Glycogen metabolism Flashcards
Where is glycogen mainly found?
Liver and muscle
What prevents muscle glycogen from being used as a source of glucose for the body?
Lack of glucose-6-phosphatase
What are the major enzymes of glycogenesis?
Glycogen synthase
Branching enzyme
What are the two options needed to start the chain of glycogen?
UDP-glucose as a primer
Glycogenin
How does the branching enzyme work?
Removes 6-8 glucosyl residues from a chain of 10-11 and reattaches it by an alpha(1–>6) linkage
How does G6P become the G1P used in glycogenesis?
Phosphoglucomutase
How does G1P become UDP glucose used by glycogen synthase?
UDPG pyrophosphorylase using UTP and producing PPi
What are the major enzymes of glycogenolysis?
Glycogen phosphorylase
Debranching enzyme
What are the 2 enzymatic subunits of the debranching enzyme?
Oligo (1-4) to (1-4) glucan transferase
Amylo (1-6) glucosidase
What is the coenzyme required by glycogen phosphorylase?
PLP
How many residues remain before a branch after glycogen phosphorylase is finished?
4
What is the main product of glycogenolysis?
Glucose-1P
What is the function of the debranching enzyme?
Removes three glucosyl residues and reattaches them to main chain.
Cleaves (1-6) bond freeing last glucose-1P
What disease is characterized by accumulation of glycogen in lysosomes?
GSD type II - Pompe disease
What is the deficiency seen in Pompe disease?
acid maltase deficiency
How does phosphorylation affect glycogen synthase?
Inactivates it
How does phosphorylation affect glycogen phosphorylase?
Activates it
How does insulin regulate glycogenesis?
Promotes dephosphorylation of glycogen synthase by decreasing cAMP by activating phosphodiesterase
How do glucagon and epinephrine inhibit glycogenesis?
Promote phosphorylation of glycogen synthase by increasing cAMP by activating adenylate cyclase
What promotes glycogenolysis in muscles?
Epinephrine only
How does calcium influence glycogen metabolism?
Released by nerve impulses during muscle contraction. It will bind with calmodulin that activates muscle phosphorylase kinase, thereby activating glycogen phosphorylase
Increases glycogenolysis in muscles
What are the inheritances patterns for GSDs I - VI?
Autosomal recessive
What enzyme is deficient in Von Gierke’s disease (GSD Ia)?
Glucose-6-phosphatase
What enzyme is deficienct in Cori disease (GSD III)?
Debranching enzyme
What enzyme is deficient in Anderson disease (GSD IV)?
Branching enzyme
What enzyme is deficient in McArdle disease (GSD V)?
Muscle phosphorylase
What enzyme is deficient in Hers’ disease (GSD VI)?
Hepatic glycogen phosphorylase
What enzyme is deficient in GSD Ib?
Glucose-6P translocase
What are the signs of Von Gierke’s disease?
Hepato- and reno-megaly
Fasting hypoglycemia
Severe lactic acidemia - affects Cori cycle
Ketosis
Hyperlipidemia
Fatty liver
Hyperuricemia
What are physical features in children with Von Gierke’s disease?
Doll-like face
Protruding abdomen
What is the most severe GSD?
Pompe disease - type II
What are signs of Pompe disease in children?
Muscle hypotonia
Muscle weakness
Death from cardiac failure by age 2
What are signs of Pompe disease in adults?
Muscle dystrophy
What are signs of Cori disease?
Fasting hypoglycemia
Hepatomegaly in infants
Accumulation of abnormal glycogen with shorter then normal branches
What are other names for Cori disease (GSD III)?
Forbe disease
Limit dextrinosis
What are signs of Anderson disease?
Accumulation of abnormal glycogen with few branch points and longer branches
Hepatosplenomegaly
Death from heart or liver failure by 2
What are signs of McArdle syndrome?
Poor exercise tolerance - muscle cramping and early fatigue
Normal liver enzymes
No rise in blood lactate after exercises
Glycogen with normal structure accumulation in muscles
Myoglobinemia
Myoglobinuria
