2021 Schroepfer Medal Lecture

Wednesday, April 28, 10:45am - 11:45am (CDT)

2021 Schroepfer Medal Lecture presented by Dr. William J. Griffiths. The presentation will be livestreamed at https://annualmeeting.aocs.org/watch-the-livestream


Bile acid precursors: Intermediates in cholesterol removal or signalling molecules?

The bile acid “family” consists of mainly of C24 and C27 acids and C27 bile alcohols. The dominant pathway, at least in mammals, is the neutral pathway starting with 7α-hydroxylation of cholesterol by CYP7A1. However, there are numerous minor pathways which may have evolved as a route to biosynthesise bioactive intermediates, and it is these minor pathways that have been the main interest of the author over these last three decades. Mass spectrometry in combination with chromatography has greatly simplified the study of bile acids and their precursors over this time. Today, LC-MS instruments run with minimal operator input 24/7, something that the author could only dream of in the 1980’s, and provide reproducible chromatography, mass resolution in excess of 200,000 and mass accuracy of < 5 ppm, also delivering automated MS/MS and MSn, allowing identification of cholesterol metabolites at pg levels, and now even mass spectrometry imaging in tissue. Influenced by two previous recipients of Schroepfer Medal, Jan Sjövall and Ingemar Björkhem, the author has utilised LC-MS to study oxysterols, the primary cholesterol oxidation products, and their down-stream metabolism to bile acids. Following Sjövall-like methods of sample preparation and derivatisation the author and his collaborators have uncovered many unexpected cholesterol metabolites in body fluids and postulated pathways for their conversion to bile acids. Many of these intermediates have turned out to be biologically active, acting as ligands to e.g. nuclear receptors and G protein-coupled receptors. This leads to the question, have these minor bile acid biosynthesis pathways evolved to generate signalling molecules, with the ultimate formation of bile acids in the hepatocyte just providing an added bonus. In this paper, the author will expand on this hypothesis detailing methods for sterol identification, including new methods for sterol imaging in tissue, and discuss some of the unexpected pathways uncovered.

Add to Calendar 2021/04/28 10:45:00 2021/04/28 11:45:00 America/Chicago 2021 Schroepfer Medal Lecture 2021 Schroepfer Medal Lecture presented by Dr. William J. Griffiths. The presentation will be livestreamed at https://annualmeeting.aocs.org/watch-the-livestream


Bile acid precursors: Intermediates in cholesterol removal or signalling molecules?

The bile acid “family” consists of mainly of C24 and C27 acids and C27 bile alcohols. The dominant pathway, at least in mammals, is the neutral pathway starting with 7α-hydroxylation of cholesterol by CYP7A1. However, there are numerous minor pathways which may have evolved as a route to biosynthesise bioactive intermediates, and it is these minor pathways that have been the main interest of the author over these last three decades. Mass spectrometry in combination with chromatography has greatly simplified the study of bile acids and their precursors over this time. Today, LC-MS instruments run with minimal operator input 24/7, something that the author could only dream of in the 1980’s, and provide reproducible chromatography, mass resolution in excess of 200,000 and mass accuracy of < 5 ppm, also delivering automated MS/MS and MSn, allowing identification of cholesterol metabolites at pg levels, and now even mass spectrometry imaging in tissue. Influenced by two previous recipients of Schroepfer Medal, Jan Sjövall and Ingemar Björkhem, the author has utilised LC-MS to study oxysterols, the primary cholesterol oxidation products, and their down-stream metabolism to bile acids. Following Sjövall-like methods of sample preparation and derivatisation the author and his collaborators have uncovered many unexpected cholesterol metabolites in body fluids and postulated pathways for their conversion to bile acids. Many of these intermediates have turned out to be biologically active, acting as ligands to e.g. nuclear receptors and G protein-coupled receptors. This leads to the question, have these minor bile acid biosynthesis pathways evolved to generate signalling molecules, with the ultimate formation of bile acids in the hepatocyte just providing an added bonus. In this paper, the author will expand on this hypothesis detailing methods for sterol identification, including new methods for sterol imaging in tissue, and discuss some of the unexpected pathways uncovered.
https://annualmeeting.aocs.org/watch-the-livestream false MM/DD/YYYY 60 OPAQUE ascNbWOFrzzJsnfxRmYF90856

Wednesday, April 28, 10:45am - 11:45am (CDT)

https://annualmeeting.aocs.org/watch-the-livestream

Amy Garren, amy.garren@aocs.org