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Bile Acid Synthesis, Metabolism and Biological Functions

T1 - Stimulation of bile acid synthesis by dibutyryl cyclic AMP in isolated rat hepatocytes

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Bile Acid Synthesis and Utilization

They are partially in theintestine and returned to the liver The portion that is not reabsorbed passesinto the large bowel where they are and metabolized by bacteria into such as lithotomic acid. They are reabsorbed from the colon and returned to theliver but cannot be eliminated from the liver and passes into the blood. Innormal conditions only a minor quantity of bile acids enters the systemic bloodcirculation. Their level increases very early in liver disease.

T1 - Synthesis of [3,4-13C2]-enriched bile salts as NMR probes of protein-ligand interactions

AB - Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of14C-acetate and14C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from14C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with14C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and 224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall incorporation of14C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic acid declined from 55:45 in control cells to 41:59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid synthesis.

Bile salts: definition, function, synthesis from cholesterol

Three [3,4-13C2]-enriched bile salts were synthesized from either deoxycholic or lithocholic acid.

Dietary fibres from fruits, vegetables and cereals have been shown to have cholesterol lowering properties2. In particular, soluble fibre such as pectin from fruit appears to be beneficial. The exact mechanism of action is unknown but evidence suggests that different fibres have slightly different effects. It is likely that soluble fibres are able to increase excretion of bile acids in the faecal matter through binding, alter the ratios of the primary to secondary bile acids, increase faecal cholesterol and fatty acid excretion, as well as having minor indirect effects, such as the replacement of cholesterol containing foods by low cholesterol high fibre alternatives. In addition, some vegetables such garlic and other allium plants, may decrease cholesterol by reduction of hepatic cholesterol synthesis via inhibition of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase. Tocotrienols, the unsaturated forms of vitamin E, may also inhibit HMG-CoA reductase.

The maintenance of the bile salt pool is regulated such that any loss in the faecal matter is compensated for by synthesis in the liver. Because bile salt synthesis requires the use of cholesterol as a substrate, bile salt turnover can contribute to the regulation of cholesterol homeostasis in the body. This may have implications for whole body cholesterol homeostasis through modulation of the cholesterol concentrations in plasma. Bile salt synthesis varies from around 250 mg per day up to nearly 900 mg per day, with the variation resulting from both genetic and environmental factors. Diet may play a role in regulating the synthesis of new bile salts, although exact mechanisms are not fully understood. For example, high fat diets may effect the primary bile salt synthesis rates by inducing an enhanced capacity for primary bile acid re-absorption in the terminal ileum1.

some of the primary bile salts to form “secondary bile acids ..

Bile acids, besides their roles in lipid absorption and cholesterol homeostasis, act also as signaling molecules with systemic effects.

Regulation of bile acid synthesis by an ileal bile acid sensing system. Bile acids are synthesized from cholesterol in the liver. The rate-limiting enzyme in the pathway is cholesterol-7α-hydroxylase (Cyp7a1). Bile acids are secreted across the apical (canalicular) membrane into the bile canaliculus via the Bsep transporter). Bile is then released into the duodenum and flows through the intestinal lumen, where it emulsifies lipids. Lipids are primarily absorbed by enterocytes in the jejunum. The bile acids are transported through the apical Asbt transporter across into ileal enterocytes. Bile acids activate the farnesoid X receptor/retinoid X receptor (FXR/RXR), leading the induction of Fgf15 and Ostαβ. The bile acids are then released into the portal circulation via basolateral Ostα/β and reabsorbed by the hepatic basolateral transporter, Ntcp. binds to the receptor, leading to the repression of Cyp7a1 expression and reduced bile acid synthesis.

Bile acids homeostasis: activation of in the liver promotes several pathways (like the upregulation of the small heterodimer partner-1, ) that lead to the suppression of the Cyp7a1 and of the Cyp8b1, while the efflux from the hepatocyte is increased. signaling may also be involved.

CA and are conjugated to glycine (G) and taurine (T). and are two key enzymes involved in amino conjugation of bile acids.
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  • Bile acids (also called bile salts) ..

    the concentration of bile acids/salts in the small intestine is high ..

  • Conjugated bile salts are strong acids and ..

    The total faecal excretion of bile salts balances hepatic synthesis and ..

  • What Are Bile Acid Synthesis Disorders? - CHOLBAM

    Bile Acid Synthesis - YouTube

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Bile acid analysis in human disorders of bile acid biosynthesis

In the intestine, conjugated CA and are deconjugated and then dehydroxylated at the 7α-position to the secondary bile acids and respectively.

After synthesis of the primary bile acids CA and ..

N2 - Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of14C-acetate and14C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from14C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with14C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and 224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall incorporation of14C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic acid declined from 55:45 in control cells to 41:59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid synthesis.

Bile Salts These are synthesized in ..

Energy expenditure: This work shows that bile acids in mice brown adypocite but also in human skeletal muscle increase energy expenditure by promoting the cAMP-dependent iodothyronine deiodinase type 2 (D2). However this model might not be readily translatable to human: analyzing type 2 diabetic patients, healthy controls and patient with liver cirrhosis no significant correlation between plasma BA and energy expenditure was found

Bile/secretion* Bile Acids and Salts/biosynthesis*

Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of14C-acetate and14C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from14C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with14C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and 224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall incorporation of14C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic acid declined from 55:45 in control cells to 41:59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid synthesis.

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