Comparison of the choleretic properties of bile acids

The choleretic properties of cholic, chenodeoxycholic, and deoxycholic acid and their taurine and glycine conjugates were compared to their ability to form micelles. It has previously been concluded that deoxycholate has the lowest critical micellar concentration; chenodeoxycholate is slightly higher and cholic is much higher. Conjugation with glycine and taurine has little or no effect on the critical micelle concentration. Since the choleretic properties of bile salts are thought to be directly proportional to their osmotic activities, one might suspect that deoxycholic acid would be the least choleretic, chenodeoxycholic slightly more choleretic and cholic much more choleretic, with little difference between the conjugated and unconjugated forms. However, in the present study, cholic, chenodeoxycholic and taurocholic acid produced similar increases in bile flow (450–700 μl/kg) after an equimolar dose (55 μM/kg). Except for the conjugation of deoxycholic acid with taurine, conjugation of these bile acids with glycine or taurine always decreased the choleretic properties of the bile acids. Therefore, it has been concluded that there is not a good correlation between the in vitro osmotic properties of bile acids and their ability to increase bile flow.     

Hepatic uptake and biliary secretion of bile acids in the perfused rat liver.

Hepatic uptake and biliary secretion have been evaluated in the isolated perfused rat liver for cholic, chenodeoxycholic, ursodeoxycholic acid, both free and taurine-conjugated; the physicochemical properties of the bile acids have also been calculated and related to these experimental parameters. Cholic acid disappearance rate from the perfusate was the fastest, followed by that of ursodeoxycholic and chenodeoxycholic; it was also faster for taurine-conjugated bile acids than for their respective unconjugated forms. The recovery in bile was higher for conjugated than for unconjugated bile acids, and among each class, was higher for cholic than for chenodeoxycholic and ursodeoxycholic. The hepatic uptake correlated negatively (r = -0.99) with the bile acid lipophilicity, while the biliary secretion correlated with the solubility of the molecules. These results show the effect of the physicochemical properties of BA on their hepatic handling, at the physiological concentration of BA in the portal blood.     

Urinary bile acid and bile alcohol excretion does not reflect the genetic polymorphism of debrisoquine hydroxylation

Excretion of the major urinary bile alcohol 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24,25- pentol , and of cholic, chenodeoxycholic, deoxycholic and lithocholic acid was measured in 24 h urine collections of 10 extensive and seven poor metabolizers of debrisoquine. There was no significant difference of the excretion of these cholesterol metabolites between the two groups, indicating that cholesterol hydroxylation to bile alcohols and bile acids is probably not controlled by the same genes responsible for the 'debrisoquine-type' hydroxylation polymorphism.     

Hypocholesterolemic effect of bile acid sulfonate analogs in hamsters

We studied the effects of bile acid sulfonate analogs, namely, 3alpha,7alpha,12alpha-trihydroxy-5beta-cholane-24-sulfonate (C-sul), 3alpha,7alpha-dihydroxy-5beta-cholane-24-sulfonate (CDC-sul), and 3alpha,7beta-dihydroxy-5beta-cholane-24-sulfonate (UDC-sul), on serum and liver cholesterol levels, cholesterol 7alpha-hydroxylase activity, and biliary bile acid composition in hamsters fed cholesterol. Of the three analogs studied, UDC-sul slightly but significantly decreased free, esterified, and total cholesterol concentrations in the serum. UDC-sul and CDC-sul reduced liver total cholesterol levels by 25% and 18%, respectively, particularly in the esterified cholesterol fraction. Analysis of biliary bile acids showed the presence of the administered analogs, indicating that sulfonate analogs efficiently participate in enterohepatic cycling. The proportion of cholic acid was increased in all groups fed sulfonate analogs, but the ratio of glycine to taurine conjugated bile acids (G/T) was elevated only in UDC-sul feeding hamsters. There was no significant change in cholesterol 7alpha-hydroxylase activity in hamsters fed C-sul or CDC-sul, while UDC-sul slightly stimulated the enzyme activity compared to the control. The UDC-sul induced decrease in serum and liver cholesterol concentrations may be secondary to enhanced bile acid synthesis. This is supported by the increased cholesterol 7alpha-hydroxylase activity and elevated G/T ratio in biliary bile acids observed following UDC-sul administration.     

