Glycogen Metabolism (Exam 1) Flashcards
Glycogen metabolism has 2 pathways. What are they?
1) glycogenolysis (break down glycogen)
2) glycogenesis (make glycogen)
Where is glycogen found?
liver (used to maintain blood sugar) and muscle tissue (used for muscle energy)
Can glycogen reach organelles within a cell?
no, its too big and will stay in the cytoplasm
Excess glucose can be stored as a highly branched polymer called _____________ in animals
glycogen
What molecules makes up glycogen?
alpha D glucose molecules
What o-glycosidic bonds are in glycogen?
alpha 1,4 and alpha 1,6
alpha 1,6 is the branching bond and glycogen has the highest degree of branching
Is glycogen a reducing sugar or non-reducing sugar?
non-reducing sugar bc the reducing end is bound to a protein called glycogenin
What is the glucose storage form in plants?
amylose OR amylopectin (they’re both starches)
amylose is alpha D glucose molecules and has only alpha 1,4 bonds (its linear, no branching)
amylopectin is also alpha D glucose but it has both alpha 1,4 and alpha 1,6 bonds
What does alpha mean in o-glycosidic bonds with glycogen?
C1 is pointed downward
Compared to fats, the body only stores a small amount of glycogen. Why?
fats are hydrophobic, glycogen is hydrophilic
there is an unlimited amount of room for fat because its hydrophobic
Glycogen is a highly branched _______________________ composed of alpha D glucose bound by alpha 1,4 (linear structure) and alpha 1,6 (branch point) o glycosidic bonds
homopolysaccharide
What is stage 1 of glycogen synthesis (glycogenesis)?
formation of UDP glucose
What does stage 1, formation of UDP glucose, in glycogenesis require?
2 ATP
Which has a higher affinity- hexokinase (HK) or glucokinase (GK)?
HK has a higher affinity
Which has a smaller Km and Vmax- HK or GK?
HK has a smaller Km and Vmax
Which has a bigger Km and Vmax- HK or GK?
GK has a bigger Km and Vmax
Which tissues have HK? Which tissues have GK?
every tissue has HK, but GK is only in the liver
so, liver has both HK and GK
muscles have only HK
During stage 1 of glycogenesis, glucose enters tissue cells and uses 1 ATP with HK or GK to make….
glucose 6 phosphate
During stage 1 of glycogenesis, glucose enters tissue cells and uses 1 ATP with HK or GK to make glucose 6 phosphate (G6P). G6P will be converted to a G1P, which is an isomerization reaction. What enzyme converts G6P to G1P?
phosphoglucomutase
note: its very easy to go back and forth between G6P and G1P, so this is not the rate limiting step because the rate limiting step should be the hardest one
If you eat a high carb meal then what enzyme will convert glucose to G6P in glycogenesis?
glucokinase (GK) because it has high Vmax
During stage 1 of glycogenesis, glucose enters tissue cells and uses 1 ATP with HK or GK to make glucose 6 phosphate (G6P). G6P will be converted to a G1P, which is an isomerization reaction with phosphoglucomutase. G1P then undergoes another reaction with UTP (considered the 2nd ATP in stage 1) and will make….
UDP glucose
What is the precursor for tyrosine?
phenylalanine will undergo reaction with phenylalanine hydroxylase to make tyrosine
During stage 2 of glycogenesis, UDP glucose binds to….
tyrosine-glycogenin
**will bind at the reducing end
Glycogenin is an enzyme and the anchor protein for UDP glucose and is located in the…..
cytoplasm
During stage 2 of glycogenesis, the glycogen chain is initiated by binding a UDP-glucose molecule to a tyrosine residue on glycogenin which has its own __________________________ activity
glycoyl transferase (also known as amylo-transglycosylase activity)
Which stage of glycogenesis is the rate limiting stage?
stage 3
What is the rate limiting enzyme in glycogenesis?
glycogen synthase
What is the substrate in stage 3 of glycogenesis?
