scholarly journals Identification of Novel Genes and Variations Associated to Glycolytic Potential Based on Pig Model

2018 ◽  
Author(s):  
Wangjun Wu ◽  
Zengkai Zhang ◽  
Zhe Chao ◽  
Bojiang Li ◽  
Caibo Ning ◽  
...  
Keyword(s):  
Paired Comparison ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Catalytic Subunit ◽  
Pig Model ◽  
Glycogen Storage Diseases ◽  
Glycolytic Potential ◽  
Sequencing Library ◽  
Comparison Groups ◽  
Large Indels

ABSTRACTIn livestock, glycolytic potential (GP) is a critical indicator for evaluating the meat quality. To date, two major genes protein kinase AMP-activated γ3 non-catalytic subunit gene (PRKAG3) and phosphorylase kinase catalytic subunit gamma 1(PHKG1), and corresponding cause mutations influencing GP have been confirmed in pigs. Therefore, the aim of this study to identify the novel candidate genes and variations related to GP-related traits using a four-hybrid pig model [Pietrain (P)× Duroc (D)] ×[(Landrace) ×(Yorkshire)]. We totally constructed six RNA-seq libraries using longissimus dorsi (LD) muscles, and each library contained two higher GP (H) or two lower GP (L) individuals. A total of 525, 698 and 135 differentially expressed genes (DEGs) were identified between H11 vs L11, H9 vs L9, and H5 vs L5 groups using PossionDis method, respectively. Notably, we found 97 non-redundant DEGs were mapped to GP related QTLs from three paired comparison groups. Moreover, 69 DEGs were identified between H (H11, H9 and H5) and L (L11, L9 and L5) groups using NOIseq method. Additionally, 1,076 potential specific SNPs were figured out between H and L groups, and approximately 40 large Indels with a length ≥ 5bp were identified in each sequencing library. In conclusion, our data provide foundation for further confirming the key genes and the functional mutations affecting GP-related traits in pigs, and also pave the way for elucidating the underling molecular regulatory mechanisms of glycogen metabolism in future study. Moreover, this study might provide valuable information for study on human glycogen storage diseases.

Enzymes of Glycogen Metabolism in Human Skin with Particular Reference to Differential Diagnosis of the Glycogen Storage Diseases

1971 ◽  
Vol 40 (3) ◽  
pp. 261-269 ◽  
Author(s):  
P. D. Leathwood ◽  
Brenda E. Ryman
Keyword(s):  
Glycogen Storage Disease ◽  
Glycogen Phosphorylase ◽  
Storage Disease ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Debranching Enzyme ◽  
Epidermal Tissue ◽  
Glycogen Storage Diseases ◽  
Muscle Phosphorylase ◽  
Type V

1. A vacuum skin-blistering technique has been successfully applied and the human epidermal tissue so obtained has been examined for glycogen content and some of the enzymes involved in glycogen metabolism. 2. Normal values for glycogen phosphorylase, acid α-glucosidase and amylo-1,6-glucosidase (debranching enzyme) in epidermis are reported. Glucose 6-phosphatase activity was not detected. 3. Examination of two patients with Type II glycogen storage disease (Pompe's Disease—lack of lysosomal acid α-glucosidase) revealed an absence of the acid α-glucosidase in their skin. 4. The enzymic lesion in Type V glycogen storage disease (McArdle's Disease—lack of muscle phosphorylase) was not reflected in the epidermal tissue of a patient and a normal level of the enzyme was observed.

scholarly journals Biochemical and clinical aspects of glycogen storage diseases

2018 ◽  
Vol 238 (3) ◽  
pp. R131-R141 ◽  
Author(s):  
Sara S Ellingwood ◽  
Alan Cheng
Keyword(s):  
Genetic Disorders ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Clinical Aspects ◽  
Branch Points ◽  
Storage Diseases ◽  
Progressive Myoclonus Epilepsy ◽  
Glycogen Storage Diseases ◽  
Myoclonus Epilepsy ◽  
Chain Lengths