Species-specific and age-dependent bile acid composition: aspects on CYP8B and CYP4A subfamilies in bile acid biosynthesis

The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. The primary trihydroxy bile acid in most mammals is cholic acid. Some species produce other important trihydroxy bile acids, for example the adult pig which produce hyocholic acid instead of cholic acid. The position of the third hydroxyl group in cholic acid and hyocholic acid, 12alpha or 6alpha position, respectively, has a profound effect on the hydrophilic-hydrophobic property of the trihydroxy bile acids. The CYP8B subfamily is required for introduction of the 12alpha-hydroxyl group in cholic acid biosynthesis. The enzyme responsible for 6alpha-hydroxylation in hyocholic acid biosynthesis, however, varies among species. This review will discuss, in particular, porcine members of the CYP8B and CYP4A subfamilies because interesting findings regarding members of these subfamilies have recently been recognized in this species. CYP8B1 was for a long time believed to be absent in the pig but was recently found to be expressed in fetal pig liver. The enzyme catalyzing the 6alpha-hydroxylation in hyocholic acid biosynthesis in pig was found to be an atypical member of the CYP4A subfamily, denoted CYP4A21. The review presents bile acid biosynthesis in view of these findings and discusses physiochemical properties and developmental-dependent aspects related cholic acid and hyocholic acid biosynthesis.     

Ionization of unconjugated, glycine- and taurine-conjugated bile acids by electrospray ionization mass spectrometry

We investigated the effect of organic anions as spray liquid additives on the ionization efficiency of unconjugated, glycine-conjugated and taurine-conjugated bile acids under electrospray ionization conditions. Addition of organic acids influenced the ionization efficiency of whole bile acids. Use of a stronger acid reduced the peak intensity of unconjugated and glycine-conjugated bile acids, while the use of TFA, the strongest acid tested, improved the intensity of taurine conjugates. The hydroxyl group at the C-12 position of cholic acid and deoxycholic acid easily underwent intra-molecular hydrogen bonding with the side chain carboxyl group, accelerating the ionization efficiency. This intra-molecular hydrogen bond may also affect the formation of product ions in low energy-CID. The addition of ammonium ions to the spray liquid influenced the ionization of all bile acids, specifically enhancing the ionization efficiency of unconjugated bile acids.     

Altered bile acid metabolism in alloxan diabetic rats

Changes of cholesterol, phospholipid, triglyceride or bile acid levels in serum liver, bile and feces after the treatment with alloxan were examined in Wistar strain male rats. Serum cholesterol, phospholipid and triglyceride levels and liver cholesterol level markedly increased but liver phospholipid and triglyceride levels remained unchanged. The lipid levels in serum very low density and low density lipoproteins were elevated but those in high density lipoprotein were not. Bile flow was not changed but biliary secretion of cholesterol, phospholipid and bile acids markedly increased. Among the biliary bile acid components, cholic acid markedly increased but the amount of chenodeoxycholic acid was similar to that of normal rats. Fecal excretion of deoxycholic acid increased but that of lithocholic and hyodeoxycholic acids decreased, and alpha, beta- and omega-muricholic acids did not change, thus, the total amount of fecal bile acids remained unchanged. Hepatic cholesterol synthesis was markedly depressed, while cholesterol 7 alpha-hydroxylase activity did not change and cytochrome P-450 content was elevated by about 40%. From such evidence, it was apparent that synthesis of cholic acid increased while that of chenodeoxycholic acid decreased and the total amount of bile acids synthesized did not change in the diabetic rats. Furthermore, marked increase of the pool size of cholic acid and hepatic secretion of cholic acid stimulated the absorption of lipids and produced a hyperlipidemia in the diabetic rats.     

