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

Multigene families are a ubiquitous feature of eukaryotes; however, their presence in Saccharomyces is more limited. The MAL multigene family is comprised of five unlinked loci, MAL1, MAL2, MAL3, MAL4 and MAL6, any one of which is sufficient for yeast to metabolize maltose. A cloned MAL6 locus was used as a probe to facilitate the cloning of the other four functional loci as well as two partially active alleles of MAL1. Each locus could be characterized as a cluster of three genes, MALR (regulatory), MALT (maltose transport or permease) and MALS (structural or maltase), encoded by a total of about 7 kb of DNA; however, homologous sequences at each locus extend beyond the coding regions. Our results indicate that there is extensive homology among the MAL loci, especially within their maltase genes. The greatest sequence diversity occurs in their regulatory gene regions. Southern cross analyses of the cloned MAL loci indicate a single duplication of the MAL6R-homologous sequences upstream of the MAL6R gene as well as an extensive duplication of more than 10 kb at the MAL3 locus. The large repeat at the MAL3 locus results in the presence of four copies of MAL3R-homologous sequences and two copies of MAL3T-homologous sequences at that locus. Two naturally occurring inactive alleles of MAL1 show a deletion or divergence of their MALR sequences. The significance of these repeats in the evolution of the MAL multigene family is discussed.
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PMID:Structure of the multigene family of MAL loci in Saccharomyces. 254 70

Both the MAL1 and MAL6 loci in Saccharomyces strains have been shown by functional and structural studies to comprise a cluster of at least three genes necessary for maltose utilization. They include regulatory, maltose transport and maltase genes designated MALR, MALT and MALS, respectively. Subclones of each gene derived from the MAL6 locus were inserted into the multicopy shuttle plasmid YEp13, introduced into MAL1 and mal1 strains and the effects of altered gene dosage of each gene, or a combination of them, on MAL gene expression investigated. MAL1 strains transformed with a plasmid carrying the MAL6S gene showed coordinate four to five fold increases in both maltase enzyme activity and its mRNA, whereas no increase in maltose transport activity or of MALT mRNA was observed when MAL6T was present on multicopy plasmids. The presence of the MAL6R gene on a multicopy plasmid led to greatly increased transcription of both inducible and constitutive mRNAs with homology to the regulatory gene; it also gave rise to two fold increases in both induced maltase mRNA levels and enzyme activity, but only in the presence of maltose. However, it had no apparent effect on the accumulation of MALT mRNA. Finally, the induction kinetics of plasmid-borne and chromosomal MALS and MALT gene expression were examined under conditions of altered gene dosage of the MAL6 regulatory and structural genes. The results of these experiments indicate that MALR encodes a trans-acting positive activator that requires maltose for induction of MALS and MALT transcription even when the regulatory gene is present on a multicopy plasmid. Maltose transport can be a rate-limiting factor in MAL gene expression, at least in the early stages of induction. The regulation of the MALS and MALT genes, whose activities are coordinately induced in MAL1 strains by maltose, may in fact exhibit some important differences.
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PMID:Regulation of MAL gene expression in yeast: gene dosage effects. 332 27

Maltose utilization in yeast requires the presence of any one of the five unlinked, homologous MAL loci. Transcription of the two structural genes MALT (permease) and MALS (maltase) is induced by maltose and catabolite-repressed by glucose. MAL6T and MAL6S share a common 5' intergenic sequence; deletion studies within this sequence revealed a bi-directionally functioning upstream activation sequence (UASM) consisting of four 11 bp homologous sites. Activation of these sites by the MALR protein results in the coordinate expression of MAL6T and MAL6S. The basal promoter activates MALS expression to a greater extent than MALT and is located in a region that overlaps UASM. Deletion of several subsites within the UASM has an asymmetric effect on MAL gene expression, having a greater affect on MALT than on MALS. Catabolite repression of MAL6T and MAL6S by glucose is controlled at several levels. Using disruption mutants, the positively acting MAL1R protein was also found to play a role in catabolite repression of MAL6T and MAL6S.
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PMID:Shared control of maltose induction and catabolite repression of the MAL structural genes in Saccharomyces. 802 78

Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A and rapamycin, both potent novel immunosuppressants which act on signal transduction pathways in CD4+ T-cells, could potentially modulate immune/inflammatory cellular reactions involved in tissue ischemia/reperfusion injury. We hypothesized that cyclosporine A and rapamycin would preserve mucosal cell function and attenuate inflammatory T-cell-mediated cellular changes associated with small bowel ischemic injury. Forty Sprague-Dawley rats underwent 60 min of gut ischemia by vascular occlusion of the superior mesenteric vessels. Animals were randomized to four groups (n = 10): cyclosporine A (CSA, 5 mg/kg/day SQ), rapamycin (RAP, 2 mg/kg/day SQ), cyclosporine A and rapamycin (C&R), and vehicle given to controls (CON). Following 1 hr of reperfusion, small bowel was harvested for xanthine oxidase (XO, units/mg protein) and maltase (MALT, mM substrate degraded/min/g protein) assays. Blood was obtained from the portal vein for tumor necrosis factor-alpha (TNF-alpha, pg/ml) assay. The results of the study are presented below (mean +/- SEM, *, P < 0.05 versus controls). (Table in text) The results indicate that cyclosporine and rapamycin each play a significant role in attenuating ischemia/reperfusion injury in the gut. These data suggest that there are cytoprotective and anti-inflammatory mechanisms of these drugs independent of T-cell signal transduction that provide some protective effect in small bowel ischemia. Furthermore, T-cell-mediated immune mechanisms may not be associated with the adverse effects of small bowel ischemia/reperfusion injury. Additional investigation will be necessary in order to define the role of T-cell-mediated immune injury in the gut and how this relates to the beneficial effect of immunosuppression in small bowel mucosal ischemic injury.
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PMID:Beneficial effects of cyclosporine and rapamycin in small bowel ischemic injury. 890 56

