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Title: Oxidoreduction of different hydroxyl groups in bile acids during their enterohepatic circulation in man

Abstract

The extent of oxidoreduction of the 3 alpha-, 7 alpha- and 12 alpha-hydroxyl groups in bile acids during the enterohepatic circulation in man was studied with the use of (3 beta-/sup 3/H)-labeled deoxycholic acid and cholic acid, (7 beta-/sup 3/H)-labeled cholic acid, and (12 beta-/sup 3/H)-labeled deoxycholic acid and cholic acid. Each (/sup 3/H)-labeled bile acid was given per os to healthy volunteers, together with the corresponding (24-/sup 14/C)-labeled bile acid. The rate of oxidoreduction was calculated from the decrease in the ratio between /sup 3/H and /sup 14/C in the respective bile acid isolated from duodenal contents collected at different time intervals after administration of the labeled bile acids. The mean fractional conversion rate was found to be 0.29 day-1 for the 3 alpha-hydroxyl group in deoxycholic acid (n = 2), 0.18 day-1 for the 12 alpha-hydroxyl group in deoxycholic acid (n = 6), 0.09 day-1 for the 3 alpha-hydroxyl group in cholic acid (n = 3), 0.05 day-1 for the 7 alpha-hydroxyl group in cholic acid (n = 2), and 0.03 day-1 for the 12 alpha-hydroxyl group in cholic acid (n = 2). The extent of oxidoreduction of the 12 alpha-hydroxyl group in (12 beta-/sup 3/H)-labeled deoxycholic acidmore » given to two patients operated with subtotal colectomy and ileostomy was markedly reduced (less than 20% of normal).« less

Authors:
; ; ;
Publication Date:
Research Org.:
Huddinge Univ. Hospital, Sweden
OSTI Identifier:
5592275
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Lipid Res.; (United States); Journal Volume: 2
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BILE ACIDS; LABELLING; REDOX REACTIONS; CARBON 14 COMPOUNDS; CHOLIC ACID; DIGESTIVE SYSTEM DISEASES; HYDROXYLATION; MAN; PATIENTS; SURGERY; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; CARBOXYLIC ACIDS; CHEMICAL REACTIONS; DISEASES; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; MEDICINE; ORGANIC ACIDS; ORGANIC COMPOUNDS; PRIMATES; STEROIDS; STEROLS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques; 550901 - Pathology- Tracer Techniques

