Lertratanangkoon K, Horning E C, Horning M G
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031.
Res Commun Chem Pathol Pharmacol. 1993 Jun;80(3):259-82.
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.
溴苯在大鼠和豚鼠体内代谢生成2-、3-和4-溴苯酚。3-溴苯酚通过硫系列途径生成酚类。该途径涉及肠肝循环；关键中间体是由3,4-氧化物的4-S-谷胱甘肽共轭物衍生而来的S-(2-羟基-4-溴环己-3,5-二烯基)-L-半胱氨酸。为了解释磷酸吡哆醛依赖性裂解/芳构化步骤，提出了一个锍离子C-S裂解酶反应，并且还提出了一个C-Sβ-裂解酶反应序列用于生成溴二氢苯硫醇。对于与谷胱甘肽形成芳烃氧化物共轭的芳烃和密切相关的化合物，这种酚类形成途径可能是一种普遍途径。2-溴苯酚主要由2,3-氧化物的自发异构化形成。4-溴苯酚由S-(2-羟基-5-溴环己-3,5-二烯基)-L-半胱氨酸通过硫系列途径形成。生成3-和4-溴苯酚的其他体内途径涉及3,4-二氢-3,4-二醇的脱水/芳构化，可能通过共轭物的方式；这些途径有短暂的酮中间体。从溴苯到酚类以及到源自前巯基尿酸的含硫代谢物的途径显示出物种和剂量差异。
