Abstract
Sulfate esterification has been shown previously to be a prominent feature of lithocholate metabolism in man. These studies were undertaken to ascertain whether this metabolic pathway is also present in rats, and to investigate the physiological significance of bile acid sulfate formation. Lithocholic acid-24-(14)C was administered to bile fistula rats, and sulfated metabolites were identified in bile by chromatographic and appropriate degradative procedures. They constituted only a small fraction (2-9%) of the total metabolites but a more significant fraction (about 20%) of the secreted monohydroxy bile acids, most of the lithocholate having been hydroxylated by the rat liver. When sulfated glycolithocholate was administered orally, it was absorbed from the intestine without loss of the sulfate, presumably by active transport, and secreted intact into the bile. In comparison with non-sulfated lithocholate, an unusually large fraction (24%) of the sulfated bile acid was excreted in the urine, and fecal excretion took place more rapidly. Both the amino acid and sulfate moieties were extensively removed prior to excretion in the feces. Hydroxylation of bile acid sulfates or sulfation of polyhydroxylated bile acids did not occur to any great extent, if at all.
Highlights
Sulfate esterification has been shown previously to be a prominent feature of lithocholate metabolism in man
Lithocholic acid-24-14Cwas administered to bile fistula rats, and sulfated metabolites were identified in bile by chromatographic and appropriate degradative procedures
T h e present series of experiments was undertaken to answer the following questions: ( a ) Does sulfation of lithocholate occur in the rat, a n d if so, is intestinal absorption a requisite for sulfation? (b) Can sulfated bile salts be absorbed from the r a t intestine in vivo? (c) Does sulfation alter the biochemical pathways of lithocholate metabolism in vivo? (d) Does sulfation affect the route and rate of lithocholate excretion? T h e results demonstrate that sulfation of lithocholates does occur in rats, with consequent alterations in their patterns of metabolism and excretion
Summary
Sulfate esterification has been shown previously to be a prominent feature of lithocholate metabolism in man. In comparison with nonsulfated lithocholate, an unusually large fraction (24%) of the sulfated bile acid was excreted in the urine, and fecal excretion took place more rapidly. Bile fistula rats were used to determine whether a sulfated lithocholate could be absorbed from the intestine in vivo.
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