Tph1, or tryptophan hydroxylase 1, is a rate-limiting enzyme in serotonin synthesis. Serotonin is an important neurotransmitter, growth factor and hormone mediating various physiological functions. Tph1 is mainly expressed by specialized gut endocrine enterochromaffin cells and some non-neuronal cell types like adipocytes [2]. It is involved in tryptophan metabolism, a pathway crucial for maintaining normal physiological states [1].

In a CUMS mouse model of depression, berberine improved depressive behaviors by activating Tph1, promoting tryptophan biotransformation into serotonin and inhibiting the kynurenine metabolism pathway, suggesting Tph1's role in mood-related regulation [1]. In bladder cancer, overexpression of Tph1 in T24 cells using experimental models led to declined cell survival, and Tph1-deficient cell lines showed increased clones, indicating Tph1 may inhibit bladder tumorigenesis via the HIF-1α pathway [3].

In conclusion, Tph1 plays essential roles in serotonin synthesis and tryptophan metabolism. Findings from animal models suggest its significance in mood-related disorders like depression and in cancer development, specifically bladder cancer. Understanding Tph1's functions can provide insights into the mechanisms of these diseases and potential therapeutic targets.

References:

1. Ge, Ping-Yuan, Qu, Shu-Yue, Ni, Sai-Jia, Zhang, Qi-Chun, Zhu, Hua-Xu. 2022. Berberine ameliorates depression-like behavior in CUMS mice by activating TPH1 and inhibiting IDO1-associated with tryptophan metabolism. In Phytotherapy research : PTR, 37, 342-357. doi:10.1002/ptr.7616. https://pubmed.ncbi.nlm.nih.gov/36089660/

2. Jones, Lauren A, Sun, Emily W, Martin, Alyce M, Keating, Damien J. 2020. The ever-changing roles of serotonin. In The international journal of biochemistry & cell biology, 125, 105776. doi:10.1016/j.biocel.2020.105776. https://pubmed.ncbi.nlm.nih.gov/32479926/

3. Ren, Jianwei, Mo, Zhiting, Deng, Xia, Jin, Jie, Zhang, Huihui. 2024. TPH1 inhibits bladder tumorigenesis by targeting HIF-1α pathway in bladder cancer. In Asian biomedicine : research, reviews and news, 18, 171-179. doi:10.2478/abm-2024-0023. https://pubmed.ncbi.nlm.nih.gov/39309474/