Bile acid metabolism

Farnesoid X FXR RXR(DR4) Farnesol, bile acids Bile acid metabolism... 

Shindo et al. [66] treated 19 healthy volunteers with omeprazole 20 mg, cultured gastric and jejunal aspirate, and determined gastric pH and bile acid metabolism. Although motility studies were not performed, it can be assumed that intestinal migrating motor complexes were normal [21] (fig. 4). Bacterial colonization was defined by species density exceeding 105 CFU/0.5 ml, and only reported for those exceeding this limit. 

The consequence of bacterial bile acid metabolism [66, 74,77] is hardly clinically significant malabsorption [6] in otherwise healthy individuals [32,79], but in predisposed individuals this may be different. Accordingly, omeprazole interferes with the absorption of vitamin B12 [80-83] and protein assimilation [84], The mechanism for altered vitamin B12 absorption is prevention of its cleavage from dietary protein [83], for which the importance of the concurrent bacterial overgrowth has not yet been ruled out. 

Shindo K, Machida M, Fukumura M, Koide K, Yamazaki R Omeprazole induces altered bile acid metabolism. Gut 1998 42 266-271. 

Shindo K, Yamazaki R, Koide K, Fukumura M, Hirai Y Alteration of bile acid metabolism by cimetidine in healthy humans. J Investig Med 1996 44 462-469. 

Shindo K, Fukumura M Effect of H2-receptor antagonists on bile acid metabolism. J Investig Med 1995 43 170-177. 

Farnesoid X receptor (FXR) and liver X receptors (LXRs) belong to the same NR family as PXR and CAR. Their primary role lies in cholesterol and bile acid metabolism regulation. Like many NRs of this family, FXR heterodimerizes with RXR in vivo [46]. 

Buhman, K. K., Furumoto, E. J., Donkin, S. S., and Story, J. A. (2000). Dietary psyllium increased expression of ileal apical sodium-dependent bile acid transporter mRNA coordinately with dose-responsive changes in bile acid metabolism in rats. J. Nutr. 130, 2137-2142. 

Romero, A. L., West, K. L., Zern, T., and Eemandez, M. L. (2002). The seeds from Plantago ovata lower plasma lipids by altering hepatic and bile acid metabolism in guinea pigs. /. Nutr. 132, 1194-1198. 

Kliewer, S.A. and Willson, T.M. (2002) Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X... 

Thomas LA, Veysey MJ, Murphy GM, Russell-Jones D, French GL, Wass JAH, Dowling RH. Octreotide induced prolongation of colonic transit increases fecal anaerobic bacteria, bile acid metabolizing enzymes, and serum deoxy-cholic acid in patients with acromegaly. Gut 2005 54 630-5. 

Carr, T.P., Comelison, R.M., Illston, B.J., Stuefer-Powell, C.L., and Gallaher, D.D. 2002. Plant sterols alter bile acid metabolism and reduce cholesterol absorption in hamsters fed a beef-based diet. Nutr. Res. 22, 745-754. 

Bile-acid metabolism explains the ability of certain kinds of dietary fiber to help lower serum cholesterol. A molecule of bile acid circulates through the liver and intestine five or more times before finally being eliminated. Soluble fiber (such as that found in oat bran) binds bile acids, but itself cannot be absorbed. Therefore, fiber-bound bile acids are eliminated in the stool. Because bile acids derive from cholesterol, synthesizing more bile acid drains the body s stores of cholesterol, which leads to a reduction in serum cholesterol, and therefore, to a lower risk of coronary artery disease. Eating oat fiber cannot overcome an excessive dietary cholesterol consumption, of course. In other words, consuming excessive amounts of well-marbled steak and expecting to overcome the effects by eating a bran muffin would be foolish. 

The role of GC-MS in investigations of bile acids follows a closely similar path to other steroids. Their mass spectra have been discussed in detail e.g. [210,211] in addition to their gas chromatographic behaviour. GC-MS in abnormal bile acid metabolism has been reviewed [212] and the investigation of their basic biosynthesis, metabolism [213] and presence in biological fluids in controls [214,215] and diseased states [216] has been reported. 

