Physiological basis of alterations in the relative conjugation of bile acids with glycine and taurine

Garbutt, John T.; Lack, Leon; Tyor, Malcolm P.

doi:10.1093/ajcn/24.2.218

Cited by 51 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This results may be explained by the fact that the metabolic steps of hypotaurine to taurine is shorter than those of cysteine to taurine (21), which implies that hypotaurine accumulated in these cells is converted to taurine more rapidly than cysteine. The results obtained in this study coupled with the previously published report that cysteine administrated orally produced an increase in the formation of taurine-conjugated bile acids (31) clearly indicate that the formation of taurine-conjugated bile acids is also maintained by taurine biosynthesized within hepatocytes.…”

Section: Discussionsupporting

confidence: 86%

Roles of Endogenous and Exogenous Taurine and Glycine in the Formation of Conjugated Bi e Acids: Analyses Using Freshly Isolated and Primary Cultured Rat Hepatocytes

Ohkuma

Tamura

Kuriyama

1984

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

Abstract-The regulatory roles of intracellular taurine and glycine, transported and biosynthesized in hepatocytes, on the formation of conjugated bile acids were studied using freshly isolated hepatocytes (fresh hepatocytes) and hepatocytes in primary culture (cultured hepatocytes).Transported taurine significantly increased the rate of taurocholic acid formation both in fresh hepatocytes and cultured hepatocytes.Similarly, the addition of cysteine and hypotaurine, which were metabolically converted to taurine in hepatocytes, facilitated the formation of taurocholic acid in these cells. On the other hand, exogenous glycine into the incubation medium had no effect on the formation of glycocholic acid both in fresh and cultured hepatocytes.In contrast, the addition of serine and threonine, which are metabolically converted to glycine in hepatocytes, significantly increased the formation of glycocholic acid in fresh hepatocytes, although little effect of the additions of serine and threonine on the formation of glycocholic acid was noted in the case of cultured hepatocytes. The present results indicate that the formation of taurine-conjugated bile acids in hepatocytes is maintained by both transported and intracellularly formed taurine in hepatocytes, while that of glycine-conjugated bile acids is regulated by glycine formed within hepatocytes, but not by transported glycine.

show abstract

Section: Discussionsupporting

confidence: 86%

Roles of Endogenous and Exogenous Taurine and Glycine in the Formation of Conjugated Bi e Acids: Analyses Using Freshly Isolated and Primary Cultured Rat Hepatocytes

Ohkuma

Tamura

Kuriyama

1984

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Fasting duodenal bile collected continuously after the injection of unconjugated "C-labeled bile acid, and therefore, before enterohepatic circulation, revealed marked similarity between the G: T ratio of newly conjugated bile acid-"C and the G: T ratio of the total cholate content representative of the circulating bile acid pool. On the basis of similar studies in patients with ileal disorders (29), we have suggested that the elevation in G: T ratio observed is primarily the result of increased hepatic synthesis of conjugated bile acids and a lack of taurine available to the hepatic parenchymal cells leading to preferential conjugation with glycine (30). Others have emphasized the possible contribution of accumulation of glycine conjugates via their greater capacity for transport by passive mechanisms in the absence of ileal function (31)(32).…”