Relative inhibitory activity of bile acids against 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced inflammation,and chenodeoxycholic acid inhibition of tumour promotion in mouse skin two‐stage carcinogenesis

Objectives Bile acids are present in Bezoar Bovis and Fel Ursi, traditionally used as antipyretics and antispasmodics. However the anti‐inflammatory activity of individual bile acids and related compounds has not yet been investigated. In this paper, we report the structure–activity relationships influencing the anti‐inflammatory activity of a variety of structurally different bile acid derivatives and also the inhibitory activity of chenodeoxy‐cholic acid against tumour promotion. Methods Fifty derivatives of bile acids were examined for their inhibitory activity against the induction of oedema in mouse ear by application of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Also, the effect of chenodeoxycholic acid was studied in mouse skin in which tumours had been induced by topical application of 7,12‐dimethylbenz[a]anthracene (DMBA) and promoted by TPA. Key findings Many bile acid derivatives had an inhibitory effect against TPA‐induced ear oedema at a similar grade to that of indometacin. Chenodeoxycholic acid, methyl 3α,7α,15α‐trihydroxy‐5β‐cholan‐24‐oate and methyl 3α,7α,15β‐trihydroxy‐5β‐cholan‐24‐oate showed the most potent activity with an ID50 value of 71–110 nmol/ear, a level corresponding to that of hydrocortisone (69 nmol/ear). Furthermore, chenodeoxycholic acid markedly suppressed tumour‐promoting activity by TPA following initiation by DMBA in mouse skin. Conclusions This is the first report on the anti‐inflammatory activity of bile acids on TPA‐induced inflammatory ear oedema in mice. Chenodeoxycholic acid, methyl 3α,7α,15α‐trihydroxy‐5β‐cholan‐24‐oate and methyl 3α,7α,15β‐trihydroxy‐5β‐cholan‐24‐oate showed the most potent activity, at a level corresponding to that of hydrocortisone. Furthermore, chenodeoxycholic acid markedly inhibited tumour promotion in a two‐stage carcinogenesis model in mouse skin.     

Quantitative relationship between bile acid structure and biliary lipid secretion in rats

A series of unconjugated and taurine conjugated bile acids (BAs) differing in water solubility (SWo), critical micellar concentration (CMC), and hydrophilicity (K') were infused iv to rats at a tracer dose and a dose of 6 mumol/min/kg over a 1-h period. Bile was collected for 3 h to evaluate the role of BA structure on cholesterol, phospholipids secretions, and bile flow. The BAs studied differ in the number (2-3), position (-3, -6, -7, -12), and orientation of the hydroxyls (alpha/beta); the side chain structure was modified by shortening (C-23, nor-BA) and by lengthening (C-25, homo-BA), while maintaining the same structure of nuclear hydroxyls (3 alpha 7 beta). At a "tracer" dose, all C-24 natural BAs are efficiently recovered in bile when administered in both unconjugated and taurine conjugated forms. At a "high dose", all taurine conjugated BAs are efficiently recovered in bile (80-100%). However, a variable recovery was observed among unconjugated BAs: trihydroxy BAs are efficiently recovered (85-100%), while dihydroxy BAs are only partially recovered (25-40%). The side chain-modified BAs [i.e., C-23 nor and C-25 homo analogs of ursodeoxycholic acid (UDCA)] are partially recovered at a tracer dose (20-30%), but less at a high dose (10-20%) when administered in the unconjugated form. In contrast, the corresponding taurine conjugates are more efficiently recovered in bile (60-80%). Conjugation with taurine increases total recovery of unconjugated BAs in bile by not more than 30-40%. Highly hydrophilic and water-soluble BAs, such as ursocholic acid (SWo = 1.67 mM) and cholic acid (SWo = 0.27 mM), can also be secreted as unconjugates, and this accounts for their complete recovery. The conjugation step is rate limiting for poorly soluble BAs such as ursodeoxycholic acid (SWo = 0.009 mM) when administered at a high dose, and critical for nor and homo analogs which are poorly soluble and whose side chain modification partially suppresses their conjugation with taurine or glycine and thereby induces alternative pathways such as glucuronidation or sulfation. The induced bile flow is directly related to the hydrophilicity of the natural C-24 bile acid.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mesophase formation during cholesterol gallstone dissolution in human bile: effect of bile acid composition

Duodenal bile obtained from patients with gallstones who were acutely infused with chenodeoxycholic acid, ursodeoxycholic acid, or cholic acid were examined for the propensity toward the formation of a liquid crystalline mesomorphic phase when cholesterol gallstones were incubated in these bile acids. Bile taken from patients infused with ursodeoxycholic acid was found to be enriched in ursodeoxycholic acid; mesophase formation was detected in these samples but not in bile from patients infused with chenodeoxycholic acid or cholic acid.     

