Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.26 (invertase)
4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suckling rats were given urogastrone-epidermal growth factor (EGF: 1,000 micrograms/kg body weight) or vehicle by gavage at one of three stages of development: 8 to 10, 11 to 13 or 14 to 16 days of age. Intubation was carried out at 8-hourly intervals over these periods. Fourteen to 16 h after the last intubation the rats were killed; that is, at 11, 14 and 17 days respectively. Samples of proximal and distal small intestine (SI) were taken for enzyme analysis. Five enzymes were assayed; sucrase, lactase, gamma-glutamyl transferase, alkaline phosphatase and neutral amino-peptidase, and their activities expressed per g protein. Treatment with EGF had no effect on body weight or on the length of the small intestine at any age. The nature of the effects on enzyme activities depended on the specific enzyme concerned, the site within the small intestine and the timing of the treatment. Lactase was increased by EGF at both sites only on day 14, whereas gamma-glutamyl transferase was increased in proximal samples at 11 and 14 days, and in distal samples at 17 days. Nor was the outcome always to increase activity. On day 11 alkaline phosphatase was increased in proximal SI, but decreased in distal SI; and so too was aminopeptidase N decreased in distal SI at 11 days. Sucrase showed no response at all. The pattern is complex. Certainly it does not indicate accelerated functional maturation.
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PMID:Effects of urogastrone-epidermal growth factor and age at administration on five enzymes in the small intestine of suckling rats. 136 15

Lactase-phlorizin hydrolase was isolated by immunoadsorption chromatography from rabbit brush-border membrane vesicles. Inactivation of the enzyme with [3H]conduritol-B-epoxide, a covalent active site-directed inhibitor, labeled glutamates at positions 1271 and 1747. Glu1271 was assigned to lactase, Glu1747 to phlorizin hydrolase activity. In contrast, the nucleophiles in the active sites of sucrase-isomaltase are aspartates (Asp505 and Asp1394). Asp505 is a part of the isomaltase active site and is localized on the larger subunit, which carries the membrane anchor also, while Asp1394 is a part of the active of sucrase. Alignment of these 2 nucleophilic Glu residues in lactase-phlorizin hydrolase and of their flanking regions with published sequences of several other beta-glycosidases allows the classification of the configuration retaining glycosidases into two major families: the "Asp" and the "Glu" glycosidases, depending on the carboxylate presumed to interact with the putative oxocarbonium ion in the transition state. We offer some predictions as to the Glu acting as the nucleophile in the active site of some glycosidases. By hydrophobic photolabeling, the membrane-spanning domain of lactase-phlorizin hydrolase was directly localized in the carboxyl-terminal region thus confirming this enzyme as a monotopic type I protein (i.e. with Nout-Cin orientation) of the brush-border membranes. A simplified version of the Me2+ precipitation method to efficiently and simply prepare brush-border membrane vesicles is also reported.
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PMID:Location of the two catalytic sites in intestinal lactase-phlorizin hydrolase. Comparison with sucrase-isomaltase and with other glycosidases, the membrane anchor of lactase-phlorizin hydrolase. 138 57

1. Disaccharidase activities of the small-intestinal brush border membrane were studied in six laboratory lines of the house musk shrew, Suncus murinus. 2. Sucrase activity was detected in all shrews of one line, but not in any shrew of three lines. In the other two lines it was found in some shrews, but not in the others. 3. Maltase, isomaltase, trehalase and lactase activities were found in all shrews of all the lines examined. 4. Sucrase was normally associated with isomaltase to form an enzyme complex. 5. Detergent-solubilized isomaltase, whether associated with sucrase or not, was inhibited by antibodies against rabbit sucrase-isomaltase to almost the same extent as the rabbit one, suggesting that isomaltase is not affected by a mutation(s) in sucrase.
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PMID:Intestinal disaccharidases in the house musk shrew, Suncus murinus: occurrence of sucrase deficiency. 145 37

In the rat, starvation lowers jejunal sucrase activity and increases or has no effect upon jejunal lactase activity. The mechanism by which starvation influences these intrinsic microvillus proteins remains unclear. Jejunal sucrase and lactase activities were studied during starvation or refeeding after a three-day fast. Using polyclonal monospecific antibodies, sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH) protein contents were measured in parallel to determine changes in enzyme activation. Sucrase activity and SI protein fell after two and three days of fasting and rose during refeeding. In contrast, lactase activity and jejunal LPH content increased after starvation and decreased after refeeding for 48 hr. For both enzymes, changes in catalytic activity and protein content occurred in parallel. [3H]Leucine incorporation studies in vivo showed more labeling of immunoprecipitable LPH than SI during starvation, but refeeding induced relatively more labeling of SI than of LPH. Therefore, starvation and refeeding produce opposing effects upon jejunal lactase and sucrase activities by modulating LPH and SI protein production and not by modifying enzyme activation.
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PMID:Effects of starvation and refeeding on jejunal disaccharidase activity. 158 86

