Metabolism of 5-hydroxytryptamine by brain synaptosomes and microsomes in the presence of cysteine and glutathione.
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 alpha-amino-4-[[(carboxymethyl)amino]carbonyl]-2-[(5-hydroxy-1H- indol-3-yl)methyl]-delta-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.
Singh
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Department of Chemistry and Biochemistry, University of Oklahoma, Norman 73019.
Dryhurst
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism*; D015394:Molecular Structure; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism*; D013552:Swine; D013574:Synaptosomes / Q000378:metabolism*
D012701:Serotonin; D005978:Glutathione; D003545:Cysteine