PFIC 4 This syndrome is caused by a genetically determined 3P-hydroxy-C27-steroid dehydrogenase deficiency, resulting in disturbed bile acid metabolism. There is no... 

Bilirubin metabolism (= jaundice) Bile acid metabolism (= cholestasis) ... 

Genetically induced disorders of bile acid metabolism cause non-obstructive intrahepatic cholestasis. Cholestasis due to primary storage diseases also belongs to this group of disorders, (s. tab. 13.4) see chapter 13)... 

The so-called hormone theory (X Ahlqvist, 1980) is based on the impact of hyperoestrogenaemia on the biliary/canalicular system and bile acid metabolism. The question of sequential causality remains open. (quot. 75)... 

Batta, A.K., Salen, G., Mirchandani, R., Tint, G.S., Shefer, S., Batta, M., Abroon, J., O Brien, C.B., Senior, J.R. Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. Amer. J. Gastroenterol. 1993 88 691 -700... 

Mazzella, G., Parini, P., Bazzoli, F., Villanova, N., Festi, D., Aldini, R., Roda, A., Cipolla, A., Polimeni, C., Tonelli, D., Roda, E Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis. Dig. Dis. Sci. 1993 38 896-902... 

In liver cirrhosis, there are several changes reduction in LCAT (with cholesterol ester fall ), HDL and LDL as well as in VLDL, with a corresponding change in their distribution pattern occurrence of hypertriglycerid-aemia and atypical lipoproteins reduction in phospholipid synthesis (28), possibly with greatly impaired structure and function of the biomembranes. Hepatic extraction of bile acids is reduced with the result that they reach the peripheral circulation - even in the early stages of cirrhosis - and give rise to increased serum values. Bile acids have cholestatic and cytotoxic effects. When bile acid metabolism is markedly compromised, enteral absorption of fat-soluble vitamins is impeded, so that A, D, E and K hypovitaminoses may be observed. 

Hardison, W. G-, and Grundy, S. M. l 83). tffcci of bile acid conjugation pattern on bile acid metabolism in normal humans. GusfrOfMffwtogy 84, 617-620. 

Patteson, T. E., Vlahcevic, Z. R., Schwartz, C. C., Gustafsson, J., Danielsson, H. and Swell, L. (1980). Bile acid metabolism in cirrhosis. VI. Sites of blockage in the bile acid pathways to primary bile acids. Gastroenterology. 79 620-628. 

Willson TM, Jones SA, Moore JT, et al. Chemical genomics Functional analysis of orphan nuclear receptors in the regulation of bile acid metabolism. Med Res Rev 2001 21 513-22. 

Later, Doisy improved the methods used for the isolation and identification of insulin and contributed to the knowledge of antibiotics, blood buffer systems, and bile acid metabolism. 

The regulation of bile acid metabolism is a major function of the liver. Alterations in bile acid metabolism are usually a reflection of liver dysfunction. Cholesterol homeostasis is in large part maintained by the conversion of cholesterol to bile acids and subsequent regulation of bile add metabolism. Bile acids themselves provide surface-active detergent molecules that facilitate both hepatic excretion of cholesterol and solubilization of lipids for intestinal absorption. Bile acid homeostasis requires normal terminal ileum function to absorb bile adds for recirculation (enterohepatic circulation). Alterations in hepatic bile acid synthesis, intracellular metabolism, excretion, intestinal absorption, or plasma extraction are reflected in derangements in bile add metabolism. 

Kinetics of Bile Acid Metabolism. Using an isotope dilution technique, the bile acid pool in normal adults has been found to average from 2 to 4g. Steady state is reached when hepatic synthesis and fecal loss are in balance. In health, the magnitude of each process is 0.3 to 0.8g/day. There are usually 4 to 10 enterohepatic cycles per day. Because of this recycling mechanism, the jejunal concentration of bile acids is maintained at -5 to lOmmol/L during the postprandial state, much higher than the critical micellar concentration of 2mmol/L. Between meals, with decreased entry of bile acids into the intestine, the intraluminal concentration... 

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