Bile acids increase intracellular Ca(2+) concentration and nitric oxide production in vascular endothelial cells

The effects of bile acids on intracellular Ca(2+) concentration [Ca(2+)](i) and nitric oxide production were investigated in vascular endothelial cells. Whole-cell patch clamp techniques and fluorescence measurements of [Ca(2+)](i) were applied in vascular endothelial cells obtained from human umbilical and calf aortic endothelial cells. Nitric oxide released was determined by measuring the concentration of NO(2)(-). Deoxycholic acid, chenodeoxycholic acid and the taurine conjugates increased [Ca(2+)](i) concentration-dependently, while cholic acid showed no significant effect. These effects resulted from the first mobilization of Ca(2+) from an inositol 1,4,5-triphosphate (IP(3))-sensitive store, which was released by ATP, then followed by Ca(2+) influx. Both bile acids and ATP induced the activation of Ca(2+)-dependent K(+) current. Oscillations of [Ca(2+)](i) were occasionally monitored with the Ca(2+)-dependent K(+) current in voltage-clamped cells and Ca(2+) measurements of single cells. The intracellular perfusion of heparin completely abolished the ATP effect, but failed to inhibit the bile acid effect. Deoxycholic acid and chenodeoxycholic acid enhanced NO(2)(-) production concentration-dependently, while cholic acid did not enhance it. The bile acids-induced nitric oxide production was suppressed by N(G)-nitro-L-arginine methyl ester, exclusion of extracellular Ca(2+) or N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide hydrochloride (W-7) and calmidazolium, calmodulin inhibitors. These results provide novel evidence showing that bile acids increase [Ca(2+)](i) and subsequently nitric oxide production in vascular endothelial cells. The nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in liver diseases including cirrhosis.     

Cholic acid and ursodeoxycholic acid therapy in primary biliary cirrhosis

Summary We treated 6 patients with Stage II primary biliary cirrhosis with cholic acid (CA) 10 mg · kg^–1 per day for 3 months and then with the same dose of ursodeoxycholic acid (UDCA). A matching group of 6 patients was observed for 3 months without any therapy. Liver function tests and serum and stool bile acids were investigated before, during and at the end of CA and UDCA therapy.The results of liver function tests deteriorated after 6–8 weeks of CA therapy and the changes were correlated (r=0.92) with an increase in -dihydroxy-bile acids (chenodeoxycholic acid and deoxycholic acid) in the serum. The 24 h excretion of DCA in 24 h faeces was markedly increased.Ursodeoxycholic acid treatment improved liver function tests; after 4 weeks glutamate dehydrogenase (GLDH) had decreased. After 8–12 weeks of therapy ursodeoxycholic acid had increased to 50–60% of the total serum bile acids whereas the more apolar bile acids were significantly decreased. No changes in liver function tests or bile acid metabolism were found in the untreated group.Since CA and UDCA are non-toxic in man, this trial indicates that the apolar bile acids chenodeoxycholic acid and deoxycholic acid may be responsible for the deterioration of liver function in primary biliary cirrhosis. However, the therapeutic effect of UDCA cannot be explained merely by the decrease in -dihydroxy-bile acids in the serum, since the laboratory results had improved prior to the decrease in the serum apolar bile acids.     

Influence of various bile acids on the metabolism of glycyrrhizin and glycyrrhetic acid by Ruminococcus sp. PO1-3 of human intestinal bacteria.

Ruminococcus sp. PO1-3, an intestinal bacterium isolated from human feces, metabolized glycyrrhizin (GL) to glycyrrhetic acid (GA) and GA to 3-oxo-glycyrrhetic acid (3-oxo-GA) and possessed GL beta-D-glucuronidase and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) involved in the metabolism of GL. This bacterial growth was enhanced by GL at a concentration of 0.4 mm and was suppressed by GA at concentration of 1.0 mM. Chenodeoxycholic acid, deoxycholic acid and lithocholic acid among the bile acids added to this bacterium suppressed the growth and GL beta-D-glucuronidase activity and 3beta-HSD activity incident to it at a concentration of 1.0 mM, while cholic acid, hyodeoxycholic acid and glycine and taurin conjugates of cholic acid, chenodeoxycholic acid, deoxycholic acid and lithocholic acid had almost no effect on this bacterium at a concentration of 0.2 to 1.0 mm. However, these enzyme activities of this sonicated bacteria were inhibited by all of these bile acids. Although each bile acid and GL added to bacteria at the same time suppressed the growth and the amount of metabolite GA by all bile acids used except cholic acid, taurocholic acid and taurodeoxycholic acid with GL, a combination of each bile acid and GA eased the growth inhibition caused by GA at a concentration of 0.2 mM and enhanced the amount of metabolite 3-oxo-GA by the glycine conjugate of bile acids with GA. GL or GA added after 6 h culture with each of these bile acids and bacteria was metabolized to a relatively large amount of GA by chenodeoxycholic acid and lithocholic acid and their glycine and taurine conjugates, glycocholic acid and taurodeoxycholic acid, or had almost no effect on the amount of metabolite 3-oxo-GA, respectively. These results showed that although GL added after the exposure to bile acid and GA and bile acid added at the same time as bacteria had different bile acid action, these conditions enhanced the amount of metabolite GA from GL and metabolite 3-oxo-GA from GA.     

