Disease relevance of AGL

• Genetic deficiency of AGL activity causes glycogen storage disease type III (GSD-III) [1].
• A child with GDE deficient in both liver and muscle (GSD-IIIa) had recurrent hypoglycemia, seizures, severe cardiomegaly, and hepatomegaly and died at 4 years of age [2].
• The hyperleukocytic AGL patients which do not have this syndrome are all characterized by a stable or slowly increasing leukocytosis [3].
• (3) Both whole AGL and AGL 1-20 were presented to the patient-derived clones with much higher efficiency by DDR-transfected fibroblasts than by EBV lines [4].
• Glycogenosis type III (Cori disease) is an autosomal recessive disorder caused by the deficiency of the glycogen debranching enzyme, encoded by the AGL gene, and existing in six isoforms alternately spliced in a tissue-specific way [5].

High impact information on AGL

• Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle [6].
• Two had an AG deletion at nucleotides 17 and 18 of the GDE cDNA (17delAG) which resulted in change of subsequent amino acid sequence and a truncated protein (25X); the other had a C to T transition at nucleotide 16 of the cDNA which changed a Glutamine codon to a stop codon (Q6X) [6].
• In the present study, the analysis of the GDE gene in three GSD-IIIb patients by single-strand conformation polymorphism (SSCP), DNA sequencing, restriction analysis, and family studies, revealed each of them as being a compound heterozygote for two different mutations [6].
• Glycogen storage disease type III (glycogen debranching enzyme deficiency): correlation of biochemical defects with myopathy and cardiomyopathy [7].
• cDNA comprising the entire length of the human muscle glycogen debranching enzyme was cloned and its nucleotide sequence determined [8].

Chemical compound and disease context of AGL

• BACKGROUND/AIMS: Glycogen storage disease III (GSD III) is caused by a deficiency of glycogen-debranching enzyme which causes an incomplete glycogenolysis resulting in glycogen accumulation with abnormal structure (short outer chains resembling limit dextrin) in liver and muscle [9].
• In glycogen storage disease type III (glycogen debranching enzyme (DE) deficiency), the activities of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase may be strikingly elevated during childhood but are low during adult life [10].
• Cloning and nucleotide sequence of a gene encoding a glycogen debranching enzyme in the trehalose operon from Arthrobacter sp. Q36 [11].

Biological context of AGL

• Here we report the isolation and nucleotide sequence of liver AGL cDNA and the tissue distribution of the isoform mRNAs [12].
• These results suggest that the human AGL gene contains at least 2 promoter regions that confer differential expression of isoform mRNAs in a tissue-specific manner [1].
• To determine the molecular basis of GSD-III and elucidate the mechanisms for controlling tissue-specific gene expression, we report the isolation and structural organization of the human chromosomal AGL gene [1].
• Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region [1].
• Mutational and haplotype analysis of AGL in patients with glycogen storage disease type III [13].

Anatomical context of AGL

• In this study, we found that a single injection of AGL administered within 2 hours of lethal irradiation resulted in the long-term survival of mice without bone marrow transplantation [14].
• Peripheral blood hematology showed that AGL administration accelerated the recovery of hematopoietic parameters, including reticulocytes and red and white blood cells [14].
• The high frequency of this syndrome during the course of AGL and of acute phase of CGL seems to be linked to the low deformability of the myeloblasts [3].
• In the present report we investigated T cell responses to A-gliadin (AGL), a major alpha-gliadin component known to activate disease [4].
• The 5 HT organelles/volume ratio was normal in AGL and ALL but was significantly decreased in AML [15].

Associations of AGL with chemical compounds

• Thus it is likely that the AMPK-GDE association is a novel mechanism regulating AMPK activity and the resultant fatty acid oxidation and glucose uptake [16].
• Mass spectrometry and a Mascot search revealed this protein to be a glycogen debranching enzyme (GDE) [16].
• The quail glycoprotein order of affinities was: Con A >> WGA = AGL = PA-IlL, while that of the pigeon was: AGL > PA-IL > WGA > Con A = PA-IlL [17].
• AGL itself displayed no colony-stimulating activity, but AGL-stimulated spleen cell-conditioned medium (AGL-SCM) promoted the proliferation and differentiation of bone marrow mononuclear cells from normal mice and Lin marrow cells from 5-fluorouracil (5-FU)-treated mice [14].
• AGL 2592 induces a dose-dependent and time-dependent inhibition of tyrosine phosphorylation of numerous proteins, including Stat3, and an increase of Bcl-2 phosphorylation, both biochemical hallmarks of growth inhibition and apoptosis [18].

Regulatory relationships of AGL

• These findings suggest that AGL may be a useful in treating radiation-induced hematopoietic damage [14].

Other interactions of AGL

• The predominant form of human liver AGL cDNA (isoform 1) contained 400 bp of 5' untranslated region, 4596 bp of coding region, and 2371 bp of 3' untranslated region [12].
• Herein, we describe the identification of a family of PTK inhibitors whose most potent member is AGL 2592 [18].
• 1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart [19].

Analytical, diagnostic and therapeutic context of AGL

• Molecular cloning and nucleotide sequence of cDNA encoding human muscle glycogen debranching enzyme [8].
• While the novel AGL mutation c.1222C>T was not detectable among 198 German newborns, nine out of 272 children from the Faroese neonatal screening program were found to be heterozygous for this mutation [20].
• Our recent identification of three highly informative DNA polymorphic markers in the AGL gene allowed us to perform prenatal diagnosis and carrier detection in two GSD-III families with unknown mutations, using the polymerase chain reaction (PCR) and restriction analysis [21].
• The apparent molecular mass of the lectins, as determined by gel filtration chromatography, was 56 kDa for ACL and 55 kDa for AGL [22].
• Using a randomized cross-over design, one of the two GXTs was preceded by a GDE [23].

References