Quantum chemical (QM:MM) investigation of the mechanism of enzymatic reaction of tryptamine and N,N-dimethyltryptamine with monoamine oxidase A.
Organic and biomolecular chemistry November 20, 2020 Károly Kubicskó, Ö. Farkas 12 citations
The endogenous psychedelic molecule DMT, which activates sigma-1 receptors, plays a role in tissue protection, regeneration, and immunity. Using computational modeling (QM:MM calculations), the metabolism of DMT and its primary analogue tryptamine by the monoamine oxidase (MAO) enzyme was examined. The results show that DMT oxidation requires a lower activation barrier than tryptamine, suggesting a general rule that warrants further investigation. At pH 7.4, the protonated forms of these substrates enter the enzyme, and deprotonation may involve a protonated cofactor (FADH+), which yields much lower activation barriers than FAD alone.