Effect of bile acids on the binding of drugs and dyes to human albumin

Chenodeoxycholic, cholic, deoxycholic and taurodeoxycholic acids were found to inhibit the binding of 2-(4'-hydroxybenzeneazo)benzoic acid, methyl orange, sulphadimethoxine and warfarin to human albumin. In addition, glycodeoxycholic acid inhibited the binding of sulphadimethoxine and warfarin. In contrast, these bile acids did not inhibit the binding of phenylbutazone. The extent of displacement was in the rank order of: dihydroxy acids (chenodeoxycholic and deoxycholic) greater than trihydroxy acid (cholic) greater than conjugates (glycodeoxycholic and taurodeoxycholic). Thus the introduction of polar groups into the steroid nucleus of bile acids reduces their effectiveness as binding inhibitors. Displacement was usually accompanied by a decrease in the apparent association constant which suggests that the mechanism of displacement may be competitive.     

Correlation of biliary cholesterol, phospholipids and bile acid compositions and the development of cholesterol cholelithiasis in mice

A study was attempted to establish a screening method for detecting cholelitholytic ingredients from a wide variety of natural substances. Although mice were selected as a suitable pathological model of cholelithiasis to detect a small amount of the ingredients, all the conventional lithogenic diets caused unfavorable influence on the animals. Therefore, as the first step we formulated a new lithogenic diet consisting of butter, cholesterol, cholic acid, etc, which was adequate for mice. Subsequently, the pathological characteristics and persistence of cholelithiasis were examined in the animals; the changes in bile compositions including free and conjugated bile acids, cholesterol and phospholipids were observed before and at the onset of cholelithiasis. Following confirmation of the stone formation, a normal diet was substituted for the lithogenic diet to likewise assess the bile compositions 4 and 6 weeks later. An increasing tendency for deoxycholic acid, disappearance of chenodeoxycholic acid and decrease in ursodeoxycholic acid were seen under the condition of cholelithiasis. In addition, the cholic acid-glycine conjugate which should not exist in the normal state and the increase in free and tauring-conjugated cholic acid were noticed. The biliary cholesterol level in treated mice increased to about 4 times higher than that in untreated mice, while the biliary phospholipids and total bile acids levels increased to only about 1.5 and about 2 times the control levels, respectively. The incidence of stone formation rose sharply at an experimental period between 2 and 3 weeks after starting the lithogenic diet. Gallstones die not disappear even at the 6th week after substituting a normal diet for the lithogenic one. However, the cholic acid-glycine conjugate disappeared, and deoxycholic acid as well as chenodeoxycholic acid and ursodeoxycholic acid tended to recover to the normal levels in the bile.     

赤芝子实体中灵芝酸类成分的研究

自赤芝［Ｇａｎｏｄｅｒｍａｌｕｃｉｄｕｍ（Ｆｒ．）Ｋａｒｓｔ．］子实体的二氯甲烷提取物中分离得到一个新的四环三萜化合物，命名为灵芝酸ＤＭ（ｇａｎｏｄｅｒｉｃａｃｉｄＤＭ，Ｉ）。根据光谱（ＵＶ，ＩＲ，１ＨＮＭＲ，１３ＣＮＭＲ，ＭＳ２ＤＮＭＲ）分析，确定其结构为Ｉ式。同时还分离得到二个已知的灵芝酸类化合物，即灵芝酸Ａ（ｇａｎｏｄｅｒｉｃａｃｉｄＡ，Ｉ）和灵芝酸Ｃ（ｇａｎｏｄｅｒｉｃａｃｉｄＣ，ＩＩ）。     

Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity.

