Metabolism of 5-Hydroxytryptamine by Brain Synaptosomes and Microsomes in the Presence of Cysteine and Glutathione

Article abstract of DOI:10.1021/jm00092a018

Incubation of 5-hydroxytryptamine (1) with L-cysteine and pig or bovine brain microsomes and an NADPH-generating system or with synaptosomes results in the rapid formation of the (2R,4R)- and (2S,4R)-epimers of 2-<(5-hydroxy-1H-indol-3-yl)methyl>thiazolidine.Incubation of 1 and glutathione under the same experimental conditions yields the (2R,4R)- and (2S,4R)-epimers of α-amino-4-<carbonyl>-2-<(5-hydroxy-1H-indol-3-yl)methyl>-?-oxo-3-thiazolidinepentanoic acid.These various thiazolidine derivatives are formed by nucleophilic addition of the thiol residues of cysteine or glutathione to the aldehyde group of 5-hydroxyindole-3-acetaldehyde (2), the primary product of the monoamine oxidase-mediated oxidative deamination of 1.The facile reaction of cysteine and glutathione with 2 might represent a mechanism designed to scavenge the biogenic aldehyde and therefore to prevent its alkylation of key intraneuronal protein nucleophiles.