The synthesis of glycogen represents a key pathway for the disposal of excess glucose while its degradation is crucial for providing energy during exercise and times of need. The importance of glycogen metabolism is also highlighted by human genetic disorders that are caused by mutations in the enzymes involved. In this review, we provide a basic summary on glycogen metabolism and some of the clinical aspects of the classical glycogen storage diseases. Disruptions in glycogen metabolism usually result in some level of dysfunction in the liver, muscle, heart, kidney and/or brain. Furthermore, the spectrum of symptoms observed is very broad, depending on the affected enzyme. Finally, we briefly discuss an aspect of glycogen metabolism related to the maintenance of its structure that seems to be gaining more recent attention. For example, in Lafora progressive myoclonus epilepsy, patients exhibit an accumulation of inclusion bodies in several tissues, containing glycogen with increased phosphorylation, longer chain lengths and irregular branch points. This abnormal structure is thought to make glycogen insoluble and resistant to degradation. Consequently, its accumulation becomes toxic to neurons, leading to cell death. Although the genes responsible have been identified, studies in the past two decades are only beginning to shed light into their molecular functions.

Glycogen storage diseases

2010 ◽  
pp. 1596-1603 ◽  
Author(s):  
Philip Lee ◽  
Kaustuv Bhattacharya
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Failure To Thrive ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Metabolic Disturbances ◽  
Dietary Regimen ◽  
Exogenous Glucose ◽  
Glycogen Storage Diseases ◽  
Constant Source

Glycogen metabolism is regulated by a number of different enzymes, defects in any of which result in several types of glycogen storage disease. Types I, III, VI, and IX have predominantly hepatic manifestations: they typically present in infancy with failure to thrive and hepatomegaly, and they are associated with fasting hypoglycaemia. Diagnosis can be made in many cases by detection of gene mutation or functional tests of red blood cells or white blood cells. Most patients require an intensive dietary regimen providing a constant source of exogenous glucose, particularly in childhood. In illness, glucose requirements increase and it is necessary to continue to provide glucose either enterally or intravenously to prevent hypoglycaemia and secondary metabolic disturbances....

scholarly journals Glycogen Storage Disease 1b: Diagnosis and Workup of a Novel Mutation

2016 ◽  
Vol 36 (1) ◽  
pp. 85-87
Author(s):  
Rama Krishna Sanjeev ◽  
Swathi Shetty ◽  
Arun Harith ◽  
Bindu T Nair ◽  
Sajith Surendran
Keyword(s):  
Storage Disease ◽  
Antenatal Diagnosis ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Carrier State ◽  
Glycogen Storage Diseases ◽  
Added Benefit ◽  
Work Up

Glycogen Storage diseases (Glycogenoses) are a diverse group of disorders, numbering more than 12, resulting from deficiencies of various enzymes & transport proteins in the pathways of glycogen metabolism. GSD 1 is caused by absence or deficiency of glucose-6-phosphatase activity in the liver, kidney or intestinal mucosa. In GSD 1(b), the enzyme which transports Glucose-6-Phosphate across the microsomal membrane is defective, thereby resulting in accumulation of Glycogen. The clinical features of 1a & 1b are similar with fasting hypoglycaemia, hepatomegaly, growth retardation and metabolic abnormalities except for the presence of neutropenia with recurrent gingivitis in GSD 1b. A genetic diagnosis solves this conundrum with the added benefit of antenatal diagnosis of future pregnancies & identification of carrier state in patients. We report the work up of an infant with suspected GSD where a novel mutation with heterozygous carrier state in the parents was diagnosed by genetic testing.J Nepal Paediatr Soc 2016;36(1):85-87.

scholarly journals Mechanism of glycogen synthase inactivation and interaction with glycogenin

2021 ◽  
Author(s):  
Laura Marr ◽  
Dipsikha Biswas ◽  
Leonard A Daly ◽  
Christopher Browning ◽  
John Pollard ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Moderate Increase ◽  
Storage Diseases ◽  
Future Studies ◽  
Glycogen Storage Diseases ◽  
Structure Lead

