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)

1. Albumin activates human liver acid alpha-glucosidase (alpha-D-glucoside hydrolase, EC 3.2.1.20). From the Arrhenius plot, pH-dependence and Lineweaver-Burk plots it can be concluded that this activation is not only due to stabilisation of the enzyme, but also influences the enzymatic activity. It is proposed that for optimal functioning human liver acid alpha-glucosidase needs a protein environment. 2. Glycogen has a competitive inhibitory effect on the hydrolysis of 4-methylumbelliferyl-alpha-D-glucopyranoside, in contrast to maltose which exhibits a non-competitive type of inhibition. It is concluded that two catalytic sites exist, one for glycogen and one for maltose, while both sites influence each other. With glycogen as substrate a break in the Arrhenius plot is found. This is not the case when maltose is used as substrate. 3. The effect of antibody raised against human liver acid alpha-glucosidase on the activity of human liver acid alpha-glucosidase is studied. No corss-reacting material could be demonstrated in the liver of a patient with glycogen storage disease Type II (M. Pompe, acid alpha-glucosidase deficiency).
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PMID:Some properties of human liver acid alpha-glucosidase. 1 57

Tissues from the cerebral cortex, liver and myocardium of a patient with Lafora disease were obtained at autopsy and were studied biochemically. 1. Glucose content in the myocardium and liver was almost nil while that in the controls was 0.66 mg/g wet weight in the former and 8.80 mg/g wet weight in the latter. Glycogen content in the cerebral cortex and myocardium was about 10 and 3 times more than in controls. 2. Polyglucosan extracted from the cerebral cortex, liver and myocardium had a longer exterior glucose chain than that in the liver of the control but a normal, alpha or beta 1,4-glucosidic linkage was observed. 3. The activities of glucose-6-phosphatase and amylo-1,6-glucosidase in the cerebral cortex, liver and myocardium were well preserved. The activities of acid maltase in the three organs mentioned above and of neutral maltase in the myocardium were elevated twice and one and half times more than the control. Phosphorylase levels in the myocardium were extremely small, while in the cerebral cortex and liver normal activities were observed. In light of these findings, glycogen metabolism in Lafora disease is discussed.
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PMID:Biochemical studies on tissues from a patient with Lafora disease. 17 19

Glycogen can be degraded in mammalian tissues by one of three isozymes of glycogen phosphorylase, termed muscle (M), liver (L) and brain (B) after the tissues in which they are preferentially expressed in adult animals, or by members of the family of alpha-glucosidases. In the current study, we have examined the developmental expression of these enzymes and their respective mRNAs in rabbit tissues, with particular emphasis on the developing lung, a tissue in which glycogen serves as an important source of carbon for surfactant phospholipid biosynthesis. Native gel activity assays and RNA blot hybridization analysis revealed that the B isoform of glycogen phosphorylase predominates in fetal and adult lung tissues, accompanied by a low level of expression of the M isoform. Total B and M phosphorylase activities increased during fetal lung development, with a peak at day 28 of gestation, then decreased to the adult level at term. This peak in activity coincided with the peak period of glycogen degradation in developing lung. While the increase in M isozyme activity was correlated with an increase in the level of its mRNA, B isoform mRNA showed no significant alteration during development, suggesting that the increase in B isoform activity is determined by a posttranscriptional mechanism. Analysis of phosphorylase mRNA levels in developing liver, skeletal muscle, brain and heart revealed a diverse expression pattern. The L isozyme mRNA was predominant at all time points in liver, the M isozyme was predominant at all time points in muscle, the B isozyme was predominant at all time points in brain, and heart contained a mixture of B and M mRNA in roughly equal ratios at all time points. Thus, our studies of phosphorylase mRNA in the rabbit provide no evidence for general predominance of the B isozyme in fetal tissues, or for isozyme 'switching' from the B to the L or M forms during development, as has been suggested by others. In addition to the increase in phosphorylase activity, acid, but not neutral alpha-glucosidase activity was found to increase significantly during fetal lung development, again with a peak at day 28 of gestation. Interestingly, RNA blot hybridization analysis with a probe for lysosomal alpha-glucosidase revealed no change in the level of expression of its 4 kb transcript in developing lung. Instead, we observed induction of a structurally related mRNA of 7.4 kb that peaked at day 28 of gestation. Hybridization with a sucrase/isomaltase-specific oligonucleotide excluded the possibility that the 7.4 kb transcript encodes this protein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental expression of glycogenolytic enzymes in rabbit tissues: possible relationship to fetal lung maturation. 195 55

