Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synergistic effects of dexamethasone (DEX) and thyroxine (T4) on the postnatal maturation of the 13-d-old rodent small intestine has been studied. Previous studies have shown that hydrocortisone and T4 produced a synergistic response in enzyme maturation. However, T4 elevates corticosteroid-binding globulin, which reduces the clearance of hydrocortisone. Thus, the apparent synergy between T4 and hydrocortisone may have been due to increased glucocorticoid availability. DEX, which does not bind to corticosteroid-binding globulin, was given (d8-12) at 25 pmol (i.e. 0.01 micrograms)/g body wt/d as established by a dose-response study in which this dose of DEX induced one third the maximum response in sucrase activity. In this way, synergy with T4 (130 pmol/g body wt/d, i.e. 0.1 micrograms/g body wt/d, d 5-12) could still be observed. Glucoamylase, lactase, acid beta-galactosidase, alkaline phosphatase, and sucrase activities were determined in two regions of the small intestine. Overall, the results for the two hormones administered alone showed intestinal maturation to be not significantly affected in the T4 group and partially stimulated in the DEX group. When combined, DEX + T4 synergistically increased jejunal sucrase, ileal glucoamylase, and duodenal alkaline phosphatase, and lowered ileal acid beta-galactosidase. The striking exceptions to the general pattern were two brush border enzymes that normally decline during intestinal maturation, namely ileal alkaline phosphatase and jejunal and ileal lactase. For these enzymes, DEX alone did not elicit precocious maturation, and there was no evidence for a synergistic interaction of these two hormones. Serum corticosterone concentrations also were measured. When corticosterone concentrations were compared with enzyme activity, no correlation was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synergistic effects of thyroxine and dexamethasone on enzyme ontogeny in rat small intestine. 140 67

Brush border lactase, sucrase and glucoamylase activities were assessed in jejunal mucosal biopsy specimens from 34 children (median age 11 months; range 1.5-38) having protracted diarrhoea with failure to thrive and 8 well nourished children with normal jejunal mucosal histology (median age 10.2 months; range 2-37). All enzymes showed progressive decrease in activity which was directly in relation to increasing degree of mucosal injury (P less than 0.002). Lactase was significantly reduced even in patients with protracted diarrhoea and normal mucosa (P less than 0.05). Glucoamylase and sucrase were significantly reduced only in the presence of mucosal injury (P less than 0.01). Our data suggest that most children with protracted diarrhoea may not tolerate lactose containing feeds and may need lactose-free diets preferably based on starch. A small number of children with protracted diarrhoea, who have severe mucosal injury may not be able to handle even starch and may require diets based on short chain glucose polymers. The findings of this study, need to be corroborated with well-controlled metabolic balance studies.
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PMID:Intestinal glucoamylase & other disaccharidases in children with protracted diarrhoea. 211 15

Studies of intestinal enzyme development and regulation relevant to the human infant require an animal model with a rate of maturation similar to that of the human infant. Hanford miniature pigs were weaned at 3 days of age to a standard swine weaning formula. At 1, 2, 3, 4, 5, and 6 wk of age, duodenal jejunal, and ileal segments were analyzed for protein content and lactase, sucrase, maltase, glucoamylase, and acid beta-galactosidase activities. Protein content of the small intestine changed significantly with age only in the ileum (p less than 0.05). Lactase activity fell significantly with age in all segments of the small intestine (p less than 0.001); activity was highest in the jejunum. Sucrase and maltase activities were present in all segments of the small intestine at 1 wk of age. Sucrase increased significantly (2-fold, p less than 0.02) with age only in the ileum and maltase increased significantly with age in the jejunum (by 50%, p less than 0.05) and the ileum (3-fold, p less than 0.001). Activities were highest in the jejunum. Glucoamylase activity was present at 1 wk of age and showed a small but significant increase with age only in the duodenum (p less than 0.005). Acid beta-galactosidase activity demonstrated small but significant decreases with age in all small intestinal segments. Glucoamylase and acid beta-galactosidase activities were similar in all segments. In the 6-wk-old pigs, activities of all the enzymes tested were similar to those found in young human infants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The miniature pig as an animal model for the study of intestinal enzyme development. 312 4

The physiological mechanisms that regulate epithelial gene expression during enterocyte migration and differentiation are still poorly understood. The present study has used a combination of quantitative in situ hybridisation, immunohistochemistry and enzyme cytochemistry to examine epithelial cell differentiation in rabbit small intestine. We have measured and compared the levels of mRNA and enzyme activity of the enterocyte brush border markers alkaline phosphatase, amino-peptidase N and lactase in normal villus epithelia and in epithelial cells exposed directly to the Peyer's patch immune environment. All three genes appeared to be expressed in parallel, but in each epithelial population examined, the pattern of gene expression was different. The level of these mRNAs was markedly reduced in Peyer's patch-associated epithelia, this being most pronounced in the follicle-associated epithelium, compared with normal villi. The activities of alkaline phosphatase and aminopeptidase N approximated the expression of their genes, whereas additional post-transcriptional events were shown to clearly contribute to the level of lactase activity in these tissues. These findings demonstrate that the reduced brush border hydrolase activity in Peyer's patch tissue that has been observed previously, is due to a down-regulation of epithelial gene expression in this location. These observations have been used to discuss epithelial differentiation in Peyer's patch tissue and the possible role of local immune factors in regulating such events.
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PMID:Selective regulation of epithelial gene expression in rabbit Peyer's patch tissue. 781 61

