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80 terms

Glycogen

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What is the optimum glucose concentration of the blood?
5 mmol/L
What are the 2 major sources of blood glucose?
diet

breakdown of hepatic glycogen stores
Glycogenesis
glycogen biosynthesis
Glycogenlysis
glycogen breakdown
Is glycogenesis endergonic or exergonic?
endergonic
What is the primer for glycogenesis?
glycogenin
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?
glycogen synthase

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 rate-limiting step in glycogenolysis?
glycogen phosphorylase
What is the function of glycogen phosphorylase?
removes a single glucose-1-phosphate from the glycogen core
What enzyme rearranges glucose-1-phosphate to glucose-6-phosphate?
phosphoglucomutase
How does glucose leave the liver?
GLUT2
In what organelle is hepatic glucose-6-phosphatase located?
ER lumen
Name 2 allosteric activators of muscle glycogen phosphorylase
AMP

Ca2+
Name an allosteric inhibitor of muscle glycogen phosphorylase
glucose-6-phosphate
Describe the pathway of muscle activation and glycogenolysis
Beta-receptor (epinephrine)

cAMP

protein kinase A

phosphorylase kinase (phosphorylated)

glycogenolysis (glycogen phosphorylase a)

glycolysis

fructose-1,6-phosphate

TCA

oxidative phosphorylation
Does glucagon affect muscle cells?
glucagon has no effect on muscle
Where is glucagon produced?
pancreatic alpha-cells
Where is insulin produced?
pancreatic beta-cells
Where is epinephrine produced?
adrenal medulla
Name an activator of hepatic glycogen synthase
glucose-6-phosphate
Name 3 inhibitors of hepatic glycogen phosphorylase
glucose-6-phosphate

ATP

glucose
When is liver phosphorylase A active?
phosphorylated
When is liver phosphorylase inactive?
dephosphorylated
What type of receptor is the glucagon receptor?
G protein coupled receptor
Glycogen storage disease
inherited enzyme deficiencies that lead to the storage of glycogen in abnormal amounts and sometimes with an abnormal structure
Which GSD is caused by glucose-6-phosphatase deficiency?
Von Gierke's disease (type I)
Which GSD is caused by lysosomal alpha-1,4-glucosidase deficiency?
type 2: Pompe's disease
Name 2 characteristics of hepatic glycogen storage diseases
hypoglycemia

hepatomegaly
Name 2 characteristics of myopathic (muscle) glycogen storage diseases
muscle weakness and cramps
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
Does McArdle's disease affect liver enzymes?
no
What is myoglobinuria? Which GSD is associated with myoglobinemia?
myoblogin in urine

McArdle's disease
What blood marker would suggest McArdle's disease?
increased CKMM
What is the prognosis for McArdle's disease?
avoid strenuous exercise
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
Symptoms of what GSD are similar to Tarui's disease
Type V: McArdle's disease
Name the 4 GSD's affecting the Liver
type I: von Gierke

type III Cori

type IV: Andersen

type VI: Hers
type Ib glycogen storage disease
deficiency in glucose-6-phosphate transporter
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?
hypoglycemia

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
Why is hypoglycemia mild in Hers disease?
liver can still make glucose from pyruvate
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 transfers -OH group to glycogenin?
tyrosine residue
To which end are glucose unit added?
non-reducing ends
What is UDP-glucose?
group transfer reagent carrying an activated form of glucose
Glucokinase requires which co-factor?
Mg2+
What enzyme catalyzes the reaction from glucose-6-phosphate to glucose-1-phosphate?
phosphoglucomutase
What enzyme removes branches from the glycogen core?
debranching enzyme
In what situation does glycogenolysis occur in muscle tissue?
prolonged exercise
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
Are muscle and liver tissues affected by insulin?
yes, both
Hypoglycemia will lead to secretion of what hormone(s)?
glucagon

adrenaline
Hyperglycemia will lead to secretion of what hormone(s)?
insulin
How does glucagon affect glycogenolysis?
rapid activation
How does insulin affect glycogenolysis?
inhibitory
How does adrenaline affect glycogenolysis?
rapid activation
In glycogen synthesis is hepatic glycogen synthase phosphorylated or de-?
dephosphorylated
In glycogenolysis, is hepatic glycogen phosphorylase phosphorylated or de-?
phosphorylated
Name an activator of muscle glycogen synthase
glucose-6-phosphate
Name 2 activators of muscle glycogen phosphorylase
Ca2+

AMP
Name 2 inhibitors of glycogen phosphorylase
glucose-6-phosphate & ATP
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)
For McArdle's disease, would blood lactate rise during strenuous exercise?
no
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
Why does hyperurecemia lead to gout in type I GSD?
increased activity of the PPP --> increased purine synthesis