Evidence for distinct precursor pools for biliary cholesterol and primary bile acids in cebus and cynomolgus monkeys |
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Authors: | Zouhair F Stephan K C Hayes |
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Affiliation: | (1) Department of Nutrition, Harvard School of Public Health, 02115 Boston, MA;(2) Foster Biomedical Research Laboratory, Brandeis University, 02254 Waltham, MA |
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Abstract: | The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones.
To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein
free14C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus
and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis
or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic
acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus). After total bile acid
pool washout, monkeys were infused with human LDL or HDL labeled with free14C-cholesterol, and the specific activities (SA) of biliary cholesterol and primary bile acid conjugates were determined. In
both species, regardless of the lipoprotein infused, the SA of biliary cholesterol and CA were greater than those for total
bile acids and CDCA, respectively. In cynomolgus, the SA of glycine conjugates was higher for CA than CDCA, while the SA of
taurine conjugates was greater for CDCA than CA. Under these conditions, (i) infused lipoprotein free cholesterol (as either
LDL or HDL) contributed more to biliary cholesterol than to bile acids and more to CA than to CDCA; (ii) glycine conjugated
preferentially with CA rather than CDCA, while taurine was the preferred conjugate for CDCA. Further, whereas the two primary
bile acids had similar rates of synthesis and turnover in cynomolgus, basal bile acid synthesis was much greater in cebus
and the CDCA turnover appeared disproportionately large. |
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