To quantitatively examine the relationship between lysosomal acid alpha-glucosidase (LAAG, alpha-D-glucoside glucohydrolase, EC 3.2.1.20) inhibition and glycogen accumulation, rats were treated with castanospermine (CS), and liver lysosomal/mitochondrial fractions were analyzed for glycogen content and LAAG activity. Liver lysosomal glycogen accumulation positively correlated (r = 0.90) with the amount of LAAG inhibition when inhibition was about 50% or greater. Glycogen did not accumulate when LAAG inhibition was less than 50%. The route of CS administration had little effect on the amount of LAAG inhibition observed. In rats killed 17 hr after CS administration, the doses estimated to cause 50% LAAG inhibition were 0.77, 0.11, and 0.22 mg/kg for i.p., i.v., and oral administration respectively. After 89% inhibition of LAAG activity with a single oral dose of 10 mg CS/kg, LAAG activity returned to 50% of normal value in about 2.5 days. Accumulated glycogen disappeared as LAAG activity recovered. Surprisingly, twelve daily CS doses of 1 mg/kg had only a small cumulative effect on LAAG inhibition and did not cause more glycogen accumulation than a single dose.
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PMID:Quantitative relationship of lysosomal glycogen accumulation to lysosomal alpha-glucosidase inhibition in castanospermine-treated rats. 198 33

1. Glycogen, glucose, lactate and glycogen phosphorylase concentrations and the activities of glycogen phosphorylase a and acid 1,4-alpha-glucosidase were measured at various times up to 120 min after death in the liver and skeletal muscle of Wistar and gsd/gsd (phosphorylase b kinase deficient) rats and Wistar rats treated with the acid alpha-glucosidase inhibitor acarbose. 2. In all tissues glycogen was degraded rapidly and was accompanied by an increase in tissue glucose and lactate concentrations and a lowering of tissue pH. In the liver of Wistar and acarbose-treated Wistar rats and in the skeletal muscle of all rats glycogen loss proceeded initially very rapidly before slowing. In the gsd/gsd rat liver glycogenolysis proceeded at a linear rate throughout the incubation period. Over 120 min 60, 20 and 50% of the hepatic glycogen store was degraded in the livers of Wistar, gsd/gsd and acarbose-treated Wistar rats, respectively. All 3 types of rat degraded skeletal muscle glycogen at the same rate and to the same extent (82% degraded over 2 hr). 3. In Wistar rat liver and skeletal muscle glycogen phosphorylase was activated soon after death and the activity of phosphorylase a remained well above the zero-time level at all later time points, even when the rate of glycogenolysis had slowed significantly. Liver and skeletal muscle acid alpha-glucosidase activities were unchanged after death. 4. The decreased rate and extent of hepatic glycogenolysis in both the gsd/gsd and acarbose-treated rats suggests that this process is a combination of phosphorolysis and hydrolysis. 5. Glycogen was purified from Wistar liver and skeletal muscle at various times post mortem and its structure investigated. Fine structural analysis revealed progressive shortening of the outer chains of the glycogen from both tissues, indicative of random, lysosomal hydrolysis. Analysis of molecular weight distributions showed inhomogeneity in the glycogen loss; in both tissues high molecular weight glycogen was preferentially degraded. This material is concentrated in lysosomes of both skeletal muscle and liver. These results are consistent with a role for lysosomal hydrolysis in glycogen degradation.
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PMID:Post mortem glycogenolysis is a combination of phosphorolysis and hydrolysis. 227 18

Glycogen content and six major enzymatic activities involved in glycogen metabolism were analysed in chorionic villi (CV). Glycogen levels were found to be lower than those known to exist in liver and muscle. Activities of alpha-glucosidase, amylo-1,6-glucosidase, phosphorylase b and phosphorylase kinase were detectable by standard methods. The enzymatic activities of glucose-6-phosphatase and phosphorylase a were undetectable. These findings suggest that CV biopsies can be useful for first-trimester diagnosis of glycogen storage disease types II, III and VI, but not for type I (glucose-6-phosphatase deficiency).
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PMID:Enzymatic activity of glycogen metabolism in chorionic villi. 302 29

