1 / 16

Glycogen Storage Diseases:

Glycogen Storage Diseases:. Overview of Glycogen Metabolism. Excess glucose stored as glycogen Glucose units joined by α -1,4 and α -1,6 glycosidic bonds Glucosyl chains are branched Fasted state (catabolic)—glycogen breakdown Fed state (anabolic)—glycogen synthesis.

ura
Download Presentation

Glycogen Storage Diseases:

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Glycogen Storage Diseases:

  2. Overview of Glycogen Metabolism • Excess glucose stored as glycogen • Glucose units joined by α-1,4 and α -1,6 glycosidic bonds • Glucosyl chains are branched • Fasted state (catabolic)—glycogen breakdown • Fed state (anabolic)—glycogen synthesis

  3. Anabolism – Glycogenesis • Glycogen synthaseextends chains (α-1,4) from non-reducing ends; uses UDP-glucose as substrate • Branching enzyme (transferase function) required to form branched chains; forms α-1,6 glycosidic bonds; moves 7 residues

  4. Anabolism – Glycogenesis • Glycogen synthase needs to be activated for glycogenesis to occur • Enzymes involved in breakdown need to be deactivated • Fed state dominated by insulin • Protein phosphatase I activated (also inactivates phosphorylase kinase, not shown below)

  5. Catabolism - Glycogenolysis • Glycogen phosphorylase removes glucosyl unit from non-reducing end by phosphorylysis (releases glucose-1-phosphate) • Debranching enzyme (transferase activity) moves 3 glucose units to another branch; hydrolyzes α-1,6 linkage with glucosidase function (same polypeptide chain for eukaryotes)

  6. Catabolism - Glycogenolysis

  7. GSD Type 0 • An inherited genetic disease • Enzyme affected: glycogen synthase • The body is unable to store glycogen • LIVER: Chromosome 12 -hypoglycemia when fasting -hyperglycemia right after meals • MUSCLE: Chromosome 19 -frequent fatigue and muscle cramps

  8. GSD Type 1 • Edgar von Gierke’s Disease • Most common disease type (approximately 1 in 20,000 infants) • Characterized by: • -an abnormally large abdomen due to an accumulation of glycogen in the liver • -prominent hypoglycemia in between meals (may cause convulsions in infants)

  9. Deficiency of the Enzyme glucose-6-phosphatase Glucagon Cascade • An inherited defect in chromosome 17 • The body is not able to break down glycogen into glucose

  10. Prolonged hypoglycemia can cause

  11. GSD Type IIPompe’s disease, acid maltase deficiency • Alpha-1,4-glucosidase (lysosomalglucosidase; acid maltase) • Catalyzes α-1,4- and α-1,6-glucosidic linkages (hydrolysis) • Lysosomes dispose/recycle waste products • acid alpha-glucosidase gene, mapped in chromosome 17 • Autosomal recessive disorder • Diagnosis: Determining activity of acid alpha-glucosidaseenzyme • Muscle weakness and heart problems are the most common features even though defected enzyme is present in all tissues

  12. GSD Type III / Cori Disease • Caused by mutation in gene responsible for making the glycogen debranching enzyme • It is inherited and leads to abnormal glycogen in the body • Divided into types IIIa, IIIb, IIIc, IIId • Affects 1 in 100,000 individuals, whereas it affects 1 in 5,400 individuals of North African Jewish

  13. GSD Type IV / Anderson Disease • Caused by mutation in gene responsible for making the glycogen branching enzyme • It is inherited and leads to abnormal glycogen in the body • Divided into 5 subtypes, which vary in severity, signs and symptoms • Affects 1 in 600,000 to 800,000 individuals world wide

  14. GSD Type V / McArdle disease • Caused by mutation in gene which is responsible for myophosphorylase • It is inherited and leads to inability to break down glycogen in muscle cells • Symptoms include exercise intolerance marked by rapid fatigue and cramps in exercising muscles • Generally rare but affects 1 in 100,000 individuals

  15. GSD Type VIHers disease, liver phosphorylase deficiency • Liver glycogen phosphorylase • Early signs and symptoms frequently includes hepatomegaly and hypoglycemia; growth retardation, ketosis, and hyperlipidemia.

  16. GSD Type VIITarui disease, muscle phosphofructokinase deficiency • Phosphofructokinase (muscle) • PFKM, chromosome 12 • Exercise intolerance (due to muscle pain, cramping, fatigue, and tenderness), myopathy, and hemolysis; myoglobinuria may develop (dark-red or red-brown urine)

More Related