TY - JOUR
T1 - The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation
T2 - history, biochemistry, and microbiology
AU - Ridlon, Jason M.
AU - Daniel, Steven L.
AU - Gaskins, H. Rex
N1 - Publisher Copyright:
© 2023 THE AUTHORS.
PY - 2023/8
Y1 - 2023/8
N2 - Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived “primary” bile acids from “secondary” bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuelsson-Bergström model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Björkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.
AB - Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived “primary” bile acids from “secondary” bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuelsson-Bergström model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Björkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.
KW - allo-bile acids
KW - bile acid dehydroxylation
KW - bile acids
KW - enterohepatic circulation
KW - gut microbiome
KW - intestinal lipid metabolism
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U2 - 10.1016/j.jlr.2023.100392
DO - 10.1016/j.jlr.2023.100392
M3 - Review article
C2 - 37211250
AN - SCOPUS:85168798957
SN - 0022-2275
VL - 64
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 8
M1 - 100392
ER -