Identification of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic acid in human bile: reflection of a new pathway in bile acid metabolism in humans.
The chemical synthesis, nuclear magnetic resonance, and mass spectrometric characteristics of the first C-4 hydroxylated bile acid analogues are described. The data definitively confirm, for the first time, the identity of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic acid in human fetal gallbladder bile. In addition, 3 alpha,4 beta,7 alpha-12 alpha-tetrahydroxy-5 beta-cholanoic was identified in the feces from healthy newborn infants many days after birth, indicating a hepatic origin for C-4 hydroxylation of bile acids. To our knowledge bile acids hydroxylated at the C-4 position of the steroid nucleus have never been previously recognized in any mammalian species. The finding of this novel bile acid which accounts for 5-15% of the total biliary bile acids in early gestation indicates that C-4 hydroxylation is a unique and important metabolic pathway in early human development.
Dumaswala
R
R
Department of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, Cincinnati, OH 45229-2899.
Setchell
K D
KD
Zimmer-Nechemias
L
L
Iida
T
T
Goto
J
J
Nambara
T
T
D001646:Bile / Q000032:analysis*; D001647:Bile Acids and Salts / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002793:Cholic Acids / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D005333:Fetus; D005704:Gallbladder / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy
D001647:Bile Acids and Salts; D002793:Cholic Acids; C061275:3,4,7-trihydroxycholanoic acid