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)

Glutamine is the major fuel for enterocytes and prevents mucosal atrophy in certain animal models. Previous studies in our laboratory have failed to show a trophic effect of glutamine on the small-bowel mucosa following massive resection when added to a chow diet. However, the complexity of the chow diet might potentially interfere with the adequate evaluation of the trophic effect of a single agent such as glutamine. This study was therefore designed to determine whether the addition of glutamine to an elemental diet would augment mucosal adaptation following massive small intestinal resection in a rat model. Male Sprague-Dawley rats were divided into two dietary groups, one receiving an amino acid-based pediatric elemental diet supplemented with 2% glutamine, and the other receiving the diet supplemented with 2% glucose. One half of the animals in each dietary group received 80% jejunoileal resection, and the remainder were sham operated. Fifteen days postsurgery, mucosal weight, DNA, protein, and sucrase activities were determined in both the proximal and the distal small intestine. While both groups of resected animals developed marked increases in all parameters of adaptation, the glutamine-supplemented group did not differ from the control diet group in any parameter. The addition of glutamine to an elemental diet had no enhancing effect on intestinal adaptation after bowel resection. These results are similar to those previously observed in our laboratory when glutamine was added to chow diet. The addition of glutamine to an elemental diet cannot be justified on the basis of its trophic effect in animals.
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PMID:Effect of glutamine-supplemented elemental diet on mucosal adaptation following bowel resection in rats. 858 90

Congenital sucrase-isomaltase deficiency is an example of a disease in which mutant phenotypes generate transport-incompetent molecules. Here, we analyze at the molecular level a phenotype of congenital sucrase-isomaltase deficiency in which sucrase-isomaltase (SI) is not transported to the brush border membrane but accumulates as a mannose-rich precursor in the endoplasmic reticulum (ER), ER-Golgi intermediate compartment, and the cis-Golgi, where it is finally degraded. A 6-kb clone containing the full-length cDNA encoding SI was isolated from the patient's intestinal tissue and from normal controls. Sequencing of the cDNA revealed a single mutation, A/C at nucleotide 3298 in the coding region of the sucrase subunit of the enzyme complex. The mutation leads to a substitution of the glutamine residue by a proline at amino acid 1098 (Q1098P). The Q1098P mutation lies in a region that is highly conserved between sucrase and isomaltase from different species and several other structurally and functionally related proteins. This is the first report that characterizes a point mutation in the SI gene that is responsible for the transport incompetence of SI and for its retention between the ER and the Golgi.
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PMID:Congenital sucrase-isomaltase deficiency. Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment. 860 17

The facilitating effect of glucose on free fructose absorption has been suggested to be due to a sucrase-related transport mechanism. In contrast, the conditions influencing the absorption of sorbitol have hardly been investigated. As amino acids promote transcellular water flow, we investigated their effects on the absorption of fructose and sorbitol. We studied 15 healthy children using breath hydrogen tests following the ingestion of fructose and sorbitol, alone and in combination with glucose or amino acids. Similarly, the effect of acarbose pretreatment on sucrose and fructose-glucose absorption was investigated. The inhibition of sucrase isomaltase by acarbose impedes the absorption of sucrose but not of the fructose-glucose mixture. Fructose absorption is enhanced by glucose and by the amino acids L-alanine, L-glutamine, L-phenylalanine, and L-proline. Similarly, the absorption of sorbitol is facilitated by glucose and L-alanine. These results are not in concordance with a sucrase-related fructose-transport system and suggest another mechanism for glucose-induced enhancement of fructose (and sorbitol) absorption. We hypothesize that the absorption of fructose and sorbitol may be stimulated by the increased water flux induced by active absorption of glucose as well as amino acids.
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PMID:Facilitating effect of amino acids on fructose and sorbitol absorption in children. 885 76

A point mutation in the cDNA of human intestinal sucrase-isomaltase has been recently identified in phenotype II of congenital sucrase-isomaltase deficiency. The mutation results in a substitution of glutamine by proline at position 1098 (Q1098P) in the sucrase subunit. Expression of this mutant sucrase-isomaltase cDNA in COS-1 cells results in an accumulation of sucrase-isomaltase in the ER, intermediate compartment and the cis-Golgi cisternae similar to the accumulation in phenotype II intestinal cells. An interesting feature of the Q1098P substitution is its location in a region of the sucrase subunit that shares striking similarities with the isomaltase subunit and other functionally related enzymes, such as human lysosomal acid alpha-glucosidase and Schwanniomyces occidentalis glucoamylase. We speculated that the Q-->P substitution in these highly conserved regions may result in a comparable accumulation. Here we examined this hypothesis using lysosomal alpha-glucosidase as a reporter gene. Mutagenesis of the glutamine residue at position 244 in the homologous region of alpha-glucosidase to proline results in a protein that is neither transported to the lysosomes nor secreted extracellularly but accumulates in the ER, intermediate compartment and cis-Golgi as a mannose-rich polypeptide similar to mutant sucrase-isomaltase in phenotype II. We propose that the Q1098P and Q244P mutations (in sucrase-isomaltase and alpha-glucosidase, respectively) generate structural alterations that are recognized by a control mechanism, operating beyond the ER in the intermediate compartment or cis-Golgi.
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PMID:A mutation in a highly conserved region in brush-border sucrase-isomaltase and lysosomal alpha-glucosidase results in Golgi retention. 909 38