Glycogen deposition in vascular smooth muscle has been demonstrated previously in alpha-glucosidase deficiency but has not been clinically significant. Three sons of healthy, nonconsanguineous parents developed progressive proximal muscular weakness secondary to alpha-glucosidase deficiency. Each patient developed a fusiform basilar artery aneurysm, which was complicated by fatal rupture in two patients and a cerebellar infarction in the third. Postmortem examination demonstrated severe vacuolation of skeletal muscle, liver, and vascular smooth muscle with accumulation of periodic acid-Schiff-positive, diastase-sensitive material. In the surviving brother, similar glycogen deposition was demonstrated in the smooth muscle of the superficial temporal artery. Basilar artery aneurysm formation in this sibship may be a consequence of alpha-glucosidase deficiency.
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PMID:Alpha-glucosidase deficiency and basilar artery aneurysm: report of a sibship. 332 84

Castanospermine, an inhibitor of alpha-glucosidase activity, was injected into rats to determine its effects in vivo. Daily injections of alkaloid, at levels of 0.5 mg/g of body weight, or higher, for 3 days decreased hepatic alpha-glucosidase to 40% of control values, whereas alpha-glucosidase in brain was reduced to 25% of control values and that in spleen and kidney was reduced to about 40%. In liver, both the neutral (pH 6.5) and the acidic (pH 4.5) alpha-glucosidase activities were inhibited, but the former was more susceptible. On the other hand, beta-N-acetylhexosaminidase activity was elevated in the livers of treated animals, whereas beta-galactosidase activity was unchanged and alpha-mannosidase activity was somewhat inhibited. Livers of treated animals were examined by light and electron microscopy and compared to control animals to determine whether changes in morphology had occurred. In treated animals fed normal rat chow, the hepatocytes were smaller in size and simplified in structure, whereas the high-glucose diet lessened these alterations. Furthermore, in those animals receiving castanospermine at 1.0 mg or higher per g of body weight for 3 days, there was a marked decrease in the amount of glycogen in the cytoplasm, while a large number of lysosomes were observed that were full of dense, granular material. That this dense material was indeed glycogen was shown by the fact that it disappeared when blocks of fixed tissue were pretreated with alpha-amylase. Glycogen levels in liver, as measured either colorimetrically or enzymatically, were somewhat depressed at the higher levels of castanospermine.
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PMID:Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals. 388 59

Log-phase Tetrahymena were washed and resuspended in a dilute salt solution supplemented with glucose, acetate, pyruvate, or carmine, as desired, and then incubated for 5 h. Intra- and extracellular activities of acid phosphatase, alpha-glucosidase, and ribonuclease were assayed. Extracellular activities were corrected for proteolytic degradation. The three nutritive substrates affected both the amount and pattern of extracellular enzyme release, but carmine had no effect. Intracellular activities declined early in the starvation period, but partially recovered with time, particularly alpha-glucosidase activity. Acetate reduced the decline in acid phosphatase activity; acetate and glucose enhanced the recovery of alpha-glucosidase activity; carmine had no effect on intracellular enzyme activities. Protein content changed little and was unaffected by the addition of substrates. Glycogen content increased during incubation; acetate and glucose enhanced the increase.
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PMID:Lysosomal physiology in Tetrahymena. I. Effect of glucose, acetate, pyruvate, and carmine on intracellular content and extracellular release of three acid hydrolases. 463 42

Glycogen storage diseases of type I, II, III, IV, V and the other muscle types, were examined electron microscopically, biochemically and physicochemically. Glycogenosomes (glycogen containing vacuoles) were found in the affected tissues of type II, type III variant of muscle glycogen storage disease, type IV and muscle type phosphorylase b kinase deficiency (disorder of the phosphorylase b kinase activation mechanism). The acid alpha-glucosidase activity was decreased only in the case of type II glycogen storage disease (Pompe's disease). The other types of glycogen storage disease showed no decrease in acid alpha-glucosidase activity. Moreover, one patient with type II disease also revealed a decrease in neutral alpha-glucosidase activity. In all cases where glycogenosomes were found, the extracted glycogen macromolecules showed some molecular abnormality or deviation when compared with normal native glycogen macromolecules.
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PMID:Glycogen storage disease. Studies related to the mechanism of glycogenosome formation. 630 67


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