Glycogen Flashcards
Glucose is preferred energy source for…
Brain and RBC
Where is glucose obtained from?
Diet
GNG
Glycogen storage
Dietary intake of glucose
- sporadic
- dependent on diet content
- not always a reliable source
GNG glucose supply
- can provide sustained synthesis of glucose
- is somewhat slow in responding to falling blood glucose levels
Glycogen storage supply of glucose
-mechanisms for storing a supply of glucose in a rapidly metabolized form
Places you can find glycogen
- virtually any cell is capable of containing glycogen, but it VERY SMALL AMOUNTS
- Skeletal muscle(uses it as own fuel source, cannot exit into the blood stream)
- Liver(releases it into the blood to maintain blood glucose levels)
Glycogen distribution in liver
- 100g
- 10% of the fresh weight of an adult well fed liver
Glycogen distribution in skeletal muscle
- 400g
- 1-2% of the fresh weight of resting muscle
Water and glycogen
- glycogen storage is associated with water storage
- water has 5X the weight of glycogen
- your weight can vary significantly based on the amount of glycogen you have stored
degradation of glucose (liver and muscle cells)
- liver: when not getting glucose from diet, glycogen is degraded to glucose and released from liver and kidney(very small amount from kidney)
- muscle:in exercising muscle, glycogen is degraded to provide that tissue with energy
- glycogen serves as a glucose source in the gap between the fall of glucose levels after a meal and the onset of GNG(few hours)
Glycogen structure
- HIGHLY branched polysaccharide made EXCLUSIVELY from alpha D glucose
- 10-40,000 glucose molecules per one glycogen
- primary bond is alpha 1-4 linkage(linear)
- every 8-10 glucosyl residues, there is a branch with alpha 1-6 linkage
Discrete cytoplasmic granules
- beta particles
- associated with ALL the enzymes necessary for degradation and synthesis of glycogen
- all enzymes are associated all the time
Step 1: Synthesis of Uridine diphosphate glucose
- alpha D glucose —>glucose 6P SUPER FAST
- glucose 6P—>Glucose 1P
- UTP—->UDP
- UDP glucose (highly energetic carrier to transport glucose)
- if sufficient energy, it will save glucose for later
- highly exergonic(drives the rest of synthesis)
Step 2: Synthesis of a primer to initiate glycogen Synthesis
- glycogen synthase CANNOT add UDP-glucose to a single glucose molecule, it can only ELONGATE primers
- no primers? glycogenin serves as primer
Glycogenin
- protein that can serve as primer if there are no primers available
- specific tyrosine residue serves as attachment point for glycogen synthesis
- catalyzes(acts as enzyme) the attachment reaction and the attachment for the next few UDP-glucose molecules via 1-4 glycosidic bonds
- after it binds 4, its a primer so glycogen synthase can take over
Step 3: elongation of glycogen chains
Enzyme: glycogen synthase
- elongates existing primers
- transfers UDP-glucose to NON REDUCING end of primer
- forms alpha 1-4 bonds ONLY between UDP and primer
- rate limiting
Step 4: Formation of branches
Enzyme: branching enzyme
- removes chain of 6-8 glucosyl residues from the end of glycogen chain(breaks 1-4 bond)
- attaches it to non terminal glucosyl residue by 1-6 bond
- functions as 4:6 transferase
Why are branches important?
- increases solubility of glycogen
2. increases surface area to make more reducing ends for faster degradation and synthesis
Glycogenolysis
-degradation of glycogen
-NOT A REVERSAL OF GLYCOGENESIS
-gets its own set of enzymes(still on beta particles)
-4 step pathway
Shortening of chain
removal of branches
glucose1P—->glucose 6P
glucose 6p—->glucose(ONLY IN LIVER)
Step 1 of degradation: shortening of chain
Enzyme: glycogen phosphorylase
- rate limiting step
- tissue specific isoforms for liver, muscle, and brain
- cleaves alpha 1-4 bonds from ends of chains
- uses INORGANIC PI to cleave AND attach itself to glucose
- yields glucose 1P
- stops when chain is only 4 glucosyl units from branch point
- requires PLP(vitamin B6) as coenzyme
Limit dextrins
- branch point
- once it is down to 4 units, it does not fit in active site of enzyme anymore, so shortening of chains done
Step 2 of degradation: removal of branches
Enzyme: debranching enzyme
- single protein, 2 activities
4: 4 transferase activity: removes 3 of the 4 glucosyl residues by breaking 1-4 bond and transfers the to end of another chain by 1-4 bond
1:6 glucosidase activity: removes remaining residue attached by 1-6 bond and creates free glucose!
Step 3 of degradation: Conversion of Glucose 1P to glucose 6P
Enzyme: phosphoglucomutase
- forms intermediate glucose 1-6 bisphosphate
- activated by glucose 1-6 bisphosphate
- ser-phosphorylation allows to put another on, then release ser and you only have one P
Step 4 of degradation: glucose 6P—> glucose
Enzyme: Glucose 6-phosphatase
- liver and kidney
- sometimes in beta pancreatic cells, but much less
- ER transmembrane with active site facing ER lumen
- complex (3 transporters and catalytic subunit)
- G6PT1,2,3 and G6Pase alpha or beta
degradation in lysosomes
Enzyme: lysosomal alpha 1-4 glucosidase
- housekeeping gene(always expressed)
- regulated at the level of protein expression
- optimal pH=4.5(acidic)
- only 1-3% of glycogen
- purpose of this pathway is not understood, but when it is missing, it is no bueno
regulation of glycogenesis and glycogenolysis in liver
- glycogenesis is up in well fed state
- glycogenolysis is up during fasting
Regulation of glycogenesis and glycogenolysis in muscles
- glycogenesis is up at rest
- glycogenolysis is up during exercise
Hormonal regulation
to meet the needs of the body as a whole
Allosteric regulation
to meed the needs of a particular tissue only
glycogen phosphorylase in liver
- activated by epinephrine and glucagon
- inactivated by insulin
- inactivated by glucose6P,glucose, and ATP
glycogen phosphorylase in muscle
- activated by epinephrine, high AMP and Ca2+
- inhibited by insulin and high ATP and Glucose 6P
Glycogen synthase in liver and muscles
- both activated by insulin and Glucose 6P
- muscle inhibited by epinephrine
- liver inhibited by epinephrine and glucagon
Von Gierke
-deficient: glucose 6-phosphatase
-Location: liver and kidnet
-Features: fasting, lactic acidosis, hypoglycemia, glucose cannot leave cell(goes to synthesize fats)
Structure:normal
Pompe
Deficient: Lysosomal alpha 1-4 glucosidase
- Location: can effect all cells
- Features: muscle weakness, death at 2, cardiomegaly
- Structure: glycogen like material in inclusions
Cori
- Deficient: Branching enzyme
- location: yea idk
- Features: mild hyperglycemia, liver enlargement
- Structure: short outer branches, single glucose residue at outer branch
Andersen
Deficient: Branching enzyme (super rare)
- Location: synthesis of glycogen
- Features: infantile hypotonia, cirrhosis, death at 2
- Structure: very few branches, less soluble
Mcardle
- Deficiency: Muscle glycogen phosphorylase
- Location:muscles only.(liver isoform is still gucci)
- Features: muscle cramps, weakness, myoglobinuria
- Structure: normal
Hers
- Deficiency: hepatic glycogen phosphorylase
- Location: liver only(muscle isoform is still gucci)
- Structure: Normal
