Glycogen Metabolism and Glycogen Storage Diseases Flashcards Preview

DM Biochem > Glycogen Metabolism and Glycogen Storage Diseases > Flashcards

Flashcards in Glycogen Metabolism and Glycogen Storage Diseases Deck (12)
Loading flashcards...
1

explain how glycogen degradation can be allosterically activated by calcium

  • glycogen phosphorylase kinase contains the subunits αβγδ 
    • α and β can be phosphorylated
    • γ has catalytic activity
    • δ acts as calmodulins
  • binding of Ca to the δ subunit results in a conformational shift that activates the enzyme without being phosphorylated
  • allosteric Ca activation takes place in muscle during muscle contraction and in the liver following binding of hormones that use the Ca ion messenger system

2

muscle contraction generates ____ and ____ which are allosteric activators of muscle glycogen degradation

muscle contraction generates Ca ions and AMP which are allosteric activators of muscle glycogen degradation

  • Ca ions activate the dephosphorylated glycogen phosphorylase kinase
    • GPK phosphorylates and activates glycogen phosphorylase
      • glycogen phosphorylase is phosphorylated
  • AMP activates the dephosphorylated glycogen phosphorylase

3

summarize regulation of glycogen synthase

4

summarize glycogen phosphorylase kinase regulation

5

summarize glycogen phosphorylase regulation

6

describe Von Gierke Disease 

  • Type I 
  • high glycogen content in liver and kidney with normal structure
    • hepato-nephro megaly
  • glucose 6-phosphatase is deficient in liver and kidney
  • treatment = uncooked corn starch or nocturnal gastric glucose infusions 
  • clinical features:
    • hepato-nephro-megaly
    • very severe fasting hypoglycemia
    • lactic acidemia
    • hyperuricemia
    • hyperlipidemia
  • 2 types:
    • 1a = deficiency of G6Pase in the ER
    • 1b = deficiency of G6P translocase (ER)

7

describe Pompe Disease

  • type II
  • deficiency of lysosomal a1,4 glucosidase (aka acid maltase)
    • some cytosolic glycogen is always captured in autophagosomes and delivered to lysosomes; acid maltase cleaves this glycogen to release free glucose into the cytosol
  • lysosomal glycogen accumulation in heart, muscle and liver
    • massive cardiomegaly

8

describe Cori Disease

  • Type III 
  • deficiency of the debranching enzyme (4:4 transferase)
  • abnormal glycogen structure with short outer branches (limit dextrinoses)
  • muscular weakness, mild hypoglycemia, cardiomyopathy
  • considered a muscular dystrophy

9

describe Andersen Disease

  • type IV
  • abnormal glycogen synthesis and structure
  • deficiency of the glycogen branching enzyme (4:6 transferase)
    • characterized by abnormal glycogen structure with long glucose chains and less branches

10

describe McArdle Syndrome

  • type V
  • abnormal gylcogen degradation in muscle; deficiency of muscle phosphorylase
  • high levels of glycogen with normal structure in muscle
  • patients show rhabdomyolysis after forced exercise due to lack of ATP, serum CK-MM is increased
  • muscle weakness test for diagnosis:
    • normal = lactate increases during exercise
    • McArdle = no lactate increase because the muscle glycogen degradation is reduced and less lactate is formed

11

describe Hers Disease

  • type VI
  • abnormal glycogen degradation in the liver
  • high levels of hepatic glycogen (normal structure)
  • deficiency of hepatophosphorylase (muscle isozyme is normal)
  • clinical features:
    • hepatomegaly
    • mild fasting hypoglycemia

12

describe Tarui Disease

  • type VII
  • reduced activity of the of PFK-1 in the muscle (MM) and RBCs (ML)
    • liver isozyme (LL)= normal
  • clinically similar to McArdle leading to muscle cramping due to lack of ATP
  • hemolysis occurs due to PFK-1 deficiency in RBCs