Sucrase-isomaltase has been used as a marker enzyme to study cell differentiation along the intestinal villus-crypt axis. Previous studies are in agreement that sucrase activity is confined to villus epithelial cells. However, immunoreactivity data are at conflict, with some studies reporting sucrase antigen in crypts as well as villi. To resolve this discrepancy, our goal was to determine the distribution of sucrase-isomaltase mRNA. A cDNA clone representing 3.0 kb of rat sucrase-isomaltase, including the sucrase active site, was characterized. Northern analysis of 12 tissues demonstrated a 6 kb transcript only in the small intestine. Jejunal cell fractions prepared by a washing technique showed declining levels of both sucrase activity and sucrase-isomaltase mRNA as well as increasing levels of thymidine kinase activity from early to later fractions. Since later fractions did not yield pure crypt cells, in situ hybridization using an 35S-labeled sucrase-isomaltase riboprobe was performed. The transition from zero to intense signal at the crypt-villus junction leads us to conclude that in the adult rat, sucrase-isomaltase gene expression is initiated only after cells leave the proliferative cycle and migrate onto the villi.
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PMID:Expression of sucrase-isomaltase mRNA along the villus-crypt axis in the rat small intestine. 161 55

Increased sucrase-isomaltase (SI) expression is a prominent feature of adaptive changes observed in the small intestine of streptozocin-treated chronically diabetic (CD) rats. In this study, we examine the cellular and molecular basis of increased SI expression in CD rats by determining SI specific activities and mRNA abundance in sequentially isolated enterocytes along the villus-to-crypt axis of proximal jejunum and distal ileum. In all regions, two- to fourfold increases in sucrase activity in diabetic rat enterocytes were paralleled by increases in SI mRNA. However, analogous to nondiabetic rat intestine, no differences in SI mRNA abundance were observed between corresponding enterocyte fractions from ileum and jejunum of diabetic rat intestine. By nuclear run-on assays, differences in rates of SI gene transcription were not observed in diabetic and nondiabetic intestinal tissues. We conclude that diabetes induces increased total and specific activities and mRNA abundance of intestinal SI, largely through the stabilization of SI mRNA. Furthermore, analogous to nondiabetic small intestine, differences in proximal-to-distal SI expression appear to be determined at the translational or posttranslational level.
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PMID:Altered regulation of regional sucrase-isomaltase expression in diabetic rat intestine. 161 47

Adenocarcinomas of the colon arise from adenomatous polyps. We hypothesized that sucrase-isomaltase (SI), a glycoprotein hydrolase, found in normal small intestine, fetal colon, and colon carcinomas is a marker associated with progression of adenomatous polyps with dysplasia to adenocarcinomas. To examine this hypothesis, we performed immunostaining using a polyclonal antihuman SI antibody in 32 adenomatous polyps with varying degrees of dysplasia. In addition, sucrase enzyme activity was determined in three sets of simultaneously harvested polyps, cancer, and adjacent normal mucosa from the same patient. All severely dysplastic polyps (6/6) exhibited SI staining. Most polyps (85%) with 3+ staining (i.e., greater than 10% of polyp positive for SI) had severe dysplasia, whereas those with mild dysplasia had either 1% to 5% staining or no staining in 95% of the cases. These data indicate that the extent of SI immunostaining in polyps correlates with the degree of dysplasia (p = 0.0001). Sucrase-isomaltase activity in the polyps was 18.1 +/- 1.8 mU/mg (mean +/- SD); in adjacent carcinoma SI activity was 29.1 +/- 1.8 mU/mg. Adjacent mucosa showed no activity in all cases. In summary, our results suggest that SI expression correlates with the progression of dysplastic adenomatous polyps to carcinoma. Sucrase-isomaltase expression may be useful as a clinical marker to improve our prognostic capabilities in patients with dysplastic lesions of the colon, that is, inflammatory bowel disease.
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PMID:Sucrase-isomaltase: a marker associated with the progression of adenomatous polyps to adenocarcinomas. 169

