Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The hydrolysis of glycyl-L-leucine, glycyl-L-tyrosine, tributyrin, sucrose, maltose, soluble starch and alpha- and beta-glycerophosphates by everted segments of rat intestine was estimated separately or in combination. 2. A comparative study showed significant interaction between different substrates which affected their digestion. 3. Two types of interaction were identified: products of hydrolysis (1) affected the hydrolysis of homologous substances, e.g. methionine and alanine inhibited glycyl-L-leucine hydrolysis, maltose reduced glucoamylase (alpha-1,4-glucan glucohydrolase; EC 3-2-1-3) activity (intracatenary interactions); (2) interfered with the hydrolysis of a different group of substances, e.g. tributyrin inhibited dipeptidase (glycyl-L-leucine hydrolase; EC 3-4-3-2) and alkaline phosphatase (EC 3-1-3-1), glycyl-L-leucine interfered with the activity of the latter enzyme (intercatenary interactions). 4. Mechanisms of interactions were suggested by the results of a comparison of the extent of inhibition or activation of two enzymes (glycyl-L-leucine hydrolase and alkaline phosphatase) in situ in everted intestinal segments or after solubilization with papain or Triton X-100, and different treatments known to affect allosteric sites of these enzymes. 5. Tributyrin and dipeptides were found to act on alkaline phosphatase as allosteric regulators. A discontinuity of the Arrhenius plot suggested the existence of different enzyme conformations which were re-arranged by tributyrin. 6. Substrate interactions in digestion were found in adult rat, cat, rabbit and hen. Substantial differences were found between classes (Aves and Mammalia), orders (rodents, lagomorphs and carnivores) and between age-groups within an animal strain (in this instance, for the rat). 7. These interactions are thought to be involved in the co-ordination of digestion with intestinal absorption and to regulate the time and site of subsequent hydrolysis.
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PMID:Substrate interactions on the intestinal mucosa: a concept for the regulation of intestinal digestion. 117 95

Tributyrin (TB) is a prodrug of butyrate known to induce tumor cells to differentiate. We examined its effects on cell growth, viability, cellular morphology and differentiation of HT-29 colon cancer cells in vitro, as reflected by the expression of CEA, E-cadherin and the induction of alkaline phosphatase activity. TB, applied in a stable emulsion, inhibited tumor cell proliferation in a reversible and dose-dependent manner (0.5-4 mM) with significant morphological changes. The IC50 value of TB was 1 mM after 6 days. For comparison, sodium butyrate, applied in equimolar concentration, inhibited cell growth with an IC50 value of 2.2 mM. TB treatment at concentrations of 0.5 mM and 2 mM resulted in an increase of the doubling times by 18% and 160%, respectively, without any effects on cell viability. By a colorimetric immunoassay, 1.5 mM TB induced the expression of both CEA and E-cadherin by about 260% and 100%, respectively. Furthermore, the activity of the brush border enzyme alkaline phosphatase was enhanced in a dose-dependent manner, up to 60-fold at the maximum of 2 mM TB. Our results show that TB is more active than butyrate in suppressing cell growth and concomitantly promoting differentiation of HT-29 colon cancer cells. Hence it may be a promising candidate for clinical therapeutic protocols and merits further investigation.
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PMID:Tributyrin induces growth inhibitory and differentiating effects on HT-29 colon cancer cells in vitro. 982 54

Tributyrin (glyceryl tributyrate, TB) is known to induce malignant cells to differentiate followed by arrest of cell growth and death via apoptosis. We investigated the effects of TB on the distribution of cell cycle phases, differentiation as measured by alkaline phosphatase activity (ALP), and apoptosis of LS 174T colon cancer cells expressed by morphological changes, externalization of phosphatidylserine and stimulation of various caspases. TB (0.6 mM) reduced the proliferation by a 5-fold decrease of tumor cells in the S-phase and 1.3-fold increase in the G2/M-phase of cell cycle after 24 h of incubation. The ALP activity was enhanced in a dose-dependent manner up to 180-fold by 1 mM TB. Apoptosis was seen only above 0.6 mM TB (5-fold increase). Studies with caspase inhibitors revealed that TB mediated cell death was linked to up-regulation of caspases 3 and 8. Our results indicate that TB-induced differentiation promotes apoptosis in LS 174T cells and may explain the mode of action of TB finally resulting in an arrest of tumor cell growth.
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PMID:Tributyrin-induced differentiation promotes apoptosis of LS 174T colon cancer cells in vitro. 1174 64

Butyrate and its prodrug tributyrin, as well as 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), have important physiological effects on proliferation and differentiation in a variety of malignant cells. The aim of this study was to elucidate the role of the vitamin D receptor (VDR) in butyrate-induced cell differentiation and cell cycle arrest in Caco-2 cells, a human colon cancer cell line. Cell differentiation was evaluated by analyzing the activity of alkaline phosphatase (AP). Protein of VDR, cyclins, cyclin-dependent kinases (cdks) and of cdk inhibitors was quantified by Western blot analysis, VDR-mRNA by PCR. Pre- and postconfluent cells were assessed for VDR binding activity. Cell cycle was analyzed by flow cytometry. Tributyrin significantly increased VDR-mRNA level (250% vs. control) and VDR binding activity. Butyrate also enhanced VDR protein content in the nucleus in a time- and dose-dependent manner and more potently than other short-chain fatty acids of a related structure. Both butyrate (640% vs. control) and 1,25-(OH)2D3 (350% vs. control) significantly stimulated differentiation, whereas combined treatment with butyrate and 1,25-(OH)2D3 resulted in a synergistic amplification of AP activity (1400% vs. control). In the presence of the VDR antagonist ZK 191732, butyrate-induced differentiation was completely abolished (150% vs. control). While butyrate alone increased p21Waf1/Cip1 expression and down-regulated cdk 6 and cyclin A, and combined exposure with 1,25-(OH)2D3 resulted in a synergistic enhancement of butyrate-induced changes, expressions did not change from control level after treatment with butyrate and ZK 191732. G1 cell cycle arrest induced by butyrate was also abolished after combined treatment with butyrate and ZK 191732. In conclusion, differentiation and cell cycle arrest of Caco-2 cells induced by butyrate are mediated by up-regulation of VDR, followed by a stimulation of the negative cell cycle regulator p21Waf1/Cip1 and by a down-regulation of cdk 6 and cyclin A, both involved in cell cycle progression.
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PMID:Short-chain fatty acids and colon cancer cells: the vitamin D receptor--butyrate connection. 1289 27