Pathways of formation of 2-, 3- and 4-bromophenol from bromobenzene. Proposed mechanism for C-S lyase reactions of cysteine conjugates.
Bromobenzene is metabolized by the rat and guinea pig to 2-, 3- and 4-bromophenol. 3-Bromophenol is formed through the sulfur-series pathway to phenols. This route involves the enterohepatic circulation; the key intermediate is the S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine derived from the 4-S-glutathione conjugate of the 3,4-oxide. A sulfonium ion C-S lyase reaction is proposed in order to account for the pyridoxal phosphate-dependent cleavage/aromatization step, and a C-S beta-lyase reaction sequence is also proposed for the formation of bromodihydrobenzene thiolols. This route of phenol formation may prove to be a general one for aromatic hydrocarbons and closely related compounds that show arene oxide conjugation with glutathione. 2-Bromophenol is formed predominately by spontaneous isomerization of the 2,3-oxide. 4-Bromophenol is formed by the sulfur-series route from the S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. Additional in vivo routes to 3- and 4-bromophenol involve dehydration/aromatization of the 3,4-dihydro-3,4-diol, possibly by way of conjugates; these routes have transient ketonic intermediates. The pathways from bromobenzene to phenols and to sulfur-containing metabolites derived from premercapturic acids show species and dosage variation.
Lertratanangkoon
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Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031.
Horning
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EC
Horning
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MG
D000818:Animals; D001969:Bromobenzenes / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D006168:Guinea Pigs; D008190:Lyases / Q000378:metabolism*; D008297:Male; D010636:Phenols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001969:Bromobenzenes; D010636:Phenols; C032038:2-bromophenol; C032036:bromobenzene; D008190:Lyases; D003545:Cysteine; C032037:4-bromophenol; C040659:3-bromophenol