Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications.

ABSTRACT

PURPOSE OF REVIEW To describe the role of Tryptophan (Trp) metabolism and Kynurenine (Kyn) metabolites in nutritional and metabolic changes in cancer. RECENT FINDINGS: Trp is in part utilized for protein and neurotransmitters biosynthesis, but more than 95% is implicated in Kyn pathways. In this molecular cascade, metabolites are produced with distinct biological activities regulating the immune response and neurotransmission with potential implications in malnutrition/cachexia during cancer. Immune dysfunction is a phenomenon occurring during cancer and malnutrition. Kyn metabolites regulate lymphocytes activity and recent data in animals showed that the inhibition of indoleamine-2,3-dioxygenase (IDO) via 1-methyl-tryptophan determines partial amelioration of inflammation, but no positive effects on the preservation of muscularity were observed. Kynurenines seem to contribute to muscle catabolism via NAD+ biosynthesis and ROS generation. Trp metabolism via the serotonin biosynthesis is involved in appetite control in cancer. Moreover, kynurenines have a role in determining fatigue in conditions associated with inflammation. SUMMARY: Trp metabolism has implications in immune and energy balance in cancer. The modulation of Trp and kynurenines have impact on central nervous system mechanisms, including appetite, fatigue, and muscle wasting/cachexia. Research focusing on these clinical implications will open new scenario for therapeutic interventions aimed at counteracting nutritional derangements in cancer.