Characterization of bovine phenol sulfotransferases: evidence of a major role for SULT1B1 in the liver

Abstract

1. Cattle are an important component of the human food chain. Drugs used either legally or illegally in cattle may therefore enter the food chain and it is thus important to understand pathways of drug metabolism in this species, including sulfation catalyzed by the sulfotransferases (SULTs). 2. In this study, we have analyzed the sulfation of 4-nitrophenol and other compounds in male and female bovine liver and characterized recombinant bovine SULT isoforms 1A1 and 1B1 expressed in Escherichia coli. 3. We found that, in contrast to most other mammalian species, the major phenol sulfotransferase SULT1A1 is not expressed in bovine liver. Rather SULT1B1 seems to be a major form in both male and female bovine liver. 4. We also identified kinetic differences between bovine and human SULT1A1 and, using the human SULT1A1 crystal structure, identified two amino acid positions in the active site of bovine SULT1A1 (Ile89Val and Phe247Val) that may be responsible for these differences.

Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals

“…SULTs catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. SULT1B1 sulfates many exogenous substances, including 4-nitrophenol, silymarin, daphnetin, 6-gingerol, dotinurad, curcuminoid, brivanib, and 6-o-desmethylnaproxen ( 39 – 46 ).…”

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

“…Human UGTs, GSTs and SULTs are the main conjugative DMEs, participating in the metabolism of drugs most commonly used in therapy [ 4 , 175 , 176 ]. At present, limited information is available about SULT expression, regulation and catalytic activity [ 177 ], but phenol and 2-naphthol have already been used as probe substrates in ruminants [ 98 , 100 , 102 ]. The sulfotransferase 2A1- like is the predominant SULT isoform in bovine liver, but PB exposure did not affect its mRNA levels [ 44 ].…”

Evaluation of Phenol Sulfotransferase (SULT1A1) Ligand Binding Order

“…Although the structure of bSULT1A1 has not been determined directly, its extensive identity and similarity to the human enzyme have allowed the modeling of its structure [12,36]. We have also applied lessons learned from other SULTs regarding conformational changes between the determined ligand-bound states and the free or apo form (Methods).…”