Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the cyr 1 mutants (cyr 1-2) in yeast produced low levels of adenylate cyclase and cyclic AMP at 25 degrees and was unable to derepress acid phosphatase. Addition of cyclic AMP to the cyr1-2 cultures elevated the level of repressible acid phosphatase activity. The bcy1 mutation, which suppresses the cyr1-2 mutation by allowing activity of a cyclic AMP-independent protein kinase, also allows acid phosphatase synthesis without restoring adenylate cyclase activity. The CYR3 mutant had structurally altered cyclic AMP-dependent protein kinase and was unable to derepress acid phosphatase. The cyr1 locus was different from pho2, pho4 and pho81, which were known to regulate acid phosphatase synthesis. Mutants carrying cyr1-2 and pho80, PHO81c, PHO82 or pho85 mutations, which confer constitutive synthesis of repressible acid phosphatase, produced acid phosphatase. The cyr1-2 mutant produced significantly low levels of invertase and alpha-D-glucosidase. These results indicated that cyclic AMP-dependent protein kinase exerts its function in the synthesis of repressible acid phosphatase and other enzymes.
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PMID:Regulation of repressible acid phosphatase by cyclic AMP in Saccharomyces cerevisiae. 609 Feb 71

The subcellular distribution of adenylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in bloodstream forms of Trypanosoma brucei was determined by isopycnic sucrose-gradient centrifugation of post-large-granule extracts. Cyclic-AMP phosphodiesterase was almost entirely soluble whereas adenylate cyclase was membrane-bound. The latter enzyme appeared to be absent from the plasma-membrane fraction but copurified with acid phosphatase and acid phosphodiesterase indicating a possible association with the flagellar pocket. At least two protein kinase activities could be distinguished as based on their distribution profiles in gradients, their preference for exogenously added acceptor protein and their inhibition and stimulation by suramin and nucleoside, respectively. Suramin-sensitive protein kinase co-purified with the plasma-membrane marker alpha-D-glucosidase and a nucleoside-stimulated protein kinase behaved as a typical cell-sap enzyme. Phosphoprotein phosphatase activity was found to be mainly soluble but a small part seemed to be associated with plasma membranes.
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PMID:Subcellular distribution of adenylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in Trypanosoma brucei. 629 15

Yeast cells with a nonsense adenylate cyclase mutation, cyr1-3, required cyclic AMP for growth. This phenotype was suppressed by the byc1 mutation; however, cyr1-3 bcy1 cells produced no detectable level of adenylate cyclase or cyclic AMP. On induction, the bcy1 and cyr1-3 bcy1 mutant cells produced the same levels of galactokinase and alpha-D-glucosidase as did the wild-type cells and fourfold-higher levels of invertase. Since galactokinase synthesis was severely repressed by glucose in the constitutive GAL81 mutants, irrespective of the cyr1-3 bcy1 genotype, cyclic AMP may not be involved in catabolite repression.
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PMID:Cyclic AMP may not be involved in catabolite repression in Saccharomyces cerevisiae: evidence from mutants unable to synthesize it. 631 23

Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g.. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e.. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
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PMID:Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat. 1038 96

The human ileocaecal adenocarcinoma cell line HCT-8 was characterized for its potential as an in vitro organ-specific model for gastro-intestinal toxicity. HCT-8 cells showed typical epithelial cell morphology, with microvilli and intercellular junctional complexes, and formed domes, consistent with transepithelial fluid secretion. The cells express three intestinal brush-border enzyme activities (alkaline phosphatase, leucine aminopeptidase and alpha-glucosidase), and adenylate cyclase can be stimulated with vasoactive intestinal peptide. The toxicity of eight non-steroidal anti-inflammatory drugs (NSAID; indomethacin, mefenamic acid, ketoprofen, ibuprofen, sulindac, aspirin, phenylbutazone and naproxen) were assessed using the MTT and neutral red uptake assays. The MTT assay was consistently a more sensitive measure of NSAID-induced toxicity, which suggests that perturbation of mitochondrial function may be an early event in NSAID-induced cellular damage. Comparing the rankings observed in acute studies in the rat in vivo with those observed with HCT-8 cells, there are some general agreements. Indomethacin, a potent ulcerogen in vivo, was consistently among the most toxic in vitro, while aspirin and phenylbutazone have comparatively low rankings in vitro and in vivo. In man, with chronic administration, indomethacin is again ranked as a potent ulcerogen, as is aspirin, in contrast to the in vitro data with HCT-8. Therefore, NSAID-induced toxicity in HCT-8 cells assessed by the MTT or neutral red assays, can only partially predict toxicity in vivo, which suggests that local gastro-intestinal environmental factors, such as luminal acidity, may play a role in vivo. The ability of HCT-8 cells to reconstitute intact epithelial layers, thereby allowing such environmental factors to be mimicked, allows further development of these cells as a model for the in vitro prediction of in vivo gastro-intestinal toxicity.
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PMID:Toxic effects of non-steroidal anti-inflammatory drugs in a human intestinal epithelial cell line (HCT-8), as assessed by the MTT and neutral red assays. 2073 14