Adenocarcinoma of the colon is one of the most prevalent and lethal of all human malignancies. The early diagnosis and management of this disease could be improved if biological markers, whose expression was restricted to malignant colon cells, were identified. Sucrase-isomaltase is a glycoprotein hydrolase expressed throughout the small intestine and fetal colon but not in the normal adult colon. This study shows that the expression of enzymatically active sucrase-isomaltase is a ubiquitous property of primary and metastatic colon adenocarcinoma. Significant sucrase enzyme activity (i.e., greater than 5 mU/mg protein) was observed in 16 colon carcinomas but not in adjacent normal colon mucosa. Sucrase-isomaltase messenger RNA was identified in all tumors using reverse transcriptase polymerase chain reaction. Using a quantitative polymerase chain reaction analysis, this study shows that the amount of sucrase-isomaltase messenger RNA in tumors examined (3.4 x 10(-8) to 3.19 x 10(-7) micrograms/micrograms total RNA) was greater than in adjacent mucosa (0 to 3.4 x 10(-8) micrograms/micrograms total RNA). This induction of sucrase-isomaltase messenger RNA and enzyme activity was corroborated by immunostaining. Of 30 colon adenocarcinomas examined, 80% were positive for sucrase-isomaltase. In addition, all colon carcinoma metastases examined were positive for sucrase-isomaltase. The staining pattern was distinct and demarcated tumor cells from the surrounding histologically normal tissue. No sucrase-isomaltase staining was seen in normal mucosa from the same patients. With the exception of lung, no sucrase-isomaltase immunostaining was observed in a variety of examined noncolonic adenocarcinomas. Thus, the specificity and ubiquity of sucrase-isomaltase expression in adenocarcinomas of the colon can be exploited to improve the clinical management of this disease. In addition, studies on the structure of the sucrase-isomaltase gene and its regulatory elements should contribute toward understanding the alteration of gene expression by oncogenic transformation of the colonic mucosa.
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PMID:Expression of enzymatically active sucrase-isomaltase is a ubiquitous property of colon adenocarcinomas. 170 85

Mutations in the sucrase-isomaltase gene can lead to the synthesis of transport-incompetent or functionally altered enzyme in congenital sucrase-isomaltase deficiency (CSID) (Naim, H. Y., J. Roth, E. Sterchi, M. Lentze, P. Milla, J. Schmitz, and H. P. Hauri. J. Clin. Invest. 82:667-679). In this paper we have characterized two novel mutant phenotypes of CSID at the subcellular and protein levels. The first phenotype revealed a sucrase-isomaltase protein that is synthesized as a single chain, mannose-rich polypeptide precursor (pro-SI) and is electrophoretically indistinguishable from pro-SI in normal controls. By contrast to normal controls, however, pro-SI does not undergo terminal glycosylation in the Golgi apparatus. Subcellular localization of pro-SI by immunoelectron microscopy revealed unusual labeling of the molecule in the basolateral membrane and no labeling in the brush border membrane thus indicating that pro-SI is missorted to the basolateral membrane. Mapping of biosynthetically labeled pro-SI with four epitope- and conformation-specific monoclonal antibodies suggested that conformational and/or structural alterations in the pro-SI protein have prevented posttranslational processing of the carbohydrate chains of the mannose-rich precursor and have lead to its missorting to the basolateral membrane. The second phenotype revealed two variants of pro-SI precursors that differ in their content of mannose-rich oligosaccharides. Conversion of these forms to a complex glycosylated polypeptide occurs at a slow rate and is incomplete. Unlike its counterpart in normal controls, pro-SI in this phenotype is intracellularly cleaved. This cleavage produces an isomaltase-like subunit that is transport competent and is correctly sorted to the brush border membrane since it could be localized in the brush border membrane by anti-isomaltase mAb. The sucrase subunit is not transported to the cell surface and is most likely degraded intracellularly. We conclude that structural features in the isomaltase region of pro-SI are required for transport and sorting of the sucrase-isomaltase complex.
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PMID:Naturally occurring mutations in intestinal sucrase-isomaltase provide evidence for the existence of an intracellular sorting signal in the isomaltase subunit. 171 81

Sequence comparison of the primary structure of the yeast Schwanniomyces occidentalis glucoamylase (GAM) with GAMs in different microorganisms did not reveal significant similarities. By contrast, striking similarities were, surprisingly, found with 3 mammalian secretory and integral membrane proteins: the 2 subunits of intestinal brush border sucrase-isomaltase and human lysosomal alpha-glucosidase. The similarities among these proteins are found as clusters of up to 8 amino acids and distributed all over the protein sequences. The major sequence differences are found in the N-terminal regions accounting, probably, for the different cellular locations of these proteins. The high level of similarities between sucrase, isomaltase, Sch. occidentalis GAM and human lysosomal alpha-glucosidase suggest that these proteins are derived from the same ancestral gene. To our knowledge, this is the first report that describes similarities between a yeast secretory protein and mammalian secretory and integral membrane proteins.
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PMID:Striking structural and functional similarities suggest that intestinal sucrase-isomaltase, human lysosomal alpha-glucosidase and Schwanniomyces occidentalis glucoamylase are derived from a common ancestral gene. 174 81


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