophan's Distribution and Homeostatic Regulation in Live, Intact Animals.
AU  - Yuyang Wu
AU  - Chelsea N Brown
AU  - Zeki Duman
AU  - Rose Mery Bakestani
AU  - Carl M Kirkpatrick
AU  - Joao Hespanha
AU  - Tod Kippin
AU  - Kevin W Plaxco
PY  - 2026
DA  - 2026/10/15
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.77595
UR  - https://europepmc.org/article/MED/42881339
AB  - Current theories regarding tryptophan's homeostatic regulation, which are derived from in vitro, post-mortem, and cell-culture studies, lack any direct evidence supporting their occurrence in living subjects. In response, here we have used 20 s resolution, multi-hour plasma measurements to confirm, for the first time, that the cooperativity and tryptophan-induced stabilization of tryptophan 2,3-dioxygenase (TDO) seen in vitro and in cell culture hold in live, intact animals. For example, a model coupling these regulatory mechanisms with a constant tryptophan production rate from tissue reservoirs describes our in vivo measurements quantitatively, and provides high-precision estimates of tryptophan flux and tryptophan-induced TDO up-regulation in individual subjects. In bridging a longstanding gap between ex vivo, post-mortem, and cell culture investigations and the physiology of live, intact animals, an advance that had previously only been reported for glucose, our results highlight the transformative power of applying only-recently-available, seconds-resolved metabolite measurements to the study of metabolic regulation.
SN  - 2198-3844
ER  -