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)

Diabetes stimulates the functional activity of the intestinal brush border membrane with enhancement of both hydrolytic enzyme activity and membrane transport systems. To determine the mechanism of this effect, we studied the effects of streptozotocin diabetes on the metabolism of one membrane protein, sucrase-isomaltase, which increases its activity in diabetes. The protein was purified and an antiserum prepared. Sucrase-isomaltase from control and diabetic rats was immunologically identical as shown by Ouchterlony double-diffusion analysis of papain-solubilized mucosal proteins. The increase in sucrase enzyme activity in diabetic animals (31.0+/-1.4 U SEM 5 days after streptozotocin vs. 13.1+/-1.0 in controls) was the consequence of increased enzyme protein and not an alteration in catalytic efficiency as demonstrated by quantitative immunoprecipitin reactions. To account for increased sucrase-isomaltase protein in diabetes we studied papain-solubilized mucosal proteins labeled by injection of [(14)C]carbonate and [(14)C]leucine and analyzed incorporation into sucrase-isomaltase protein (anti-serum precipitable) and total protein (trichloroacetic acid precipitable). We found that diabetes did not affect the decay of labeled total protein, but prolonged the decay of labeled sucrase-isomaltase. t((1/2)) of sucrase-isomaltase was 4.4 h in control animals after [(14)C]carbonate injection and 8.8 and 10.2 h, respectively, 2 and 5 days after induction of streptozotocin diabetes. We obtained similar results in experiments with [(14)C]leucine with diabetes increasing t((1/2)) from 6 to 13.6 h. Diabetes did not appear to increase the rate of addition of sucrase-isomaltase to the brush border membrane, since it did not affect the 10- and 60-min incorporations of isotope into sucrase-isomaltase protein relative to incorporation into total protein and did not alter rate constants for synthesis calculated from the t((1/2)) and the change in enzyme mass over time.Thus, enhanced sucrase activity in the diabetic animal is the consequence of an increase in sucrase-isomaltase protein which develops because of a decrease in its rate of degradation.
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PMID:The intestinal brush border membrane in diabetes. Studies of sucrase-isomaltase metabolism in rats with streptozotocin diabetes. 14 62

Exogenously added trypsin arrested invertase secretion by sphacroplasts of Saccharomyces strain 1016. The mechanism of inhibition is presumed due to attack on plasma membrane protein(s). Gross membrane damage by trypsin was not apparent, as evidence by the absence of leakage of intracellular alkaline phosphatase, after trypsin treatment. Trypsin treatment did induce an increased sensitivity to lysis, observed only when changes in osmotic pressure were made and fresh glucose added. While synthesis of invertase was eventually inhibited by trypsin, a greater than twofold increase in internal invertase was observed, due to complete inhibition of secretion. This is the first report of the uncoupling of synthesis and secretion in yeast.
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PMID:Effects of proteolytic enzymes on invertase secretion in sphaeroplasts of Saccharomyces: inhibition by trypsin. 83 55

The vacuolar ATPase of the yeast Saccharomyces cerevisiae acidifies the vacuolar lumen and generates an electrochemical gradient across the vacuole membrane. We have investigated the role of compartment acidification of the vacuolar system in the sorting of vacuolar proteins. Strains with chromosomal disruptions of genes (delta vat) encoding the A (69 x 10(3) M(r)), B (57 x 10(3) M(r)) or c (16 x 10(3) M(r)) subunits of the vacuolar ATPase accumulate and secrete precursor forms of the soluble vacuolar hydrolases carboxypeptidase Y and proteinase A. A kinetic analysis suggests that these precursor proteins accumulate in, and are secreted from, the Golgi complex or post-Golgi vesicles. In addition, subcellular fractionation shows that vacuolar hydrolase-invertase hybrid proteins are inefficiently localized to the vacuole in delta vat strains. This result suggests that the vat mutations cause a steady-state defect in vacuolar protein sorting. The vat mutations also affect the sorting of vacuolar membrane proteins. Precursor forms of alkaline phosphatase are accumulated in vat mutant cells, but to a lesser extent than is seen for the soluble vacuolar hydrolases. This finding, coupled with the insensitivity of alkaline phosphatase to the ATPase inhibitor bafilomycin A1, suggests that vacuolar membrane protein sorting is less sensitive to changes in lumenal pH when compared with the targeting of soluble vacuolar proteins. These results indicate that acidification of the vacuolar system is important for efficient sorting of soluble proteins to the vacuole.
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PMID:Mutations in the yeast vacuolar ATPase result in the mislocalization of vacuolar proteins. 149 Dec 35