Citation Formats

Bjoerkhem, I.L., Liljeqvist, L., Nilsell, K., and Einarsson, K.. Oxidoreduction of different hydroxyl groups in bile acids during their enterohepatic circulation in man. United States: N. p., 1986. Web.
Bjoerkhem, I.L., Liljeqvist, L., Nilsell, K., & Einarsson, K.. Oxidoreduction of different hydroxyl groups in bile acids during their enterohepatic circulation in man. United States.
Bjoerkhem, I.L., Liljeqvist, L., Nilsell, K., and Einarsson, K.. Sat . "Oxidoreduction of different hydroxyl groups in bile acids during their enterohepatic circulation in man". United States. doi:.
@article{osti_5592275,
title = {Oxidoreduction of different hydroxyl groups in bile acids during their enterohepatic circulation in man},
author = {Bjoerkhem, I.L. and Liljeqvist, L. and Nilsell, K. and Einarsson, K.},
abstractNote = {The extent of oxidoreduction of the 3 alpha-, 7 alpha- and 12 alpha-hydroxyl groups in bile acids during the enterohepatic circulation in man was studied with the use of (3 beta-/sup 3/H)-labeled deoxycholic acid and cholic acid, (7 beta-/sup 3/H)-labeled cholic acid, and (12 beta-/sup 3/H)-labeled deoxycholic acid and cholic acid. Each (/sup 3/H)-labeled bile acid was given per os to healthy volunteers, together with the corresponding (24-/sup 14/C)-labeled bile acid. The rate of oxidoreduction was calculated from the decrease in the ratio between /sup 3/H and /sup 14/C in the respective bile acid isolated from duodenal contents collected at different time intervals after administration of the labeled bile acids. The mean fractional conversion rate was found to be 0.29 day-1 for the 3 alpha-hydroxyl group in deoxycholic acid (n = 2), 0.18 day-1 for the 12 alpha-hydroxyl group in deoxycholic acid (n = 6), 0.09 day-1 for the 3 alpha-hydroxyl group in cholic acid (n = 3), 0.05 day-1 for the 7 alpha-hydroxyl group in cholic acid (n = 2), and 0.03 day-1 for the 12 alpha-hydroxyl group in cholic acid (n = 2). The extent of oxidoreduction of the 12 alpha-hydroxyl group in (12 beta-/sup 3/H)-labeled deoxycholic acid given to two patients operated with subtotal colectomy and ileostomy was markedly reduced (less than 20% of normal).},
doi = {},
journal = {J. Lipid Res.; (United States)},
number = ,
volume = 2,
place = {United States},
year = {Sat Feb 01 00:00:00 EST 1986},
month = {Sat Feb 01 00:00:00 EST 1986}
}
  • A conjugated bile acid, 23-selena-25-homotaurocholic acid (SeHCAT), labeled with the gamma emitter Se-75, has been evaluated in man. Absorption and excretion were compared with that of simultaneously administered (23-14C)cholic acid. SeHCAT is absorbed quantitatively following oral administration, secreted into the bile at the same rate as cholic acid, reabsorbed from the small intestine, and resecreted. It is not absorbed when the terminal ileum has been excised or bypassed. SeHCAT is therefore the first of a new class of radiopharmaceuticals, namely, gamma-emitting tracers of the complete cycle of the enterohepatic circulation. Its use will simplify investigation of the functional state ofmore » the terminal ileum by eliminating the need to collect and process feces.« less
  • A conjugated bile acid, 23-selena-25-homotaurocholic acid (SeHCAT), labeled with the gamma emitter Se-75, has been evaluated in man. Absorption and excretion were compared with that of simultaneously administered (23-/sup 14/C)cholic acid. SeHCAT is absorbed quantitatively following oral administration, secreted into the bile at the same rate as cholic acid, reabsorbed from the small intestine, and resecreted. It is not absorbed when the terminal ileum has been excised or bypassed. SeHCAT is therefore the first of a new class of radiopharmaceuticals, namely, gamma-emitting tracers of the complete cycle of the enterohepatic circulation. Its use will simplify investigation of the functional statemore » of the terminal ileum by eliminating the need to collect and process feces.« less
  • Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and smallmore » intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.« less
  • Total biliary diversion markedly depressed urinary excretion of I/sup 131/ intravenously administered. The effect was apparent within 2 hr post choledochostomy. Fasting reduced urinary excretion of I/sup 131/ to a minor extent; operative trauma had no effect. Treatment of bile fistula rats with donor bile and/or iodinated drinking water significantly increased I/sup 131/ excretion. I/sup 131/ content of bile was signifi cantly reduced in bile fistula rats only through combined treatment with donor rat bile and iodinated drinking water. I/sup 131/ content in urine paralleled that of sodium under some conditions but not in others. (auth)
  • Four selenium-labeled free bile acids and four selenium-labeled conjugated bile acids, labeled with Se-75 at the C-19, C-22, C-23, or C-24 position, have been synthesized and their absorption and excretion compared with that of (24-14C)cholic acid, following both oral and intravenous administration. All but one of the compounds is absorbed and excreted in bile to a significant extent. One compound, SeHCAT, has been selected for particular study. It is quantitatively absorbed from the gut at the same rate as cholic acid, and both are excreted into the bile at the same rate. It remains almost entirely confined to the enterohepaticmore » circulation (the gut, liver, and biliary tree) and excretion is exclusively fecal. Whole-body retention, measured for 41 days, and tissue distributions suggest that the absorbed radiation dose would be small compared with that in many established tests. Such a compound offers the possibility of a simple, novel, and aesthetically acceptable method of investigating small-bowel disease. It therefore merits further investigation.« less