Evidence for the formation of Michael adducts from reactions of (E,E)-muconaldehyde with glutathione and other thiols.
Glutathione induces the rapid isomerization of (Z,Z)-muconaldehyde to (E,E)-muconaldehyde via (E,Z)-muconaldehyde, probably via reversible Michael addition of the thiol to one of the enal moieties of the muconaldehyde. Reactions of (E,E)-muconaldehyde with glutathione (in the presence and absence of equine glutathione S-transferase), phenylmethanethiol, N-acetyl-l-cysteine, and N-acetyl-l-cysteine methyl ester were investigated using mass spectrometric techniques. In each case, evidence was obtained for the formation of Michael adducts, e.g., reaction between (E,E)-muconaldehyde and glutathione gave 4-glutathionyl-hex-2-enedial and 3,4-bis-glutathionyl-hexanedial. These experiments suggest that (Z,Z)-muconaldehyde, a putative metabolite of benzene, could lead to the long established urinary metabolite of benzene, (E,E)-muconic acid, via glutathione-mediated isomerization to (E,E)-muconaldehyde.
Henderson
Alistair P
AP
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7431, USA. alistair@email.unc.edu
Bleasdale
Christine
C
Delaney
Kirsty
K
Lindstrom
Andrew B
AB
Rappaport
Stephen M
SM
Waidyanatha
Suramya
S
Watson
William P
WP
Golding
Bernard T
BT
D000447:Aldehydes / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D005982:Glutathione Transferase; D007202:Indicators and Reagents; D007536:Isomerism; D007700:Kinetics; D013058:Mass Spectrometry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000447:Aldehydes; D007202:Indicators and Reagents; D013438:Sulfhydryl Compounds; C034476:muconaldehyde; D005982:Glutathione Transferase; D005978:Glutathione