We have previously shown that the C-terminal sequence HDEL acts as a retention signal for luminal endoplasmic reticulum (ER) proteins in Saccharomyces cerevisiae, and that it is possible to isolate mutants that fail to retain an invertase fusion protein bearing this signal. Analysis of many such mutants defines two genes, ERD1 and ERD2. Cells lacking the ERD1 gene secrete the endogenous ER protein, BiP. Under normal growth conditions, the rate of secretion is equivalent to the rate at which wild-type cells secrete a modified form of BiP that lacks the HDEL signal altogether. Thus, erd1 cells show a profound disruption of the retention system. The mutant cells have no gross abnormality of their intracellular membrane system, but show defects in the Golgi-dependent modification of glycoproteins. We suggest that sorting of luminal ER proteins normally occurs in the Golgi, and that the function of ERD1 is required for the correct interaction of an HDEL receptor with its ligands. The sequence of ERD1 predicts a membrane protein with several transmembrane domains, a conclusion supported by analysis of ERD1-SUC2 fusion proteins.
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PMID:ERD1, a yeast gene required for the retention of luminal endoplasmic reticulum proteins, affects glycoprotein processing in the Golgi apparatus. 217 21

The effect of methylglyoxal on protein -SH and -NH2 groups in cytosolic and membranous fractions of epithelial cells lining the gastrointestinal tract of rat was investigated, using isolated villus and crypt cells (enterocytes) and colonocytes. It was found that 11-12% cytosolic protein -SH and 14-17% membrane protein -SH groups were lost when villus and crypt cells were treated with 2 mM methylglyoxal. In colonocytes, the corresponding loss in protein -SH groups was 46 and 30% under the same treatment. Similarly, 27-37% protein -NH2 group in the cytosolic fraction and 18-19% protein -NH2 group in membranous fractions of the enterocytes were lost by 2 mM methylglyoxal treatment. In colonocytes, the loss of protein -NH2 group was 30 and 15% in cytosolic and membranous fractions, respectively, under the same treatment. Effect of methylglyoxal on activity of various brush border enzymes such as alkaline phosphatase, gamma-glutamyl transpeptidase, leucine aminopeptidase, Mg2(+)-ATPase, sucrase and lactase was also studied. Alkaline phosphatase and gamma-glutamyl transpeptidase activities were inhibited to the extent of 30 and 15% respectively. There was no significant change in the activities of other enzymes after treating the brush border vesicles with 2 mM methylglyoxal. These findings show that methylglyoxal can cause loss of protein thiol and amino groups and enzyme activity in mucosal cells of rat gastrointestinal tract and the effect is more pronounced in colonocytes, which are in constant contact with bacterial metabolites.
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PMID:Effect of methylglyoxal on protein thiol and amino groups in isolated rat enterocytes and colonocytes and activity of various brush border enzymes. 234 Nov 60

When nuclear localization sequences (termed NLS) are placed at the N terminus of cytochrome c1, a mitochondrial inner membrane protein, the resulting hybrid proteins do not assemble into mitochondria when synthesized in the yeast Saccharomyces cerevisiae. Cells lacking mitochondrial cytochrome c1, but expressing the hybrid NLS-cytochrome c1 proteins, are unable to grow on glycerol since the hybrid proteins are associated primarily with the nucleus. A similar hybrid protein with a mutant NLS is transported to and assembled into the mitochondria. To identify proteins that might be involved in recognition of nuclear localization signals, we isolated conditional-lethal mutants (npl, for nuclear protein localization) that missorted NLS-cytochrome c1 to the mitochondria, allowing growth on glycerol. The gene corresponding to one complementation group (NPL1) encodes a protein with homology to DnaJ, an Escherichia coli heat shock protein. npl1-1 is allelic to sec63, a gene that affects transit of nascent secretory proteins across the endoplasmic reticulum. Rothblatt, J. A., R. J. Deshaies, S. L. Sanders, G. Daum, and R. Schekman. 1989. J. Cell Biol. 109:2641-2652. The npl1 mutants reported here also weakly affect translocation of preprocarboxypeptidaseY across the ER membrane. A normally nuclear hybrid protein containing a NLS fused to invertase and a nucleolar protein are not localized to the nucleus in npl1/sec63 cells at the nonpermissive temperature. Thus, NPL1/SEC63 may act at a very early common step in localization of proteins to the nucleus and the ER. Alternatively, by affecting ER and nuclear envelope assembly, npl1 may indirectly alter assembly of proteins into the nucleus.
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PMID:A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to DnaJ, an Escherichia coli heat shock protein. 255 4

