Bile salts of vertebrates: structural variation and possible evolutionary significance

Biliary bile salt composition of 677 vertebrate species (103 fish, 130 reptiles, 271 birds, 173 mammals) was determined. Bile salts were of three types: C-27 bile alcohols, C-27 bile acids, or C-24 bile acids, with default hydroxylation at C-3 and C-7. C-27 bile alcohols dominated in early evolving fish and amphibians; C-27 bile acids, in reptiles and early evolving birds. C-24 bile acids were present in all vertebrate classes, often with C-27 alcohols or with C-27 acids, indicating two evolutionary pathways from C-27 bile alcohols to C-24 bile acids: a) a 'direct' pathway and b) an 'indirect' pathway with C-27 bile acids as intermediates. Hydroxylation at C-12 occurred in all orders and at C-16 in snakes and birds. Minor hydroxylation sites were C-1, C-2, C-5, C-6, and C-15. Side chain hydroxylation in C-27 bile salts occurred at C-22, C-24, C-25, and C-26, and in C-24 bile acids, at C-23 (snakes, birds, and pinnipeds). Unexpected was the presence of C-27 bile alcohols in four early evolving mammals. Bile salt composition showed significant variation between orders but not between families, genera, or species. Bile salt composition is a biochemical trait providing clues to evolutionary relationships, complementing anatomical and genetic analyses. Hofmann, A. F., L. R. Hagey, and M. D. Krasowski. Bile salts of vertebrates: structural variation and possible evolutionary significance. J. Lipid Res. 2010. 51: 226-246.