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Papers In Press, published online ahead of print October 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500178-JLR200

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Journal of Lipid Research, Vol. 46, 2221-2232, October 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

A phylogenetic survey of biliary lipids in vertebrates¹,^,

Antonio Moschetta^2,*,, Fang Xu^2,, Lee R. Hagey^2,**, Gerard P. van Berge-Henegouwen^*, Karel J. van Erpecum^*, Jos F. Brouwers, Jonathan C. Cohen, Molly Bierman, Helen H. Hobbs^,, Joseph H. Steinbach^** and Alan F. Hofmann^3,**

^* Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands
Clinica Medica "A. Murri,", Department of Internal and Public Medicine, University Hospital of Bari, Bari, Italy
Department of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
^** Department of Medicine, University of California, San Diego, CA
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

¹ Part of this work was presented at the annual meeting of the American Gastroenterological Association (San Diego, CA, May 2000) and was published as an abstract (Gastroenterology. 2000. 118: A139).

The online version of this article (available at http://www.jlr.org) contains two additional figures and four additional tables.

Published, JLR Papers in Press, August 1, 2005. DOI 10.1194/jlr.M500178-JLR200

² A. Moschetta, F. Xu, and L. R. Hagey contributed equally to this work.

³ To whom correspondence should be addressed. e-mail: ahofmann{at}ucsd.edu

Biliary lipids (bile salts, phospholipids, cholesterol, plant sterols) were determined in 89 vertebrate species (cartilaginous and bony fish, reptiles, birds, and mammals), and individual phospholipid classes were measured in 35 species. All samples contained conjugated bile salts (C₂₇ bile alcohol sulfates and/or N-acyl amidates of C₂₇ and/or C₂₄ bile acids). Phospholipids were generally absent in the bile of cartilaginous fish and reptiles and were present in low amounts relative to bile salts in bony fish and most birds. In mammals, the phospholipid-bile salt ratio varied widely. The bile from species with low biliary phospholipid-bile salt ratios often contained a high proportion of sphingomyelin, confirmed by HPLC-MS. In species with a high phospholipid-bile salt ratio, the predominant biliary phospholipid was phosphatidylcholine (PC). The phospholipid-bile salt ratio correlated weakly with the calculated weighted hydrophobic index value. Cholesterol was present in the bile of virtually all species, with plant sterols uniformly being present in only trace amounts. The cholesterol-bile salt ratio tended to be higher in mammals than in nonmammals, but bile of all species was unsaturated.

Thus, most nonmammalian vertebrates have relatively low levels of biliary phospholipid and cholesterol, suggesting that cholesterol is eliminated predominantly as bile salts. Mammals have a higher phospholipid and cholesterol to bile salt ratio, with the dominant phospholipid being PC.

Abbreviations: ABCG5, ATP binding cassette transporter G5; HI, hydrophobicity index; PC, phosphatidylcholine; RRT, relative retention time; WHI, weighted hydrophobicity index

Supplementary key words bile salts • cholesterol • gas chromatography • mass spectrometry • phosphatidylcholine • sphingomyelin

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