What is the purpose of UDP-glucose?
the synthesis of sugar nucleotides is irreversible; it cannot be diverted to other pathways such as glycolysis
nucleotide moiety possesses groups that can undergo enzymatic noncovalent interactions and thus contributing to catalytic activity
What is the key regulatory enzyme of glycogenesis? Why?
UDP glucose is involved in glycolipid and glycoprotein synthesis
What type of bonds are formed by glycogen synthase?
alpha 1-4 glycosidic linkages in the main chain
What is the purpose of branch points (2)?
increase solubility of glycogen molecule
create numerous non-reducing ends for rapid synthesis and degradation
What is the function of glycogen phosphorylase?
removes a single glucose-1-phosphate from the glycogen core
Describe the pathway of muscle activation and glycogenolysis
protein kinase A
phosphorylase kinase (phosphorylated)
glycogenolysis (glycogen phosphorylase a)
Glycogen storage disease
inherited enzyme deficiencies that lead to the storage of glycogen in abnormal amounts and sometimes with an abnormal structure
Which GSD has the following characteristics? glycogen of normal structure accumulates in lysosomes
blood glucose is normal
liver, muscle & heart affected cardiomegaly can occur
Pompe's (type II)
McArdle's disease (type V)
muscle glycogen phosphorylase deficiency (or absence)
abnormally high glycogen stores in muscle w/normal structure
diminished exercise tolerance-blood lactate levels don't rise during exercise
liver enzymes are normal
What is myoglobinuria? Which GSD is associated with myoglobinemia?
myoblogin in urine
Tarui's disease (type VII)
deficiency of PFK-1, affects skeletal muscle & RBC's
symptoms similar to type V (McArdle's) ---> but also causes erythrocyte HEMOLYSIS
ability to obtain energy from glucose & glycogen impaired
Name the 4 GSD's affecting the Liver
type I: von Gierke
type III Cori
type IV: Andersen
type VI: Hers
Why does hypoglycemia leads to excessive TAG degradation in adipose tissue?
insulin levels drop, leading to activation of hormone-sensitive lipase, free fatty acids for energy
What changes occur in blood chemistry for type I GSD?
hyperlipidemia & ketosis
hyperurecemia leading to gout
Cori's (Type III) GSD
defect or absence of DEbranching enzyme
accumulation of abnormal glycogen - w/short outer branches
Anderson's (type IV) GSD
defect or absence of Branching enzyme
abnormal glycogen - few branch points, so less soluble than normal
liver treats abnormal glycogen as 'foreign' - produces large amounts of fibrous tissue - hepatomegaly
Hers (type VI) GSD
absence or deficiency of Hepatic (liver) glycogen phosphorylase deficiency - muscle enzyme normal
Symptoms of Hers disease
high levels of hepatic glycogen - hepatomegaly
Symptoms are similar to Type I (Von Gierke's) only milder
What is the function of glycogen phosphorylase?
release glucose-1-phosphate by breaking alpha-1,4-bonds
Describe the structure of glycogen
alpha(1,4) glycosidic bonds
alpha(1,6) glycosidic branches every 8-12 residues
What enzyme catalyzes the reaction from glucose-6-phosphate to glucose-1-phosphate?
Describe the dual stimulation of muscle activation and glycogenolysis
Ca2+-calmodulin complex and AMP on phosphorylase kinase
AMP stimulates PFK-1 and and thus glycolysis
AMP stimulates phosphorylase kinase
Explain what happens when glucagon binds to its receptor (up until phosphorylation events)
glucagon binds to its receptor, causing GDP to become GTP; this activates the g-protein
adenylyl cyclase creates cAMP from ATP
cAMP activates protein kinase A
Describe the effects of protein kinase A on Inhibitor - I
protein kinase A phosphorylates inhibitor-I, which becomes active
inhibitor - I inhibits phosphoprotein phosphatase, which is responsible for converting glycogen phosphorylase to its inactive form
Describe the effects of protein kinase A on phosphorylase kinase
protein kinase A phosphorylates phosphorylase kinase-b, which activates the enzyme
phosphorylase kinase-a phosphorylates glycogen phosphorylase-b, which becomes active
glycogen phosphorylase-a can then activate glycogenolysis
Describe the effects of protein kinase A on glycogen synthase
protein kinase A phosphorylates glycogen synthase-a, which becomes inactive
In muscle, how can phosphorylase kinase be activated without phosphorylation?
Ca2+ binds to the calmodulin subunit of phosphorylase kinase, activating it without phosphorylation
What is the main mechanism behind anti-glucagon effects?
dephosphorylation of glycogen synthase (activates the enzyme)
What is the rate-limiting step of glycogen biosynthesis?
formation of the alpha-1,4-bond with the primer at the non-reducing end
UDP-glucose + (glycogen)n <---> (glycogen)n+1 + UDP
Mneumonic for the 7 GSD
"Viagra Pills Cause A Mostly Happy Time": Von Gierke's, Pompe's,
Cori's, Anderson's, McArdle's, Her's, Tarui's