Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic proteins may play an important role in the intracellular transport of bile acids in enterocytes. The lithocholate binding properties of cytosolic protein from bovine small intestine were studied. Lithocholate binding was observed in the Y (45-50 kDa), Y' (30-35 kDa), and Z fractions (10-15 kDa) following gel filtration of cytosol. A Y protein with glutathione S-transferase activity (46 kDa) was purified by S-octyl-glutathione affinity chromatography and chromatofocusing (eluted at pH 7.5) of the Y fraction. Two Y' bile acid binding proteins with dihydrodiol dehydrogenase activity were partially purified from the Y' fraction by chromatofocusing and hydroxyapatite-HPLC. The lithocholate binding affinity of Y' protein (Kd < 0.35 microM) was higher than that of Y protein (Kd = 2 microM) and was comparable to that of Z protein (Kd = 0.2 microM). The binding affinity of Y protein was higher for bilirubin (Kd = 2.5 microM) than that for BSP (Kd = 200 microM). This was comparable to the binding affinity of bovine hepatic Y protein. These data indicate that Y' and Z proteins participate in the intracellular transport of bile acids from the brush border to the basolateral pole in enterocytes.
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PMID:Lithocholate binding by Y and Y' proteins in bovine small intestine. 132 60

Dietary animal fat increases the risk of colorectal cancer. A factor in the increased risk is hypothesised to result from the inhibition of isoforms of a colonic epithelial cell enzyme that detoxifies genotoxins, glutathione S-transferase, by one of the major secondary bile acids produced in the colon by fat digestion, lithocholic acid. The inhibition allows mutagens to persist in colonic epithelial cells while proliferation is stimulated by secondary bile acids, with a concomitant greater frequency of neoplasia-associated mutations than when proliferation is stimulated in the absence of the mutagens. Elements in the hypothesis include the ability of relatively low concentrations of lithocholic acid to inhibit isoforms of glutathione S-transferase found in colon epithelial cells, entry of lithocholic acid into the epithelial cells, and the correlation of neoplasia-associated colon pathology with high levels of lithocholic acid in fecal water. Higher pH values in the colonic stream are identified as exacerbating the effects of lithocholic acid by increasing its solubility. Lithocholic acid is suggested to be more inhibitory to glutathione S-transferase than the other major colonic secondary bile acid, deoxycholic acid, on the basis of inhibition-structure relationships.
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PMID:A factor in the increased risk of colorectal cancer due to ingestion of animal fat is inhibition of colon epithelial cell glutathione S-transferase, an enzyme that detoxifies mutagens. 146 Nov 70

Lithocholic acid (LCA) is a potent endogenous vitamin D receptor (VDR) ligand. In cholestasis, LCA levels increase in the liver and intestine. The objective of this study is to test the hypothesis that VDR plays a role in inhibiting cholesterol 7alpha-hydroxylase (CYP7A1) gene expression and bile acid synthesis in human hepatocytes. Immunoblot analysis has detected VDR proteins in the nucleus of the human hepatoma cell line HepG2 and human primary hepatocytes. 1alpha, 25-Dihydroxy-vitamin D(3) or LCA acetate-activated VDR inhibited CYP7A1 mRNA expression and bile acid synthesis, whereas small interfering RNA to VDR completely abrogated VDR inhibition of CYP7A1 mRNA expression in HepG2 cells. Electrophoretic mobility shift assay and mutagenesis analyses have identified the negative VDR response elements that bind VDR/retinoid X receptor alpha in the human CYP7A1 promoter. Mammalian two-hybrid, coimmunoprecipitation, glutathione S-transferase pull-down, and chromatin immunoprecipitation assays show that ligand-activated VDR specifically interacts with hepatocyte nuclear factor 4alpha (HNF4alpha) to block HNF4alpha interaction with coactivators or to compete with HNF4alpha for coactivators or to compete for binding to CYP7A1 chromatin, which results in the inhibition of CYP7A1 gene transcription. This study shows that VDR is expressed in human hepatocytes and may play a critical role in the inhibition of bile acid synthesis, thus protecting liver cells during cholestasis.
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PMID:Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes. 1910 15

N-Acetylcysteine (NAC) conjugates of the five major bile acids occurring in man were synthesized in order to investigate the possible formation in vivo of these conjugates. Upon collision-induced dissociation, structurally informative daughter ions were observed. The transformation of cholyl-adenylate and cholyl-CoA thioester into a N-acetyl-S-(cholyl)cysteine by rat hepatic glutathione S-transferase was confirmed by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry (LC/ESI-MS(2)). Lithocholic acid was administered orally to bile duct-ligated rats that also received NAC intraperitoneally. The NAC conjugate of lithocholic acid was identified in urine by means of LC/ESI-MS(2). Rapid hydrolysis of the BA-NAC conjugates by rabbit liver carboxylesterase was found, demonstrating the possible labile nature of the NAC conjugates formed in the liver.
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PMID:Chemical synthesis of N-acetylcysteine conjugates of bile acids and in vivo formation in cholestatic rats as shown by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry. 1934 70