In Saccharomyces cerevisiae maltose utilization requires a functional MAL locus, each composed of three genes: MALR (gene 3) encoding a regulatory protein, MALT (gene 1) encoding maltose permease and MALS (gene 2) encoding maltase. We show that constitutive activation of the RAS/protein kinase A pathway severely reduces growth of MAL1 strains on maltose. This may be a consequence of reduction in MALT mRNA, reduced Vmax and increased catabolite inactivation of the MALT-encoded maltose transporter in the MAL1 strain. Mutations in the GGS1/TPS1 gene, which restricts glucose influx and possibly affects signalling, relieve carbon catabolite repression on both maltase and maltose permease and reduce maltose permease inactivation.
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PMID:Regulation of maltose utilization in Saccharomyces cerevisiae by genes of the RAS/protein kinase A pathway. 903 5

We have studied four novel MAL promoters isolated from a single strain of bakers' yeast. Within these promoters we have identified up to five tandem 147 bp repeats located between the MAL UAS region and the MALT TATA box. These repeats strongly reduce MALT (maltose permease) gene expression but only weakly reduce MALS (maltase) gene expression. Insertion of the 147 bp elements into the heterologous CYC1 promoter reduced expression when located between the CYC1 UAS and the TATA box, but not when located upstream of the UAS. We propose that these naturally occurring repeats have evolved as a mechanism to lower the level of MALT expression relative of MALS expression, thus avoiding possible toxic effects associated with over-expression from multiple copies of the permease gene.
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PMID:Tandemly repeated 147 bp elements cause structural and functional variation in divergent MAL promoters of Saccharomyces cerevisiae. 930 Oct 20

Maltose utilization and regulation in aspergilli is of great importance for cellular physiology and industrial fermentation processes. In Aspergillus oryzae, maltose utilization requires a functional MAL locus, composed of three genes: MALR encoding a regulatory protein, MALT encoding maltose permease and MALS encoding maltase. Through a comparative genome and transcriptome analysis we show that the MAL regulon system is active in A. oryzae while it is not present in Aspergillus niger. In order to utilize maltose, A. niger requires a different regulatory system that involves the AmyR regulator for glucoamylase (glaA) induction. Analysis of reporter metabolites and subnetworks illustrates the major route of maltose transport and metabolism in A. oryzae. This demonstrates that overall metabolic responses of A. oryzae occur in terms of genes, enzymes and metabolites when the carbon source is altered. Although the knowledge of maltose transport and metabolism is far from being complete in Aspergillus spp., our study not only helps to understand the sugar preference in industrial fermentation processes, but also indicates how maltose affects gene expression and overall metabolism.
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PMID:Genome-wide analysis of maltose utilization and regulation in aspergilli. 1969 4

The objectives of this study were to describe alterations that age and dietary inclusion of direct-fed microbial (DFM) Bacillus subtilis (BS) and a specific essential oil (EO) blend (carvacrol, cinnamaldehyde, cineol, and pepper extract) causes in the activity of digestive enzymes (maltase: MALT; aminopeptidase-N: APN; intestinal alkaline phosphate: IAP) and expression patterns of genes related to transport (oligopeptide transporter gene: SLC15A1; Na+-dependent glucose and galactose transporter gene: SLC5A1; Na+-independent glucose, galactose, and fructose transporter gene: SLC2A2; ATPase, Na+/K+ transporting gene: ATP1A1) and digestion (aminopeptidase-N gene: ANPEP; maltase-glucoamylase gene: MGAM; Sucrase-isomaltase gene: SI) of carbohydrates and proteins in the small intestine of broilers. Also, the objective was to analyze if growth performance of broilers is affected by supplementation (BS and EO blend). Day-old male broiler chicks (n = 1,320) were assigned to 5 treatments. Diets included a basal diet (BD) as a negative control (CON); experimental diets were BD + BS; BD + BS + EO; BD + EO; BD + antibiotic growth promoter (AGP) avilamycin was the positive control. Performance was evaluated between 1 to 42 d. Transcript abundance of transport-related genes and digestion-related genes were assayed by RT-qPCR and determined at d 7, 21, and 42. MALT-, APN-, and IAP-specific activities were determined at d 7, 21, and 42. Broilers fed BS had greater SLC15A1 mRNA abundance compared to CON, while EO and AGP were related to higher activities of IAP and APN. Analysis over time revealed higher abundance of MGAM, SLC2A2, SLC15A1, SLC5A1 and SI mRNA at d 42 when compared to d 7. Activity of IAP decreased after d 7 and activity of MALT increased with age. The current study suggests that age had effect over carbohydrate and protein transport and carbohydrate digestion. The supplementation of BS DFM hade evident effect over protein transport and that the use of EO in the diet enhanced the activities of carbohydrate and protein digestion, reflecting improvement in digestive and transport physiology of birds. Changes performed by BS DFM and EO did not favor performance.
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PMID:Interference of age and supplementation of direct-fed microbial and essential oil in the activity of digestive enzymes and expression of genes related to transport and digestion of carbohydrates and proteins in the small intestine of broilers. 2833 92