Metabolism of ursocholic acid in humans: conversion of ursocholic acid to deoxycholic acid.
To study the metabolism of ursocholic acid, control subjects were injected with radiolabeled cholic and ursocholic acids before and after 1 wk of 900 mg/day oral ursocholic acid. Daily samples of bile were obtained, and biliary bile acids were extracted and purified to determine bile acid kinetics. During ursocholic acid therapy ursocholic acid became the principal bile acid (35% +/- 3% of total bile acids, mean +/- S.E.M.), and the percentage of biliary cholic and chenodeoxycholic acids decreased (p less than 0.05). Cholic acid production fell from 190 +/- 15 mg/day to 135 +/- 20 mg/day (p = 0.078). The total bile acid pool was increased twofold (p less than 0.05), whereas the deoxycholic acid pool was enlarged from 440 +/- 170 mg to 1,175 +/- 90 mg (p less than 0.02). As much as 28% of the fed ursocholic acid was excreted in the urine, 85% as the free acid and 15% as the glycine conjugate. During treatment, ursocholic acid became the source for 69% +/- 11% of biliary deoxycholic acid. The time course of the deoxycholic acid specific activity was modeled as a single pool precursor-product system with a variable time delay for the C-7-dehydroxylation of cholic and ursocholic acids (mean delay 0.86 +/- 0.11 days, p less than 0.001 vs. zero delay). Most of this delay probably arises from a slow process of bacterial C-7-dehydroxylation within the colon. These results demonstrate that during ursocholic acid therapy the synthesis of primary bile acids continues whereas the formation of secondary bile acids is greatly increased.
Tint
G S
GS
Veterans Administration Medical Center, East Orange, New Jersey 07019.
Batta
A K
AK
Dayal
B
B
Kovell
N
N
Shefer
S
S
Salen
G
G
D000328:Adult; D001646:Bile / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D003840:Deoxycholic Acid / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D013997:Time Factors
D002793:Cholic Acids; D003840:Deoxycholic Acid; D019826:Cholic Acid; C030712:ursocholic acid