Title: Sulfonation and glucuronidation of hydroxylated bromodiphenyl ethers in human liver.
Authors: Cisneros, Katherine V; Agarwal, Vinayak; James, Margaret O
Published In Chemosphere, (2019 Jul)
Abstract: Hydroxylated bromodiphenyl ethers (OH-BDEs) can arise from monooxygenation of anthropogenic BDEs or through natural biosynthetic processes in marine organisms, and several OH-BDEs have been shown to be toxic. OH-BDEs are expected to form sulfate and glucuronide conjugates that are readily excreted, however there is little information on these pathways. We examined the human hepatic glucuronidation and sulfonation of 6-OH-BDE47, 2-OH-BDE68, 4-OH-BDE68 and 2-OH-6'methoxy-BDE68. Human liver microsomes and cytosol were from de-identified female and male donors aged 31 to 75 under an exempt protocol. Recombinant human SULT1A1, 1B1, 1E1 and 2A1 enzymes were prepared from bacterial expression systems. Sulfonation and glucuronidation of each OH-BDE were studied using radiolabeled co-substrates, 3'phosphoadenosine-5'phospho-35S-sulfate or uridine diphospho-β-D-14C-glucuronic acid in order to quantify the sulfated or glucuronidated products. The OH-BDEs studied were more efficiently glucuronidated than sulfonated. Of the compounds studied, 2-OH-BDE68 was the most readily conjugated, and exhibited an efficiency (Vmax/KM) of glucuronidation of 0.274 ± 0.125 mL/min/mg protein, mean ± S.D., n = 3, while that for sulfonation was 0.179 ± 0.030 mL/min/mg protein. For both pathways, all Km values were in the low μM range. Studies with human SULT enzymes showed that sulfonation of these four substrates was readily catalyzed by SULT1B1 and SULT1E1. Much lower activity was found with SULT1A1 and SULT2A1. Assuming that the glucuronide and sulfate conjugates are non-toxic and readily excreted, as is the case for most such conjugates, these studies suggest that OH-BDEs should not accumulate in people to the same extent as the parent BDEs.
PubMed ID: 30925405
MeSH Terms: Adult; Aged; Cytosol/chemistry; Ethers/chemistry*; Female; Glucuronides/chemistry*; Humans; Hydroxylation; Liver/metabolism*; Liver/ultrastructure; Male; Microsomes, Liver/metabolism; Middle Aged; Polybrominated Biphenyls/chemistry*; Sulfates/chemistry*