Effects of Tryptophan and Its Metabolites on Cell Proliferation
LI Muzi1,2, ZHANG Yuchuan1,2, AYIMUGULI Abudureyimu1,2, SUN Na1,3*
Tryptophan, as an essential amino acid in the body, is involved in protein synthesis. It also produces important active compounds through the metabolic pathway of 5-hydroxytryptophan and kynurenine, inducing and activating various intracellular signaling pathways, and plays an important role in the process of cell growth, proliferation and metabolic balance, which is dose-dependent. Tryptophan can promote cell proliferation by activating mTOR (mammalian target of rapamycin) and JAK2/STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) signaling pathways and GCN2 (general control non-derepressible 2) classical stress response. 5-HTR (5-hydroxytryptamine receptor) and SETR (serotonin transporter) internalize 5-hydroxytryptamine to activate downstream signaling molecules and promote cell proliferation. However, highly expressed IDO (indoleamine 2,3-bioxygenase) consumes a large amount of tryptophan, resulting in tryptophan depletion and mass accumulation of metabolites, which can inhibit cell proliferation. At the same time, kynurenine activates AhR (aryl hydrocarbon receptor) signaling pathway, which blocks cell cycle process and inhibites cell proliferation. This paper reviews the metabolic pathways of tryptophan and its down-regulated metabolites that regulated cell proliferation. In brief, when applied to clinical targeted therapies, the rate-limiting enzymes of tryptophan metabolism could be precisely regulated for the treatment of metabolic diseases caused by abnormal cell proliferation.
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