Germinated barley foodstuff (GBF) derived from the aleurone and scutellum fractions of germinated barley was rich in glutamine and low-lignified hemicellulose. The diarrhea caused by ceco-colectomy could be prevented by feeding GBF to rats. GBF could also increase the protein content and sucrase activity of small intestinal mucosa in this model. This diarrhea-preventive effect of GBF would be based on the water-holding capacity and bulging force under alkaline conditions, e.g. in the small intestine.
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PMID:Effects of germinated barley foodstuff in preventing diarrhea and forming normal feces in ceco-colectomized rats. 953 97

To examine the possibility of active recycling of Emp24p between the endoplasmic reticulum (ER) and the Golgi, we sought to identify transport signal(s) in the carboxyl-terminal region of Emp24p. Reporter molecules were constructed by replacing parts of a control invertase-Wbp1p chimera with those of Emp24p, and their transport rates were assessed. The transport of the reporter was found to be accelerated by the presence of the cytoplasmic domain of Emp24p. Mutational analyses revealed that the two carboxyl-terminal residues, leucine and valine (LV), were necessary and sufficient to accelerate the transport. The acceleration was sequence specific, and the terminal valine appeared to be more important. The LV residues accelerated not only the overall transport to the vacuole but also the ER to cis-Golgi transport, suggesting its function in the ER export. Hence the LV residues are a novel anterograde transport signal. The double-phenylalanine residues did not affect the transport by itself but attenuated the effect of the anterograde transport signal. On the other hand, the transmembrane domain significantly slowed down the ER to cis-Golgi transport and effectively counteracted the anterograde transport signal at this step. It may also take part in the retrieval of the protein, because the overall transport to the vacuole was more evidently slowed down. Consistently, the mutation of a conserved glutamine residue in the transmembrane domain further slowed down the transport in a step after arriving at the cis-Golgi. Taken together, the existence of the anterograde transport signal and the elements that regulate its function support the active recycling of Emp24p.
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PMID:Identification of potential regulatory elements for the transport of Emp24p. 984 83

Yeast invertase contains 14 sequons, all of which are glycosylated to varying degrees except for sequon 5 which is marginally glycosylated, if at all. This sequon overlaps with sequon 4 in a sequence consisting of Asn92-Asn93-Thr94-Ser95(Reddy et al., 1988, J. Biol. Chem., 263, 6978-6985). To determine whether glycosylation at Asn93is sterically hindered by the oligosaccharide on Asn92, the latter amino acid was converted to a glutamine residue by site-directed mutagenesis of the SUC2 gene in a plasmid vector which was expressed in Saccharomyces cerevisiae. A glycopeptide encompassing sequons 3 through 6 was purified from a tryptic digest of the mutagenized invertase and sequenced by Edman degradation, which revealed that Asn93 of sequon 5 contained very little, if any, carbohydrate, despite the elimination of sequon 4. When Ser and Thr were inverted to yield Asn-Asn-Ser-Thr carbohydrate was associated primarily with the second sequon, in agreement with numerous studies indicating that Asn-X-Thr is preferred to Asn-X-Ser as an oligosaccharide acceptor. However, when the invertase overlapping sequons were converted to Asn-Asn-Ser-Ser, both sequons were clearly glycosylated, with the latter sequon predominating. These findings rule out steric hindrance as a factor involved in preventing the glycosylation of sequon 5 in invertase. Comparable results were obtained using an in vitro system with sequon-containing tri- and tetrapeptides acceptors, in addition to larger oligosaccharide acceptors.
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PMID:Glycosylation of the overlapping sequons in yeast external invertase: effect of amino acid variation on site selectivity in vivo and in vitro. 1033 87