UDP-glucose
During stage 3 of glycogenesis, glycogen synthase adds UDP glucose to the ______________ end of a chain. Glycogen synthase creates ____________ o-glycosidic bonds. Each chain in glycogen has about 10 glucose molecules lined together
non-reducing, alpha 1,4
Which enzyme is used in stage 4 of glycogenesis?
branching enzyme
During stage 4 of glycogenesis, the branching enzyme places a branch point at about every 10 residues, transferring the terminal 7 from the ______________ end and joining them with an alpha 1,6 o-glycosidic bond to form the branch. Glycogen synthase continues to extend from the non-reducing ends of both branches. The process is repeated to create the highly branched glycogen
non-reducing
Where does glycogenolysis occur?
in the cytoplasm
When is glycogenolysis stimulated?
when hungry by glucagon, or when stressed by epi
T/F: liver glycogen can be depleted in 12-24 hours while muscle glycogen wont even last an hour
true!
How does glycogenolysis differ between liver and muscle?
What is the function of phosphate in the cytoplasm?
can make energy or be a buffer
What is the RLE in glycogenolysis?
glycogen phosphorylase (its a transferase enzyme)
What does glycogen phosphorylase do in glycogenolysis?
uses inorganic phosphate to break alpha 1,4 o-glycosidic bonds from non-reducing ends
So when the bond breaks a G1P molecule will be let out to float in cytoplasm and this will keep going till theres only about 4 glucose residues left in a branch
What does the debranching enzyme do in glycogenolysis?
once theres 4 residues left in chain, glycogen phosphorylase stops so that the debranching enzyme can transfer 3 of the residues from the non-reducing ends of the short branch to the main branch and elongate the glucose chain
note: this will keep repeating- glycogen phosphorylase continues degrading glycogen to G1P and the debranching enzyme uses its alpha 1,6 glucosidase activity to hydrolyze the remaining residues to glucose
Also note: the debranching enzyme uses water to break the 1,6 branching bond and release a glucose residue into cytoplasm
What is the major product of glycogenolysis?
G1P because a bunch were released into cytoplasm
What is the minor product in glycogenolysis?
glucose
What is the last step of glycogenolysis?
convert G1P to glucose (liver or muscle)
What enzyme exists in the liver but not in muscle for glycogenolysis?
glucose 6 phosphatase
Glycogen storage disease type 0 is deficient in what enzyme?
glycogen synthase (this will result in no glycogen)
What are the clinical features of glycogen storage disease type 0?
glycogen synthase is deficient so there will be no glycogen
which results in:
-failure to thrive
-muscles break down constantly so theyre small and weak
-hypoglycemia
What is the deficient enzyme for glycogen storage disease type 1, also known as Von Gierke’s disease?
glucose 6 phosphatase (will result in small amounts of glycogen storage and no glucose from glycogen, all the glucose must come from food)
What are the clinical features of glycogen storage disease type 1, also known as Von Gierke’s disease?
glucose 6 phosphatase is deficient so there will be limited amounts of glycogen storage and all the glucose will have to come from food, so this results in:
-severe hypoglycemia (glucagon is secreted)
-hepatomegaly (body wants to store more)
-hyperlipidemia (lipids are secreted)
Which glycogen storage diseases have a normal glycogen structure?
-type 1, also known as Von Gierke’s disease
-type 5, also known as McArdle’s disease
-type 6, also known as Hers’ disease
Which enzyme is deficient in glycogen storage disease type 3, also known as Cori’s disease? What is the glycogen structure here?
debranching enzyme (some glycogen can change back to glucose but not all of it, so the structure will just get shorter)
What are the clinical features of glycogen storage disease type 3, also known as Cori’s disease?
glycogen debranching enzyme is deficient (some glycogen can change back to glucose but not all of it, so the structure will just get shorter)
results in:
-mild hypoglycemia
-liver enlargement
Which glycogen storage disease has nothing to do with hypoglycemia and does not affect blood glucose?