We tested the effect of dietary fat on the lipid composition and hydrolase activity of jejunal brush border membranes in piglets. Eighteen 5-wk-old piglets were divided into three groups and for 4 wk fed either an unsaturated low fat diet (3.2% corn oil), an unsaturated high fat diet (17.2% corn oil) or a saturated high fat diet (2.2% corn oil + 15% tallow). Brush border membranes were prepared from the jejunal mucosa and analyzed for cholesterol, phospholipid and fatty acids. The activities of sucrase-isomaltase, lactase-phlorizin hydrolase, maltase-glucoamylase, aminopeptidase and alkaline phosphatase were measured. Lactase-phlorizin hydrolase isoforms were immunopurified and separated by SDS-PAGE, and their relative proportions were measured by densitometry. The activities of the disaccharidases and alkaline phosphatase, but not aminopeptidase, were greater in animals fed the saturated high fat diet than in animals fed the unsaturated high fat diet. The fatty acid composition of the membranes generally reflected the composition of the diet. Correlation analysis demonstrated that the phospholipid, fatty acid and cholesterol compositions of the membranes were associated with the differences in brush border hydrolase activity.
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PMID:Jejunal brush border hydrolase activity is higher in tallow-fed pigs than in corn oil-fed pigs. 793 9

To determine the prevalence of short polymers of glucose and starch malabsorption caused by small intestinal glucoamylase deficiency in children with chronic diarrhea, we studied small bowel biopsy specimens from 511 children (aged 1 month to 9 years) with chronic diarrhea evaluated at 54 medical centers. Glucoamylase and disaccharidase (lactase, sucrase, maltase, and palatinase) enzyme assays were performed. Of the 511 children, 15 had glucoamylase deficiency. Six who had significant small intestinal mucosal injury and disaccharidase deficiencies were defined as having secondary glucoamylase deficiency; the other nine patients with normal mucosal morphologic features were defined as having primary glucoamylase deficiency. Secretin tests showed normal pancreatic amylase values for age in all seven children tested. Four of them had abnormal findings on tolerance tests for starch and short polymers of glucose (rise in blood glucose concentration: < 20 mg/dl) and reducing substances in stools, and three of these four had symptoms of intolerance (abdominal distention, flatulence, and diarrhea). All seven patients responded to a starch elimination diet. After reintroduction of a starch diet, diarrhea recurred in four patients; this was alleviated 48 hours after reelimination of starch. We conclude that intestinal glucoamylase deficiency is present in some patients with chronic diarrhea.
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PMID:Small intestinal glucoamylase deficiency and starch malabsorption: a newly recognized alpha-glucosidase deficiency in children. 815 67

Using metabolic labeling techniques in human intestinal epithelial cell lines in tissue culture and in situ hybridization techniques in normal and inflamed (Crohn's) intestine, recent studies have shown that there is synthesis of acute phase proteins in enterocytes. Moreover, these studies have shown that acute phase protein biosynthesis in enterocytes is regulated by inflammatory cytokines in a manner characteristic of the physiologic acute phase response. In the course of these studies it was noticed that one inflammatory cytokine, interleukin-6 (IL-6), mediated selective down-regulation of the enterocyte-specific, differentiation-dependent integral membrane protein sucrase-isomaltase (SI) in the Caco2 intestinal epithelial cell line. In the current study we examined the effect of several other inflammatory cytokines interleukin-1 (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) on synthesis of SI in Caco2 cells, examined the possibility that inflammatory cytokines affect the synthesis of other enterocyte integral membrane proteins using lactase as a prototype, and examined the possibility that SI gene expression was down-regulated in villous enterocytes in vivo during the local inflammatory response of Crohn's disease. The results show that IL-6 and IFN gamma each mediate a decrease and TNF alpha mediates an increase in synthesis of SI in Caco2 cells. The magnitude of down-regulation by IL-6 and IFN gamma is significantly greater than the up-regulation by TNF alpha. IL-1 beta has no effect on synthesis of SI. Synthesis of lactase is not affected by any of the cytokines. There is a marked specific decrease in SI gene expression in villous enterocytes in acutely inflamed Crohn's ileum as compared to adjacent uninflamed ileum and normal ileum. Taken together, these data show that inflammatory cytokines have specific and selective effects on the expression of the brush border hydrolase SI in tissue culture and in vivo and provide evidence for a previously unrecognized mechanism for disaccharidase deficiency in intestinal inflammation.
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PMID:Regulation of sucrase-isomaltase gene expression in human intestinal epithelial cells by inflammatory cytokines. 855 56