Numerous studies indicate beneficial effects of glutamine (Gln) in many models of catabolic adult rats. No data were available for aged rats. The effects of oral L-Gln-enriched diet were tested in endotoxemic 24-mo old rats. First, rats received for 7 d (from d0 to d7) an oral diet supplemented with either L-Gln [1g/(kg. d)] or casein (Cas: isonitrogenous supply) prior to lipopolysaccharide (LPS) challenge. The rats were then killed after 24 h food deprivation (from d7 to d8). Endotoxemia induced a catabolic response as shown by muscle glutamine depletion, hyperphenylalaninemia, small bowel atrophy and impaired functionality and bacterial translocation. The Gln-enriched diet did not prevent muscle Gln depletion but significantly (P </= 0.05) enhanced plantaris protein content by 18% compared to the Cas-LPS rats and reduced the plasma phenylalanine-to-tyrosine ratio (1.32 +/- 0.05 vs. 1.54 +/- 0.10, respectively, P </= 0.01). Gut translocation and histomorphology were unaffected by diet. However, Gln pretreatment reduced the fall in sucrase and glucoamylase activities in the ileum, respectively, by 55 and 63% vs. Cas supplementation (P </= 0.05). In a second study, after endotoxin challenge, healthy 24-mo-old rats were then food-deprived for 2 d (from d0 to d2), received a nonpurified diet for 4 d (from d2 to d6), and then Cas or L-Gln-supplemented diet for 7 d (from d6 to d13). No beneficial effects of Gln supplementation were observed except an increase of 50 and 56% in sucrase and glucoamylase activities in the ileum of Gln-treated rats, (P </= 0.01 vs. healthy rats). In conclusion, the effects of L-Gln supplementation in aged endotoxemic rats were limited.
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PMID:Oral administration of a glutamine-enriched diet before or after endotoxin challenge in aged rats has limited effects. 1049 50

The efficacy of ornithine alpha-ketoglutarate (OKG) in preventing bacterial translocation and dissemination, metabolic disorders and changes in mucosal enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoculation with an Escherichia coli strain (10(10) bacteria/kg body). Two days later, the rats were given either a lipopolysaccharide (LPS) 0127:B8 or a saline injection and were deprived of food for 24 h. Enteral nutrition, [Osmolite, 880 kJ/(kg. d)] supplemented with either OKG (LPS + OKG) or glycine (Saline + Gly or LPS + Gly), was then given for 2 d. Urinary total nitrogen losses and 3-methylhistidine excretion were determined daily. On killing at d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and dissemination to the spleen and liver were evaluated, jejunal mucosa enzyme activities were assayed and tissue free amino acids in muscles were measured. Endotoxin induced translocation from the gut lumen to the MLN in all groups, whereas dissemination occurred only in LPS-treated rats. OKG significantly reduced dissemination of the bacteria in the spleen. 3-Methylhistidine excretion was greater in the LPS + Gly group (+25%, P: < 0.05) than in either the LPS + OKG or Saline + Gly group. The group fed the OKG-enriched diet had higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P: < 0.05). Intestinal sucrase and aminopeptidase activities were higher in the LPS + OKG group than in the LPS + Gly group (-30%, P: < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the prevention of gut-derived sepsis in critically ill patients.
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PMID:Bacterial dissemination and metabolic changes in rats induced by endotoxemia following intestinal E. coli overgrowth are reduced by ornithine alpha-ketoglutarate administration. 1111 Aug 43

There is an overlap of carrier-mediated L-amino acid transport and apparent simple diffusion when measured in intestinal brush border membrane vesicles. Using L-threonine and L-glutamine as representative amino acids, this study was undertaken to estimate apparent simple diffusion of L-amino acids and to establish the effective dosage of HgCl2 for completely blocking carrier-mediated L-amino acid transport in porcine jejunal enterocyte brush border membrane vesicles. Jejunal mucosa was scraped from three pigs weighing 26 kg. Enterocyte brush border membrane vesicles, with an average enrichment of 24-fold in sucrase specific activity, were prepared by Mg2+-precipitation and differential centrifugation. In vitro uptake was measured by the fast filtration manual procedure. HgCl2 blocked the carrier-mediated initial transport of L-threonine and L-glutamine under Na+-gradient condition in a dose-dependent manner. At the minimal concentration of 0.165 micromol HgCl2 mg(-1) protein, carrier-mediated L-threonine and L-glutamine transport was completely inhibited. The apparent L-threonine and L-glutamine diffusion was estimated to be 8.6+/-0.7 and 12.4+/-1.0% of the total uptake at the substrate concentrations of 5 microM (L-threonine) and 50 microM (L-glutamine). Therefore, the treatment of porcine brush border membrane vesicles with a minimum of 0.165 micromol HgCl2 mg(-1) protein completely blocks carrier-mediated L-amino acid transport and enables the direct estimation of apparent L-amino acid diffusion in enterocyte brush border membrane vesicles.
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PMID:Estimation of apparent L-amino acid diffusion in porcine jejunal enterocyte brush border membrane vesicles. 1155 Nov 43


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