The macromolecule glycogen is the major glucose reserve in eukaryotes and defects of glycogen metabolism and structure lead to glycogen storage diseases and neurodegeneration. Glycogenesis begins with self-glucosylation of glycogenin (GN), which recruits glycogen synthase (GS). GS is activated by glucose-6-phosphate (G6P) and inactivated by phosphorylation, but how these opposing processes are coupled is unclear. We provide the first structure of phosphorylated human GS-GN complex revealing an autoinhibited GS tetramer flanked by two GN dimers. Phosphorylated N- and C-terminal tails from two GS protomers converge to form dynamic "spike" regions, which are buttressed against GS regulatory helices. This keeps GS in a constrained "tense" conformation that is inactive and more resistant to G6P activation. Mutagenesis that weaken the interaction between the regulatory helix and phosphorylated tails leads to a moderate increase in basal/unstimulated GS activity, supporting the idea that phosphorylation contributes to GS inactivation by constraining GS inter-subunit movement. We propose that multivalent phosphorylation supports GS autoinhibition through interactions from a dynamic "spike" region, thus allowing a "tuneable rheostat" for regulating GS activity. Our structures of human GS-GN provide new insights into the regulation of glycogen synthesis, facilitating future studies of glycogen storage diseases.

scholarly journals Neurological Characteristics of Pediatric Glycogen Storage Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Julio Henrique Muzetti ◽  
Daniel Almeida do Valle ◽  
Mara L. S. Ferreira Santos ◽  
Bruno Augusto Telles ◽  
Mara L. Cordeiro
Keyword(s):  
Metabolic Control ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Metabolism ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Type I ◽  
Cross Sectional ◽  
Glycogen Storage Diseases ◽  
Multigene Panel

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.

Glycogen storage diseases

2020 ◽  
pp. 1985-1993
Author(s):  
Robin H. Lachmann ◽  
Timothy M. Cox
Keyword(s):  
Tissue Injury ◽  
Genetic Disorders ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Exercise Intolerance ◽  
Dietary Interventions ◽  
Glycogen Storage Diseases ◽  
Marked Accumulation ◽  
Exercise Programmes

Glycogen is a highly branched glucose polymer with a compacted structure found predominantly in liver and muscle. Liver glycogen is important in the maintenance of euglycaemia during fasting; muscle glycogen is an immediate source of glucose for energy production during exercise. Genetic disorders affecting proteins that regulate glycogen metabolism and transport, as well as those which catalyse its biosynthesis and breakdown, cause marked accumulation of glycogen in diverse tissues, and pathological glycogen often has an abnormal macromolecular structure. Depending on the enzyme system involved, diseases of glycogen metabolism principally affect liver and muscle. Clinical features are related to pathological glycogen in tissues and/or failure to release glucose. Glycogen storage is associated with organomegaly and tissue injury. Fasting hypoglycaemia occurs where hepatic breakdown of glycogen is impaired. Glycogen diseases that affect muscle usually present with rhabdomyolysis, exercise intolerance, and muscle pain or weakness. Formerly, diseases of glycogen metabolism were diagnosed by showing excess storage of glycogen in the tissue of interest, accompanied by reduced activity of particular glycogen-metabolizing enzymes. Currently, where available, molecular analysis of genomic DNA is the preferred method for providing a definitive diagnosis. The mainstay of treatment of glycogen diseases affecting the liver is dietary, including pre-emptive management of hypoglycaemia that is readily provoked by fasting. Dietary interventions may also ameliorate some of the glycogen diseases that affect muscle, and weakness and pain after exertion can be improved by graduated exercise programmes in some patients.

Glycogen Storage Diseases

2018 ◽  
Author(s):  
Tammy Wang ◽  
Jocelyn Wong ◽  
Anita Honkanen
Keyword(s):  
Skeletal Muscles ◽  
Autosomal Recessive ◽  
Clinical Presentation ◽  
Glycogen Metabolism ◽  
Glycogen Storage ◽  
Muscle Relaxants ◽  
Storage Diseases ◽  
Glycogen Storage Diseases ◽  
Organ Systems ◽  
Glucose Storage

Glycogen storage diseases result from deficiencies of various enzymes or proteins in the pathways of glycogen metabolism. The reduction in effective glucose storage and/or mobilization results in hypoglycemia and accumulation of glycogen in tissues. Diagnosis can occur at any age, from infancy to adulthood, depending on the pathway affected and the degree of enzyme deficiency. The clinical presentation varies, but the most commonly affected organ systems include the heart, liver, and skeletal muscles. In addition to the morbidity that can occur from dysfunction of these organs, important anesthetic implications include administration of glucose-containing fluids to avoid hypoglycemia, monitoring for acidosis, and caution with use of depolarizing muscle relaxants because of the potential risk of hyperkalemia and rhabdomyolysis. Inheritance is commonly autosomal recessive.

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