title: Biosynthesis of N,N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases.
abstract: Tryptophan (TRP) is essential for many physiological processes, and its metabolism changes in some diseases such as infection and cancer. The most studied aspects of TRP metabolism are the kynurenine and serotonin pathways. A minor metabolic route, tryptamine and N,N-dimethyltryptamine (DMT) biosynthesis, has received far less attention, probably because of the very low amounts of these compounds detected only in some tissues, which has led them to be collectively considered as trace amines. In a previous study, we showed a metabolic interrelationship for TRP in melanoma cell lines. Here, we identified DMT and N,N-dimethyl-N-formyl-kynuramine (DMFK) in the supernatant of cultured SK-Mel-147 cells. Furthermore, when we added DMT to the cell culture, we found hydroxy-DMT (OH-DMT) and indole acetic acid (IAA) in the cell supernatant at 24 h. We found that SK-Mel-147 cells expressed mRNA for myeloperoxidase (MPO) and also had peroxidase activity. We further found that DMT oxidation was catalyzed by peroxidases. DMT oxidation by horseradish peroxidase, H2O2 and MPO from PMA-activated neutrophils produced DMFK, N,N-dimethyl-kynuramine (DMK) and OH-DMT. Oxidation of DMT by peroxidases apparently uses the common peroxidase cycle involving the native enzyme, compound I and compound II. In conclusion, this study describes a possible alternative metabolic pathway for DMT involving peroxidases that has not previously been described in humans and identifies DMT and metabolites in a melanoma cell line. The extension of these findings to other cell types and the biological effects of DMT and its metabolites on cell proliferation and function are key questions for future studies.
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil.
authors: Melissa M
authors: MM
authors: Gomes
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil.
authors: Janine B
authors: JB
authors: Coimbra
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil.
authors: Renan O
authors: RO
authors: Clara
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil.
authors: Felipe A
authors: FA
authors: Dörr
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil.
authors: Ana Carolina R
authors: AC
authors: Moreno
authors: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Jair R
authors: JR
authors: Chagas
authors: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Sérgio
authors: S
authors: Tufik
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil.
authors: Ernani
authors: E
authors: Pinto
authors: Department of Fundamental Chemistry, Universidade de Sao Paulo, São Paulo, Brazil.
authors: Luiz H
authors: LH
authors: Catalani
authors: Department of Clinical Chemistry and Toxicology, Universidade de São Paulo, São Paulo, Brazil. Electronic address: anacampa@usp.br.
authors: Ana
authors: A
authors: Campa
mesh_terms: D045744:Cell Line, Tumor; D006735:Horseradish Peroxidase / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D008545:Melanoma; D004130:N,N-Dimethyltryptamine / Q000096:biosynthesis* / Q000737:chemistry; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*
chemical_list: D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D010544:Peroxidases; D009195:Peroxidase; D004130:N,N-Dimethyltryptamine
keywords: Horseradish peroxidase (HRP); Melanoma; Myeloperoxidase (MPO); N,N-dimethyltryptamine (DMT); Tryptamine