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)

Enterocytes are the major epithelial cell type of the small intestine. Their capacity to secret, absorb and digest specific ions and nutrients is dependent on their position along the length of the small intestine as well as their stage of development as they migrate and differentiate along the crypt-villus axis. In order to further understand the molecular processes that regulate enterocyte differentiation and function, this study has compared the levels of six mRNA species produced by genes expressed in rabbit enterocytes; specifically, the multidrug resistance (MDR1) gene encoding the 170-kDa P-glycoprotein, CaBP 9k, which encodes a putative intracellular calcium buffer, calbindin, LPH, APN, and AP which encode the brush-border hydrolases lactase-phlorizin hydrolase, aminopeptidase N and alkaline phosphatase, respectively, and SGLT1, encoding the brush border Na(+)-glucose cotransporter. The level of each mRNA species has been mapped along the small intestine using quantitative in situ hybridisation. This has revealed characteristic regional variations in the abundance of each of the mRNAs, supporting the opinion that there is a strong genetic component to the maintenance of gradients in epithelial function along the length of the small intestine. Analysis of the cellular accumulation of mRNA during enterocyte migration along the crypt-villus axis, over gut-associated lymphoid tissue, and at epithelial boundaries, has, by contrast, established a clear correlation in the expression of these genes. These data illustrate the dynamics of enterocyte gene expression, thereby providing an insight into the molecular mechanisms which co-ordinate the events of cell transformation that underlie functional differences between the epithelial populations of the small intestine.
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PMID:Parallel patterns of cell-specific gene expression during enterocyte differentiation and maturation in the small intestine of the rabbit. 758 2

A number of transmembrane digestive enzymes of the porcine small intestinal brush border membrane were found to be partially Triton X-100-insoluble at 0 degree C and colocalized in gradient centrifugation experiments with the GPI-anchored alkaline phosphatase in low-density, detergent-insoluble complexes commonly known as glycolipid "rafts". Thus, aminopeptidase N (EC 3.4.11.2), aminopeptidase A (EC 3.4.11.7), dipeptidyl peptidase IV (EC 3.4.14.5), and sucrase-isomaltase (EC 3.2.1.48-10) were 34-48% detergent-insoluble. Maltase-glucoamylase (EC 3.2.1.20) was markedly less detergent-insoluble (20%), and lactase-phlorizin hydrolase (EC 3.2.1.23-62) was essentially fully soluble in detergent. In radioactively labeled, mucosal explants, the newly synthesized brush border enzymes began to associate with detergent-insoluble complexes while still in their transient, high mannose-glycosylated form, and their insolubility increased to that of the steady-state level soon after they achieved their mature, complex glycosylation, i.e., after passage through the Golgi complex. Detergent-insoluble complexes isolated by density gradient centrifugation were highly enriched in brush border enzymes, and the enrichment was apparent after only 1 h of labeling, where aminopeptidase N, sucrase-isomaltase, and alkaline phosphatase together comprised 25-30% of the total labeled, detergent-insoluble proteins, showing that sorting of newly made brush border membrane proteins into the glycolipid "rafts" does take place intracellularly. I therefore propose that, in the enterocyte, the brush border enzymes are targeted directly from the trans-Golgi network toward the apical cell surface.
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PMID:Involvement of detergent-insoluble complexes in the intracellular transport of intestinal brush border enzymes. 784 19

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 gain insight into the postnatal growth delay induced by ethanol in utero, we characterized functional impairments of the small intestine of neonatal rats prenatally exposed to ethanol using a well-described model of gestational alcoholism (25% ethanol w/v in the drinking water). Expression of the intestinal enzymes-lactase-phlorizin hydrolase (LPH) and intestinal alkaline phosphatase (IAP)-that are critical for enteral nutrition of neonates was studied. Characteristic patterns of LPH and IAP expression along the proximal-distal (horizontal) and crypt-villus (vertical) axes of the small intestine, as well as the intracellular localization of LPH and IAP mRNAs and immunoreactive proteins within absorptive enterocytes, were not altered by prenatal exposure to ethanol. However, a 10- to 15-fold increase in the number of LPH and IAP mRNA molecules per absorptive enterocyte was found throughout the intestine of ethanol-exposed neonates, compared with controls, whereas lactase and alkaline phosphatase activities per enterocyte remained unchanged. These findings suggest that ethanol in utero alters the mRNA abundance of epithelial enzymes in newborn rat small intestine. Changes in mRNA abundance could be an important aspect of enterocyte adaptation to high ethanol concentrations in gastrointestinal amniotic fluid of ethanol-exposed fetuses.
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PMID:Prenatal ethanol exposure alters the expression of intestinal hydrolase mRNAs in newborn rats. 898 19

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