Gene structure of pig sterol 12alpha-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21).
Cholic acid is the major trihydroxy bile acid formed in most mammals. The domestic pig (Sus scrofa) is an exception. The bile of adult pig is devoid of cholic acid whereas hyocholic acid is found in amounts equal to that of cholic acid in humans. The pathway leading to formation of hyocholic acid is believed to be species-specific and to have evolved in the pig to compensate for a nonexistent or deficient cholic acid biosynthesis. However, a high level of cholic acid has recently been found in the bile of fetal pig. Here we describe that a gene encoding the key enzyme in cholic acid biosynthesis, the sterol 12alpha-hydroxylase (CYP8B1), is in fact present in the pig genome. The deduced amino acid sequence shows 81% identity to the human and rabbit orthologues. CYP8B1 mRNA is expressed at significant levels in fetal pig liver. Both CYP8B1 and the key enzyme in hyocholic acid formation, taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21), were found to be expressed in pig liver in a developmental-dependent but opposite fashion.
Lundell
Kerstin
K
Division of Biochemistry, Department of Pharmaceutical Biosciences, University of Uppsala, Box 578, S-751 23 Uppsala, Sweden. Kerstin.Lundell@farmbio.uu.se
Wikvall
Kjell
K
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D019826:Cholic Acid / Q000096:biosynthesis; D002793:Cholic Acids / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005333:Fetus; D040461:Gene Components; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D013253:Steroid 12-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D013552:Swine / Q000235:genetics*
D002793:Cholic Acids; D012333:RNA, Messenger; C004821:muricholic acid; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D013253:Steroid 12-alpha-Hydroxylase; C095246:taurochenodeoxycholic acid 6-alpha-hydroxylase; D019826:Cholic Acid