Tryptophan analogues form adducts by cooperative reaction with aldehydes and alcohols or with aldehydes alone: possible role in ethanol toxicity.
Previous work showed that the exocyclic amino groups of nucleic acid components react quickly at ambient temperature with acetaldehyde and ethanol to yield mixed acetals [R-NH-CH(CH3)-O-C2H5]. We now find that the same type of reaction occurs readily with the nitrogen of 3-substituted indoles (e.g., indole-3-acetic acid and N-acetyltryptophan), analogues of the amino acid tryptophan. In contrast, unsubstituted indole reacts very rapidly at the carbon in ring position 2 or 3 with acetaldehyde to form bis(indolyl)ethane without ethanol entering into the reaction. Product structures have been confirmed by fast atom bombardment MS and 1H NMR. The former reaction occurs optimally in 30-50% aqueous solution below pH 4. It also proceeds more slowly and with reduced yields in aqueous media at more neutral pH. This reaction may be of biological concern, as it supplies a mechanism for protein modifications with possible toxic effects in human tissues where ethanol is metabolized.
Austin
J E
JE
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Fraenkel-Conrat
H
H
D000079:Acetaldehyde / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry* / Q000633:toxicity; D007210:Indoleacetic Acids / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry*
D007210:Indoleacetic Acids; D007211:Indoles; D000431:Ethanol; C006392:N-acetyltryptophan; C030737:indoleacetic acid; D014364:Tryptophan; D000079:Acetaldehyde