A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic conditions in the presence of the title compounds at a dose of 10 micrograms/mL, and the biotransformation of cholic acid into radiolabeled deoxycholic acid and other metabolites was followed by TLC-radiochromatography. Of the compounds studied, 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-N-methylamine showed the highest activity. This compound was used for the in vivo studies and was shown to inhibit the formation of endogenous secondary bile acids when chronically administered to rats at a dose of 60 micrograms/day for 15 days. The treated rats showed an increased ratio of taurocholic acid (primary bile acid) to taurodeoxycholic acid (secondary bile acid) in bile, a fact further suggesting a potent antibacterial activity of the compound toward bacteria responsible for bile acid metabolism.     

19F NMR spectrometry evidence for bile acid conjugates of alpha-fluoro-beta-alanine as the main biliary metabolites of antineoplastic fluoropyrimidines in humans

The human biliary excretion of antineoplastic fluoropyrimidines was studied using 19F NMR. This method allows a direct detection of all the fluorinated metabolites of a fluorinated drug and requires no labeled compound. From a patient with an external bile derivation, treated with 5'-deoxy-5-fluorouridine (5'dFUrd), the biliary excretion of 5'dFUrd metabolites was low (0.8% of the injected dose) and made up of alpha-fluoro-beta-alanine (FBAL) and fluoride ion (F-) which represented approximately equal to 10% of the excreted metabolites and approximately equal to 90% of unknown metabolites. These unknown metabolites were conjugates of FBAL with the two "primary" bile acids only present in the bile of patients with an external bile drainage, i.e. cholic and chenodeoxycholic acids, in a 3:1 ratio. In the bile obtained at surgery from a patient treated with intrahepatic 5-fluorouracil, the major metabolites were conjugates of FBAL with the three major bile acids of human bile, i.e. cholic, deoxycholic, and chenodeoxycholic acids. Moreover, 19F NMR showed that only one of the two diastereoisomers of each conjugate of FBAL with bile acids was formed in vivo, confirming that metabolic FBAL is optically active.     

Biosynthesis of bile acids in mammalian liver.

The biosynthesis of bile acids in mammalian liver and its regulation, together with the physiological role of bile acids, are reviewed in this article. Bile acids are biosynthesized from cholesterol in hepatocytes. Several steps are involved including epimerisation of the 3beta-hydroxyl group, reduction of the delta4 double bond to the 5beta-H structural arrangement, introduction of alpha-hydroxyl groups at C7 or C7 and C12 and, finally, oxidative degradation of the side chain by three carbon atoms. This gives the primary bile acids, cholic and chenodeoxycholic acids. Cholesterol-7alpha-hydroxylation is the rate determining step in the biosynthesis of cholic and chenodeoxycholic acids. Feedback regulation of cholesterol biosynthesis occurs by various mechanisms including termination of the synthesis of specific cytochromes P-450, modulation of specific cytosol proteins, short-term changes in the process of phosphorylation-dephosphorylation and changes in the capacity of the cholesterol pool as a substrate. Prior to being exported from the liver, bile acids are conjugated with glycine and taurine to produce the bile salts. After excretion into the intestinal tract, primary bile acids are partly converted to secondary bile acids, deoxycholic and lithocholic acids, by intestinal microorganisms. The majority of bile acids is absorbed from the intestinal tract and returned to the liver via the portal blood, so that only a small fraction is excreted in the feces. Bile acids returned to the liver can be reconjugated and reexcreted into the bile in the process of enterohepatic recycling. In addition to the physiological function of emulsifying lipids in the intestinal tract, bile acids are particularly important in respect of their ability to dissolve and transport cholesterol in the bile.     

蟒蛇胆化学成分研究

从蟒蛇(Python molurus bivittatus Schlegel)胆中,用柱色谱方法提取分离了化合物Ⅰ和Ⅱ。其中Ⅰ为牛磺去氧胆酸钠。化合物Ⅱ,经元素分析及光谱(IR,¹HNMR,¹³CNMR,¹³C-¹H COSY和MS)分析和化学反应,证明是一个新的化台物,命名为牛磺蟒胆酸钠。