Section: Study Proceduresmentioning

confidence: 87%

Effect of cholestyramine on bile acid metabolism in normal man

Garbutt¹,

Kenney²

1972

J. Clin. Invest.

Self Cite

126

View full text Add to dashboard Cite

A B S T R A C T The effect of cholestyramine administration on the enterohepatic circulation of bile acids was studied in eight normal volunteers. In six subjects the metabolism of sodium taurocholate-'4C was determined after its intravenous injection before and during the 6th wk of cholestyramine administration, 16 g/day. In two subjects, the metabolism of cholic acid-14C was observed before and during the 2nd wk of cholestyramine, 16 g/day. Bile acid sequestration resulted in a more rapid disappearance of the injected primary bile acid and its metabolic products. The composition of fasting bile acids was promptly altered by cholestyramine to predominantly glycine-conjugated trihydroxy bile acid. In four subjects, unconjugated bile acid-14C was administered during cholestyramine administration; the relative proportion of glycine-conjugated bile acid-'C before enterohepatic circulation was similar to the relative proportion of unlabeled glycine-conjugated bile acid present in duodenal contents after an overnight fast, indicating that a hepatic mechanism was responsible for the elevated ratios of glycine-to taurine-conjugated bile acid (G: T ratios) observed. The relative proportions of both dihydroxy bile acids, chenodeoxycholic and deoxycholic, were significantly reduced. Steatorrhea did not occur, and the total bile acid pool size determined after an overnight fast was unaltered by cholestyramine. These findings suggest that in normal man bile acid sequestered from the enterohepatic circulation by cholestyramine is replaced by an increase in hepatic synthesis primarily via the pathway leading to production of glycocholic acid.

show abstract

“…Such therapeutic strategies have been designed for treatment or prevention of relapse of irritable bowel disease or for chemo prevention of cancer. A Western-type diet, with its high meat and fat content, will increase the intestinal BA concentration and, by virtue of its high taurine content, will also increase the percentage of taurine-conjugated BA (8,16). It is estimated that diets rich in taurine-containing food, such as meat and seafood, can raise the amount of taurine-conjugated BA that passes daily through the colon Ͼ10-fold (12).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-κB signal transduction and IL-8 gene expression in colonic epithelial cells

Mühlbauer¹,

Allard²,

Bosserhoff³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Several effects of bile acids (BAs) on colonic epithelial cells (CECs) have been described, including induction of proliferation and apoptosis. Some of these effects are mediated through activation of the NF-κB transcriptional system. In this study, we investigated the molecular mechanisms underlying the BA-induced gene expression in CECs. The human CEC line HT-29 and primary human CECs were treated with dilutions of salts of deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA). NF-κB binding activity was analyzed with EMSA, RelA translocation with immunofluorescence, and IκBα- and RelA-phosphorylation with Western blot analysis. IL-8 mRNA and protein expression were assessed by quantitative PCR and ELISA. Functional impact of NF-κB activation was determined by blocking the proteasome activity with MG132 or by preventing IKK activity with a dominant-negative IKKβ delivered by adenoviral dominant-negative (dn) IKKβ (Ad5dnIKKβ). DCA and TDCA induced IL-8 expression in a dose- and time-dependent manner. It is interesting that DCA but not TDCA induced IκBα-phophorylation, RelA translocation, and NF-κB binding activity. Accordingly, the proteasome inhibitor MG132 blocked DCA- but not TDCA-induced IL-8 gene expression. In contrast, TDCA-induced IL-8 gene expression correlated with enhanced RelA phosphorylation, which was blocked by Ad5dnIKKβ. Our data suggest that DCA-induced signal transduction mainly utilized the IκB degradation and RelA nuclear translocation pathway, whereas TDCA primarily induced IL-8 gene expression through RelA phosphorylation. These differences may have implications for the understanding of the pathophysiology of inflammation and carcinogenesis in the gut.

show abstract

Physiological basis of alterations in the relative conjugation of bile acids with glycine and taurine

Cited by 51 publications

References 24 publications

Roles of Endogenous and Exogenous Taurine and Glycine in the Formation of Conjugated Bi e Acids: Analyses Using Freshly Isolated and Primary Cultured Rat Hepatocytes

Roles of Endogenous and Exogenous Taurine and Glycine in the Formation of Conjugated Bi e Acids: Analyses Using Freshly Isolated and Primary Cultured Rat Hepatocytes

Effect of cholestyramine on bile acid metabolism in normal man

Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-κB signal transduction and IL-8 gene expression in colonic epithelial cells

Contact Info

Product

Resources

About