Fatty acid binding protein inhibits glycolithocholate sulfation.
Sulfation of hepatotoxic monohydroxy bile salts is viewed as an important detoxification mechanism. Bile salts are bound by fatty acid binding protein (FABP) with decreasing affinity as the extent of their hydroxylation increases. This binding has the potential to interfere with sulfation of monohydroxy bile salts and to augment their toxicity. FABP inhibits monohydroxy bile salt sulfation via bile salt sulfotransferases BST 1 and 2. With BST 1, the main BST, we obtained a maximal reduction of sulfation by 42.8 +/- 8.1%, using 10 microM glycolithocholate as substrate. FABP had no effect on sulfation of either 10 microM glycodeoxycholate or glycochenodeoxycholate. FABP may therefore specifically alter hepatotoxicity of lithocholate and its metabolites.
Singer
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Chemistry Department, University of Dayton, OH 45469.
Dravis
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Henkels
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Trulzsch
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D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D003864:Depression, Chemical; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D008658:Inactivation, Metabolic; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism; D012395:Rose Bengal; D012727:Sex Characteristics; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*
D001647:Bile Acids and Salts; D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012395:Rose Bengal; D008095:Lithocholic Acid; D015238:Sulfotransferases; C019786:bile-salt sulfotransferase; C027746:glycolithocholic acid