type 5, also known as McArdle’s disease (this is bc the enzyme deficient is muscle glycogen phosphorylase)
What enzyme is deficient in glycogen storage disease type 5, also known as McArdle’s disease?
muscle glycogen phosphorylase
What are the clinical features of glycogen storage disease type 5, also known as McArdle’s disease?
muscle glycogen phosphorylase is deficient, so it will result in muscle weakness when exercising for 10-20 min, but then fatigue will pass bc FAs come in to compensate
however over time it can cause acute kidney failure after build up of glycogen in myocytes and causes cells to burst
What is the treatment for glycogen storage disease type 5 (McArdle’s) and type 6 (Hers’)?
keto diet (low carbs)
Which glycogen storage disease affects liver glycogen to glucose but does not affect gluconeogenesis?
glycogen storage disease type 6, also known as Hers’
Which two glycogen storage diseases cannot breakdown glycogen?
glycogen storage disease type 5, also known as McArdle’s and type 6, also known as Hers’
type 5 is bc muscle glycogen phosphorylase is deficient
type 6 is bc hepatic glycogen phosphorylase is deficient
Which enzyme is deficient in glycogen storage disease type 6, also known as Hers’?
hepatic glycogen phosphorylase
What are the clinical features of glycogen storage disease type 6, also known as Hers’?
hepatic glycogen phosphorylase is deficient so this will result in:
-mild fasting hypoglycemia
-hepatomegaly
-cirrhosis
there will be large amounts of glucose storage!
If theres an increase in glycogenolysis, then what pathway is inhibited?
glycogenesis (and the same happens if glycogenesis is increased then glycogenolysis is inhibited)
If theres an increase in glycogenolysis then what happens at the organismal level?
-hungy
-low blood glucose
-high glucagon
-low insulin
-in rapidly contracting muscles= high epi
-stress= high epi
If theres an increase in glycogenolysis then what happens at the cellular level?
-low ATP (need energy so you cant store it anymore, it needs to be broken down)
-high AMP
-high calcium (needed for energy)
If theres an increase in glycogenesis then what happens at the organismal level?
-fed state
-high blood glucose
-high insulin
-low glucagon
-low epi
If theres an increase in glycogenesis then what happens at the cellular level?
-low AMP
-high ATP
What is the allosteric regulator for glycogen metabolism?
ATP with the RLE
What is the covalent modifier for glycogen metabolism?
hunger= increase in glucagon and epi, decrease in insulin (and the opposite for fed state)
What receptor does glucagon or epi attach to on the cell membrane?
adenylate cyclase (AC)
What is the second messenger in glycogen regulation that activates protein kinase A?
cAMP
Protein kinase A adds phosphate to 2 enzymes. What 2 enzymes get a phosphate and is this their active form or inactive form?
1) glycogen synthase- P (B form)
2) phosphorylase kinase- P (A form)
What enzyme gets activated with phosphorylase kinase in glycogen regulation?
glycogen phosphorylase-P (A form)
Which enzyme binds to glycogen to make G1P in glycogen regulation?
glycogen phosphorylase-P (A form)
Glucose enters the cell through what transporter?
GLUT 2 or 4
Which enzyme does insulin activate in glycogen regulation after entering the cell?
glycogen synthase (A form)
UDP glucose binds with what enzyme to make glycogen?
glycogen synthase
What 2 enzymes are inactive when insulin increases?
1) glycogen phosphorylase (B form)
2) phosphorylase kinase (B form)
note: both are active with P, inactive/B form is dephosphorylated!
In glycogenesis, this enzyme functions to break the chain at an alpha 1,4 linkage and forms an alpha 1,6 linkage. It adds glucose (UDP- glucose -> glucose-glycogen + UDP) residues to the terminal (non-reducing) end
glycogen synthase
Epi or glucagon first activate:
adenylate cyclase (AC)
