Quantum Chemical Study of the Hydrolysis of Oxidized Endogenous Psychedelic N,N-Dimethyltryptamine
Károly Kubicskó, Richárd Dezső Kovács, Ödön Farkas
Study at a glance
AI-extracted from the abstract| Characteristics | Computational study |
|---|---|
| Topics | 5-MeO-DMT DMT |
| Key points | The hydrolysis of imDMT+ to indole-3-acetaldehyde and dimethylamine can occur without enzymatic assistance, provided that one or two explicit water molecules are included in the computational model to obtain accurate activation barriers. |
Abstract
The metabolism of biogenic N,N-dimethyltryptamine (DMT) starts with its enzymatic oxidation to indole-3-N,N-dimethylethaniminium cation (imDMT+) by monoamine oxidase (MAO). Following this reaction, a non-enzymatic hydrolysis occurs, yielding indole-3-acetaldehyde (IAL) and dimethylamine (DMA). In our in silico study, using a hybrid DFT method at the M06-2X/aug-cc-pVDZ level, we examined the necessity of explicit water molecules to accurately model the hydrolysis. Our calculations revealed that despite an implicit continuum solvent model, one or two explicit solvent water molecules should be added to obtain meaningful activation barriers. Thus, we demonstrate that the hydrolysis can occur in a human cell without enzymaticassistance, paving the way for deeper understanding of DMT metabolism.
Citations in the library
Cites 2
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- Quantum chemical (QM:MM) investigation of the mechanism of enzymatic reaction of tryptamine and N,N-dimethyltryptamine with monoamine oxidase A. Organic & Biomolecular Chemistry November 20, 2020