Journal of Lipid Research, Vol 27, 183-195, Copyright © 1986 by Lipid Research, Inc.
Bile acid production in human subjects: rate of oxidation of [24,25- 3H]cholesterol compared to fecal bile acid excretion
NO Davidson, HL Bradlow, EH Ahrens Jr, RS Rosenfeld and CC Schwartz
Bile acid production has been quantitated in seven subjects by methods that
compare the results of two independent approaches, namely, quantitation of
cholesterol side-chain oxidation and fecal bile acid excretion. Six
hypertriglyceridemic (HT) subjects and one normolipidemic control were
studied by both techniques. A further control subject was studied by the
cholesterol side-chain oxidation method alone. Cholesterol side-chain
oxidation was quantitated by measuring the appearance of 3H2O after
intravenous administration of [24,25-3H]cholesterol, using
multicompartmental analysis of plasma cholesterol and [3H]water specific
activity. Body water kinetics were independently defined by use of oral
D2O. Two HT subjects were restudied while they were taking cholestyramine,
16 g/day. In all ten studies, multicompartmental analysis closely simulated
the observed appearance of 3H2O. Values obtained for bile acid production
suggest that cholesterol oxidation, or bile acid input, was significantly
greater than fecal bile acid output in the HT subjects (P less than 0.05).
Cholesterol side-chain oxidation rates in the two normal subjects were
lower than those encountered in HT subjects, being similar to published
values for normal subjects both for bile acid synthesis as determined by
isotope dilution kinetics and fecal bile acid excretion. Studies conducted
with two, synthetically different, preparations of [24,25-3H]cholesterol
indicated that, in one of the two preparations, approximately 20% of the
tritium label was at positions proximal to C24. In the other preparation
examined, all of the tritium was located at, or distal to, C24. Further
studies revealed that 0.055- 0.24% of the dose was present as labile
tritium by virtue of its appearance as 3H2O following in vitro incubation
with human plasma. Provided these isotope effects are taken into account,
multicompartmental analysis of plasma [24,25-3H]cholesterol and body water
appears to be a useful technique for quantitating cholesterol oxidation in
human subjects.