C26 Bile Alcohols Research Articles

Increased urinary excretion of bile alcohol glucuronides in patients with primary biliary cirrhosis.

The bile alcohol glucuronides in urine of 12 patients with primary biliary cirrhosis (PBC), 10 patients with chronic active hepatitis (CAH), and 6 healthy volunteers were analyzed by capillary gas-liquid chromatography-mass spectrometry. In all subjects studied, the major urinary bile alcohol was found to be 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol (C26 pentol). In PBC patients, the excretion of C26 pentol (main isomer) was significantly increased above values observed in healthy volunteers (mean +/- SD = 5.2 +/- 3.5 mumol/24 h, range 1.0-13.4; versus 0.6 +/- 0.3, range 0.4-1.0). In addition, PBC patients excreted increased amounts of other bile alcohols such as isomers of C26 pentol, pentahydroxylated C27 bile alcohols (5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol) and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol) and a hexahydroxylated C26 bile alcohol (27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol). In CAH patients, the excretion of the C26 pentol main isomer ranged from 0.3 to 2.0 mumol/24 h (mean +/- SD = 0.7 +/- 0.5) and did not significantly differ from that in healthy volunteers. Moreover, the bile alcohol profile was comparable to those found in healthy volunteers and PBC patients. These findings show that total urinary bile alcohol glucuronide excretion is significantly increased in primary biliary cirrhosis. A PBC-specific urinary bile alcohol profile, however, does not exist.

Synthesis and structure of 26 (or 27)-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24S,25 xi-pentol isolated from the urine and feces of a patient with sitosterolemia and xanthomatosis.

The urine and feces of a patient with the rare inherited lipid storage disease, sitosterolemia and xanthomatosis, were analyzed. Substantial quantities of C26-bile alcohol, 26 (or 27)-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24S,25 xi-pentol along with 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24R,25-pentol, and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol were found. The structure of the C26-bile alcohol was confirmed by direct comparison (gas-liquid chromatography-mass spectrometry and thin-layer chromatography) with a standard sample synthesized from cholic acid. The configurational assignment at C-24 was determined by lanthanide-induced circular dichroism Cotton effect measurements. The increased excretion of these C26- and C27-bile alcohols suggests an abnormality of bile acid biosynthesis in this disease.

Identification of 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 xi, 25 xi,26-hexol and partial characterization of the bile alcohol profile in urine.

The nature of the bile alcohols present in urine of an infant with neonatal cholestasis has been investigated. Urine was extracted with Sep-Pak C18 cartridges and a glucuronide fraction was isolated by ion exchange chromatography on Lipidex-DEAP. Following enzymatic hydrolysis and purification on Lipidex-DEAP, the bile alcohols were isolated by high performance liquid chromatography. Fourteen compounds were studied by a combination of microchemical reactions and capillary column gas-liquid chromatography-mass spectrometry. Both C26 and C27 bile alcohols were present. Among the former, three additional isomers of the previously identified 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 xi,25 xi-pentol were detected. A new C26 bile alcohol, 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 xi,25 xi,26 -hexol, was identified, and a 27-norcholestane-pentolone with hydroxyl groups at C-24 and C-25 and a keto group in the ring system was partially characterized. The C27 bile alcohols consisted of cholestanepentols, -tetrolones, and -pentolones. 5 beta-Cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol (5 beta-bufol), one of its isomers and an isomer of cholestane-3,7,12,24,26-pentol were present. Two cholestanetetrolones and two cholestanepentolones having the keto group in the ring system were partially characterized. The hydroxyl groups in the side chain of the tetrolones were at C-24,26 and C-25,26, respectively, whereas the pentolones had hydroxyl groups at C-24,25 and C-25,26, respectively. The excretion of glucuronidated bile alcohols in urine is suggested to reflect an alternative metabolism of intermediates in the normal biosynthesis of bile acids.

Urinary excretion of bile alcohols in normal children and patients with alpha 1-antitrypsin deficiency during development of liver disease.

Healthy infants and children were found to excrete bile alcohol glucuronides in urine. Following isolation and hydrolysis, the bile alcohols were estimated by capillary gas-liquid chromatography. The daily urinary excretion of the major compound, 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 xi, 25 xi-pentol (a C26 bile alcohol), ranged from 0.1 to 1.1 mumol/24 h per m2 body surface area for healthy infants and children. Two groups of patients with alpha 1-antitrypsin deficiency (phenotype PiZ) were also studied during infancy and childhood, and biochemical liver function tests and liver morphology were compared to the excretion of bile alcohols. The highest excretion of the C26 bile alcohol in urine was found in patients with alpha 1-antitrypsin deficiency and juvenile cirrhosis (2.1-8.4 mumol 24 h-1 m-2) regardless of preceding neonatal cholestasis. Patients with alpha 1-antitrypsin deficiency, neonatal cholestasis and subsequent fibrosis or normal liver morphology excreted bile alcohols within the normal range. The C26 bile alcohol constituted an average of 36% of the total bile alcohols in forty-three urine samples. This percentage was about the same in the three groups studied. The findings suggest that determination of urinary bile alcohols may be a valuable non-invasive diagnostic tool for patients with or at risk of developing liver cirrhosis.

Metabolism of bile alcohols, 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-26,27-dinor-5 beta-cholestan-24-one, in rats.

24-Nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-26,27-dinor-5 beta-cholestan-24-one were administered intraperitoneally to bile fistula rats, and the metabolites excreted in the bile were analyzed. No formation of bile acids from these bile alcohols was observed. 7 alpha,12 alpha,25-Trihydroxy-24-nor-5 beta-cholestane-3 alpha-O-(beta-D-glucopyranosid)uronic acid was identified as the only biliary metabolite of the 24-nor-5 beta-cholestanetetrol. The major metabolite of the trihydroxy-26,27-dinor-5 beta-cholestanone was 7 alpha,12 alpha-dihydroxy-24-oxo-26,27-dinor-5 beta-cholestane-3 alpha-O-(beta-D-glucopyranosid)uronic acid, and the minor metabolite was the glucurono conjugate of 26,27-dinor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 beta-tetrol. The results indicated that in rat liver these C25- and C26-bile alcohols, in contrast to C27-bile alcohols, were not converted into bile acids, and that the glucuronide production became necessary for hepatic elimination of the accumulated bile alcohols.

Isolation of new C26 bile alcohols from bullfrog bile.

The bile alcohol constituents of bullfrog were examined to give four new C26 bile alcohols along with three known bile alcohols, 5α-cyprinol, 5α-ranol, and 5β-ranol. On the basis of the spectral data and the direct comparison with synthetic samples, the structures of the new bile alcohols were established to be four 27-norcholestane-3α, 7α, 12α, 24-tetrols isomeric at C-5 and C-24, (I), (III), (VII), and (VIII).