Metabolism of steroid and amino acid moieties of conjugated bile acids in man: <i>II. Glycine-conjugated dihydroxy bile acids</i>

Gershon W. Hepner; Alan F. Hofmann; Paul J. Thomas

doi:10.1172/JCI106992

Metabolism of steroid and amino acid moieties of conjugated bile acids in man: II. Glycine-conjugated dihydroxy bile acids

Gershon W. Hepner, Alan F. Hofmann, and Paul J. Thomas

Published July 1, 1972 - More info

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Abstract

Chenodeoxycholyl-2,4-³H-glycine-1-¹⁴C and deoxycholyl-2,4-³H-glycine-1-¹⁴C were synthesized and administered orally to 10 healthy subjects. Distribution of radioactivity among bile acids and specific activity of steroid and amino acid moieties were determined in bile samples. ³H and ¹⁴C were measured in feces. ¹⁴C in breath was calculated from interval ¹⁴CO₂ specific activity determinations.

The daily fractional turnover of the glycine moiety of chenodeoxycholyl and deoxycholylglycines was more than three times that of the steroid moiety. Pool size of chenodeoxycholylglycine was about twice that of deoxycholylglycine, but similar fractional turnover rates of steroid and amino acid moieties suggested that intestinal absorption of the two conjugated bile acids was equally efficient (about 95%). The amount of unlabeled deoxycholic acid (newly formed by bacterial 7α-dehydroxylation) absorbed from the intestine approximated 30% of the cholic acid that was lost. ³H radioactivity remained predominantly in administered bile acid implying that, normally, secondary bile acids derived from chenodeoxycholic acid are not appreciably absorbed from the intestine and that deoxycholic acid is not hydroxylated by the liver.

Approximately 25% of administered ¹⁴C was recovered in the breath in the first 24 hr and less than 8% in the feces in 8 days; ¹⁴CO₂ excretion correlated highly with fractional turnover of the glycine moiety. ³H appeared predominantly in feces, and the rate of excretion correlated highly with the fractional turnover of the steroid moiety of bile acids. From the results in this paper plus previous measurements on the metabolism of cholylglycine, we calculated that about 6 mmoles/day of glycine is used for bile acid conjugation in health.