Intestinal epithelial brush border hydrolases are important and sensitive enzyme markers of gastrointestinal development and function. Little is know about the mechanisms that regulate the induction of these enzymes during human fetal development, as these events occur primarily in utero. The present work used ectopically grafted human fetal jejunal xenografts (median age,13.3 wk of gestation), maintained in severe-combined immunodeficient mice, to study the differential expression of five different hydrolases after 10 wk of xenotransplantation. The spatio-temporal distribution of brush border alkaline phosphatase, aminopeptidase-N, alpha-glucosidase, lactase-phlorizin hydrolase, and dipeptidyl peptidase IV enzyme activities were measured quantitatively using scanning microdensitometry along the crypt-villus axes of fetal, xenograft, and pediatric (median age, 34 mo) biopsies. Ectopic grafting of fetal jejunum closely recapitulated the development of these enzymes in utero, with alkaline phosphatase, aminopeptidase-N, alpha-glucosidase, and dipeptidyl peptidase IV enzyme activities closely matching the spatio-temporal distribution and levels recorded in pediatric duodenal biopsies. Lactase-phlorizin hydrolase was the only enzyme not to reach values recorded in pediatric brush border membranes, although activities were significantly (5.6-fold) higher than in pretransplanted fetal bowel. Human jejunal xenografts therefore demonstrate an appropriate developmental induction of brush border hydrolase activity and may represent a useful model to study trans-acting factors that promote human epithelial differentiation and function in vivo. Characterization of such agents may be of potential therapeutic use in the treatment of diseases associated with gastrointestinal immaturity, notably necrotizing enterocolitis.
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PMID:Developmental regulation of intestinal epithelial hydrolase activity in human fetal jejunal xenografts maintained in severe-combined immunodeficient mice. 1147 3

The present study analyzed the existence of carbohydrases in camel pancreas compared to some other ruminants. Disaccharidases (maltase, cellobiase, lactase, trehalase and sucrase), glucoamylase and alpha-amylase were detected in pancreas of camel, sheep, cow and buffalo. Enzyme levels in sheep were lower than in the other ruminants. The highest level was detected for alpha-amylase (EC 3.2.1.2). Moderate activity levels were detected for glucoamylase (EC 3.2.1.3) and maltase (EC 3.2.1.20), while other disaccharidases showed very low activity. The results suggested that, in addition to alpha-amylase, glucoamylase and maltase may be synthesized and secreted from pancreas to the small intestine in ruminants. Camel pancreatic glucoamylase was purified and characterized. The purification procedure included glycogen precipitation and chromatography on DEAE-Sepharose and Sepharose 6B. The molecular mass was 58 kDa for native and denatured enzyme using gel filtration and SDS-PAGE, respectively. The enzyme had a pH optimum at 5.5 and a Km of 10 mg starch/mL with more affinity toward potato soluble starch than the other carbohydrates. Glucoamylase had a temperature optimum at 50 degrees C with heat stability up to 30 degrees C. The effect of different cations and inhibitors was examined. The camel pancreatic glucoamylase may possess an essential thiol.
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PMID:Carbohydrases in camel (Camelus dromedarius) pancreas. Purification and characterization of glucoamylase. 1562 12

Human colon adenocarcinoma cells (HT29-ATCC) and the clone HT29-5F7 were cultured under conditions that differentiate cells to a polarized intestinal phenotype. Differentiated cells showed the presence of junctional complexes and intercellular lumina bordered by microvilli. Intestinal brush border hydrolase activities (sucrase, aminopeptidase N, lactase and maltase) were detected mainly in differentiated HT29-ATCC cells compared with the differentiated clone, HT29-5F7. The presence of non-GM1 receptors of Escherichia coli heat-labile enterotoxin (LT-I) on both types of differentiated HT29 cells was indicated by the inability of cholera toxin B subunit to block LT-I binding to the cells. Binding of LT-I to cells, when GM1 was blocked by the cholera toxin B subunit, was characterized by an increased number of LT-I receptors with respect to undifferentiated control cells. Moreover, both types of differentiated cells accumulated higher amounts of cyclic AMP in response to LT-I than undifferentiated cells. Helix pomatia lectin inhibited the binding of LT-I to cells and the subsequent production of cyclic AMP. LT-I recognized blood group A-active glycosphingolipids as functional receptors in both HT29 cell lines and the active pro-sucrase form of the glycoprotein carrying A-blood group activity present in HT29-ATCC cells. These results strongly suggest that LT-I can elicit an enhanced functional response using blood group A-active glycoconjugates as additional receptors on polarized intestinal epithelial cells.
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PMID:Functional interaction of Escherichia coli heat-labile enterotoxin with blood group A-active glycoconjugates from differentiated HT29 cells. 1688 90


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