Biosynthesis of N,N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases.
Melissa M. Gomes, J. B. Coimbra, R. O. Clara, F. Dörr, A. C. R. Moreno, J. Chagas, Sergio Tufik, E. Pinto, L. Catalani, Ana Čampa
Biochemical Pharmacology April 1, 2014 DOI: 10.1016/j.bcp.2014.01.035 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | SK-Mel-147 melanoma cell line; also horseradish peroxidase and MPO from PMA-activated neutrophils |
| Intervention | DMT |
| Duration | 24 hours |
| Topics | 5-MeO-DMT DMT |
| Citations | 21 |
| Key points | DMT and its metabolites, including DMFK, hydroxy-DMT, and indole acetic acid, were identified in melanoma cell cultures, and DMT oxidation is catalyzed by peroxidases via the common peroxidase cycle. |
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.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 9
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Frontiers in Neuroscience August 6, 2018
- Exploring DMT: Endogenous role and therapeutic potential. Neuropharmacology May 1, 2025
- Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate Journal of Psychopharmacology August 1, 2022
- Immunological Effects of Ayahuasca in Humans Journal of Psychoactive Drugs October 20, 2014
and 4 more in the library
Cites 11
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study PLoS One August 8, 2012
- Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds Science August 4, 1961
- A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. Drug Testing and Analysis 2012
- Metabolism and disposition of N,N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca Drug Testing and Analysis April 19, 2012
and 6 more in the library