Bile Acid Synthesis in Man: Metabolism of 7α-Hydroxycholesterol-14C and 26-Hydroxycholesterol-3H

Abstract

The pathways of bile acid synthesis in man were evaluated by studying the metabolism of 7a-hydroxycholesterol-4-14C and 26-hydroxycholesterol-16, 22-3H administered parenterally to individuals requiring external biliary drainage. Techniques for the identification of metabolites were thin-layer chromatography, column chromatography, gas-liquid chromatography with stream splitting, and crystallization to constant specific activity. It was found that both compounds were rapidly metabolized to bile acids and excreted in bile. Of the total radioactivity recovered in bile as bile acids, 87% of the 26-hydroxycholesterol-3H and 90% of the 7a-hydroxycholesterol-14C was found to be metabolized to both chenodeoxycholate and cholate. Compared to 7a-hydroxycholesterol, a greater proportion of 26-hydroxycholesterol was found to be metabolized to chenodeoxycholate.These findings indicate that both 7a-hydroxycholesterol and 26-hydroxycholesterol can be intermediates in the metabolism of cholesterol to bile acids in man. The observation that conversion to cholate takes place less readily after C-26 hydroxylation is consistent with previous findings in other species.

Bile acid excretion: the alternate pathway in the hamster.

“…1). In 18 hamsters at 24 h the mean value was 454±+176,ug/ml SD and fell to 73+48,ug/ml SD. Cholic acid ranged from 61 to 86% and chenodeoxycholate from 10 to 31%.…”

“…Thus, the hamster, unlike the rat or mouse does not synthesize muricholic acids from cholesterol, 26-hydroxycholesterol or 7a-hydroxycholesterol (18,21) and similar to man, has a bile acid pool consisting of mostly the glycine and taurine conjugates of cholic and chenodeoxycholic acids with lesser amounts of deoxycholate and lithocholate.…”

“…Exactly 0.1 ml of 0.9% saline containing 2.5% human serum albumin and a mixture of trace amounts of 14C-24 chenodeoxycholate and cholate was injected into the jugular vein using a Hamilton syringe under brief ether anesthesia. At 24 h, bile was aspirated from the gallbladder and biliary tree, and the specific activity of each bile acid determined after hydrolysis and thin-layer chromatography by GLC and liquid scintillation spectrometry by standard techniques previously described in detail (18).…”

Regulation of low density lipoprotein metabolism by 26‐hydroxycholesterol in human fibroblasts

“…25-Hydroxycholesterol is considered an autooxidation product of cholesterol [8,17], and its occurrence in vivo as part of a metabolic pathway is disputed [I0,18]. In contrast, 26-hydroxycholesterol is the result of mitochondrial C27-steroid 26-hydroxylase [19,20], is an intermediate in the synthesis of bile acids [21], and is present in the serum of normal adults [7].…”

Membrane-Protein Interactions Contribute to Efficient 27-Hydroxylation of Cholesterol by Mitochondrial Cytochrome P450 27A1

“…P450 7A1 catalyzes 7␣-hydroxylation of cholesterol, the first and rate-limiting step in the classical bile acid biosynthetic pathway (2,3), whereas P450 27A1 carries out 27-hydroxylation of cholesterol, the first step in the alternative bile acid biosynthesis (4,5). P450 27A1 also catalyzes multiple oxidation reactions at the C-27 atom of bile acid intermediates in the classical bile acid biosynthetic pathway.…”