Using a selection for spontaneous mutants that mislocalize a vacuolar carboxypeptidase Y (CPY)-invertase fusion protein to the cell surface, we identified vacuolar protein targeting (vpt) mutants in 25 new vpt complementation groups. Additional alleles in each of the eight previously identified vpt complementation groups (vpt1 through vpt8) were also obtained. Representative alleles from each of the 33 vpt complementation groups (vpt1 through vpt33) were shown to exhibit defects in the sorting and processing of several native vacuolar proteins, including the soluble hydrolases CPY, proteinase A, and proteinase B. Of the 33 complementation groups, 19 were found to contain mutant alleles that led to extreme defects. In these mutants, CPY accumulated in its Golgi complex-modified precursor form which was secreted by the mutant cells. Normal protein secretion appeared to be unaffected in the vpt mutants. The lack of significant leakage of cytosolic markers from the vpt mutant cells indicated that the vacuolar protein-sorting defects associated with these mutants do not result from cell lysis. In addition, the observation that the precursor rather than the mature forms of CPY, proteinase A, proteinase B were secreted from the vpt mutants was consistent with the fact that mislocalization occurred at a stage after Golgi complex-specific modification, but before final vacuolar sorting of these enzymes. Vacuolar membrane protein sorting appeared to be unaffected in the majority of the vpt mutants. However, a subset of the vpt mutants (vpt11, vpt16, vpt18, and vpt33) was found to exhibit defects in the sorting of a vacuolar membrane marker enzyme, alpha-mannosidase. Up to 50% of the alpha-mannosidase enzyme activity was found to be mislocalized to the cell surface in these vpt mutants. Seven of the vpt complementation groups (vpt3, vpt11, vpt15, vpt16, vpt18, vpt29, and vpt33) contained alleles that led to a conditional lethal phenotype; the mutants were temperature sensitive for vegetative cell growth. This temperature-sensitive phenotype has been shown to be recessive and to cosegregate with the vacuolar protein-sorting defect in each case. Tetrad analysis showed that vpt3 mapped to the right arm of chromosome XV and that vpt15 mapped to the right arm of chromosome II. Intercrosses with other mutants that exhibited defects in vacuolar protein sorting or function (vpl, sec, pep, and end mutants) revealed several overlaps among these different sets of genes. Together, these data indicate that more than 50 gene products are involved, directly or indirectly, in the process of vacuolar protein sorting.
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PMID:Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. 306 74

The influence of dietary fatty acid composition on intestinal active and passive transport function, brush border membrane composition, and morphology was examined in rats. Animals fed a semisynthetic diet high in saturated fatty acids demonstrated enhanced in vitro jejunal uptake of decanoic, dodecanoic, palmitic, stearic, and linoleic acid, as well as cholesterol and chenodeoxycholic and taurochenodeoxycholic acid, as compared with uptake in animals fed a semisynthetic diet high in polyunsaturated fatty acids but equivalent in total content of fat and other nutrients, or as compared with Purina chow. Feeding the saturated fatty acid diet was also associated with reduced jejunal uptake of a range of concentrations of glucose, enhanced ileal uptake of leucine, unchanged uptake of galactose, and lower uptake of decanol. The semisynthetic diets did not alter brush border membrane protein, sucrase or alkaline phosphatase activities, cholesterol, or total phospholipids, although the percentage of jejunal amine phospholipids was higher than in rats fed chow. The morphologic differences between the jejunum and ileum were abolished in animals fed the high polyunsaturated fatty acid diet; in rats fed the high saturated fatty acid diet, there was reduced mean ileal villus height, width, thickness, surface area, cell size, and villus density, as well as reduced mucosal surface area. The changes in jejunal transport were not correlated with the alterations in morphology, unstirred layer resistance, food intake, or body weight gain. It is proposed that small changes in the percentage of total dietary lipids composed of essential and nonessential fatty acids (without concurrent alterations in dietary total fat, carbohydrate, or protein) influence active and passive intestinal transport processes in the rat.
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PMID:Dietary fat selectively alters transport properties of rat jejunum. 394 55

The effect of a single oral dose of pp'DDT (100 mg/kg body wt.) has been studied on the intestinal uptake of certain nutrients and on brush border enzymes in rats. Intestinal uptake of leucine, and phenylalanine was considerably increased but there was no change in the absorption of glucose and alanine in DDT fed rats, compared to controls. The activities of brush border sucrase, alkaline phosphatase and Na+, K+-ATPase were significantly depressed in pesticide treated animals, but leucine aminopeptidase levels remained unaffected under these conditions. Analysis of the chemical composition of the microvillus membranes revealed a considerable enhancement in total lipids, phospholipids and triglyceride contents of the membranes in DDT exposed rats, but membrane protein, sialic acid and cholesterol fractions did not record any change. 1-14C-acetate incorporation into various lipid classes was studied to explain the observed increase in membrane lipids in DDT exposed animals.
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PMID:Effect of a single oral dose of pp'DDT on the absorption of nutrients in vitro and on brush border enzymes in rat intestine. 627 79

In experimental diabetes, a number of intestinal brush-border hydrolases and transport systems are stimulated. In this study, we assessed possible effects of diabetes on the composition and membrane fluidity of rat intestinal brush-border membranes that might correlate with these functional changes. We found similar proportions of lipid and protein in the diabetic and control preparations, although there was a considerable increase in total membrane from the diabetic rats, presumably reflecting mucosal hyperplasia. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane protein revealed an increase in the bands corresponding to sucrase-isomaltase, consistent with an increased enzyme activity of sucrase. Membrane lipid analysis revealed only a decrease in fatty acids of the neutral lipid fraction of diabetics--a change that may well have occurred during membrane preparation. 1-6-Diphenyl-1,3,5-hexatriene fluorescence polarization data, obtained as a function of temperature, was similar for the diabetic and control rats, with a three-phase linear model superior to one- and two-phase linear or quadratic models. The overall composition of the intestinal brush-border membrane, unlike other plasma membranes, appears little affected by experimental diabetes.
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PMID:Intestinal mucosa in diabetic rats: studies of microvillus membrane composition and microviscosity. 662 63


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