Glycogen synthesis Flashcards
What are the primary storage sites of glycogen storage?
Liver and Skeletal muscle
What kind of glycosidic bonds are the chains in glycogen?
alpha (1-4)
What ind of bonds are the branch points in Glycogen?
alpha (1-6)
What are many glucoses bound together called?
polymer or granule ( the polymer makes up the glycogen)
When does branching occur in glycogen?
every 10 gucose
What does branching in glycogen provide to glucose?
increased solubility ad access
What is Maltose?
two glucose bonded together by an alpha(1-4) bond
What is the maximal size of a glycogen granule?
55,000 glucose molecules
How many tiers of CHO are there in glycogen?
twelve
Does the density of carbohydrates increase exponentially with each tier of glycogen?
yes
What is the characteristic of the last tier of glycogen?
contains 19,000 glucoses (or 34.6% of total glucose)
What size are most glycogen granules?
mid-sized
What kind of glycogen is synthesized more rapidly following post-exercise glycogen depletion, reaching a plateau after 24 hours?
proglycogen
What glycogen is more sensitive to dietary carbohydrate?
proglycogen
Which glycogen synthesis is sower and more consistent?
macroglycogen
What glycogen is responsible for carbohydrate loading (supercompensation)?
maroglycogen
which glycogen synthesis may last for at least 48 hours post exercise?
macroglycogen
How much glycogen can a skeletal muscle hold?
400g
How much glycogen can the liver store?
100g (the muscle stores 4x what the liver holds)
What amount of glycogen do cells store besides the muscle and liver?
relatively small quantities
Why can’t muscle release glucose?
it lacks the enzyme to release glucose
Where is glycogen stored?
the cytosol
What enzymes phosphorylate glucose?
Hexokinase (muscle)
Glucokinase (liver)
What are the steps in initiation of glycogen synthesis?
- Glucose is turned into glucose 6p
- Glucose 6p is converted into glucose 1p
- Glucose 1p is combine with UTP to form UDP glucose
- Glycogenin is used to start a chain
What is Glycogenin?
Glycogenin is a protein that starts the glycogen chain with the amino acid tyrosine
What enzyme adds the glucose to the tyrosine on Glycogenin?
Glycogen Initiator Synthase
What enzyme is utilized to transform Glucose 6P to Glucose 1P?
phosphoglucomutase
What enzyme is used to make UDP-Glucose from UTP and Glucose 1P?
UDP-Glucose Pyophosphorylase
What enzyme adds glucose onto the initiated glycogen chain? (after the first glucose is added)
Glycogen synthase
What is the storage form of carbohydrates in animals?
Glycogen
The equivalence of how many ATP are used to attach glucose to glycogen?
3 (1 from ATP, 1 from UTP and 1 from pyrophosphate)
What enzyme elongates the glycogen chain by adding alpha(1-4) bonds?
Glycogen synthase
Where is elongation of the glycogen chain occurring?
Cytosol
What enzyme adds branch points to glycogen with alpha (1-6) bonds?
Glucosyl 4:6 transferase
Where does the enzyme Glucosyl 4:6 Transferase get the glucose chains to add a branch point?
5-8 carbon chains are taken from the end and attached to another glucose molecule in the chain (of glycogen)
How are highly branched structures achieved during glycogen synthesis?
Glycogen Synthase can add (apha(1-4) bonds) glucose molecules to each end (the chain and branch point). Additionally alpha(1-6) can be added to growing chains (by 4:6 Transferase)
What are the main enzymes in glycogen regulation?
glycogen synthase (makes glycogen) glycogen phosphorylase (breaks down glycogen)
What stimulates glycogen synthase?
and in turns inhibits glycogen phosphorylase
Lots of ATP (High Energy Charge)
Lots of glucose
Insulin
Low Glycogen Levels
What inhibits glycogen synthase? (and in turn stimulates glycogen phosphorylase)
Low ATP (Low Energy Charge) Lots of ADP or AMP Low Glucose Glucagon (liver) Muscle contraction (calcium)
What will Glucagon do to glycogen synthesis?
Shuts down glycogen synthesis and activates glycogen breakdown
Catecholmines work similarly to what hormone?
Glucagon
What is the key enzyme responsible for the synthesis of glycogen?
Glycogen synthase
What is a far more potent regulator of glycogen synthase activity than insulin or muscle contraction?q
muscle glycogen concentration
When is glycogen synthase released from being bound to part of the glycogen protein complex?
when glycogen concentration decreases
What does intense exercise burn?
muscle and liver glycogen
What effect does exercise have on glycogen synthesis?
Increases GLUT4 translocation
Increase GLUT transcription-translation (more transporters)
Stimulates glycogen synthesis after exercise (free glycogen synthase)
Increases insulin sensitivity after the exercise
A single bout of resistance exercise decreased muscle glycogen by how much?
Type I fibers by 23%
Type II fibers by 42% (type 2 is responsible for hypertrophy)
When does glycogen synthesis have an initial high rate?
after intense exercise
How does glycogen synthesis change after intense exercise?
- Maximal activity during the first 30 minutes
- Rapid decline to about on fifth by 60 minutes
- reduced to about 1/9th by 120 minutes
What are the two reasons we have huge glycogen synthesis after intense exercise?
Increased glucose uptake (GLUT4s)
Increased glycogen enzyme activity (glycogen synthase)
Is the the rapid phase of glycogen synthesis insulin dependent or independent?
Insulin independed
Is the the slow phase of glycogen synthesis insulin dependent or independent?
insulin depended
When does rapid phase glycogen synthesis occur?
30-60 minutes after exercise
Occurs when muscle glycogen levels are relatively low (128-150 mmol/kg) AND carbohydrate is provided immediately after exercise
When does slow phase glycogen synthesis occur?
Follow the rapid phase (for several hours)
What must the slow phase of glycogen have?
carbohydrates available and insulin
What are the two phases of increased glucose uptake? (think GLUT4)
Insulin-independent
Insulin-dependent
When does insulin independent glucose uptake occur?
less than 3-6 hours minutes after after exercise
What is stimulated from Insulin-independent glucose uptake?
AMPK pathway
What is temporarily inhibited during Insulin-Independent Glucose uptake?
PI3K pathway (Phosphatiylinositol 3-kinase)
When does Insulin dependent glucose uptake take?
3-6 to 48 hours post-exercise
What effect will adding CHOs pos exercise do?
will increase insulin but will not have an additive effect on glycogen synthase
What happens if high glycemic carbohydrates are consumed after exercise?
the resultant hyperinsulinemia leads to only a modest increase in glycogen synthase activity.
Does exercise alone lead to a twofold increase for the first 30 minutes of recovery?
yes
Why is it better to immediately eat after exercise?
Glycogen synthesis maybe up to 45% slower if food is consumed after two hours
When do the number of glucose transporters associated with the sarcolemma return to pre-exercise concentration?
Two hours post-exercise (this is why glycogen synthesis slows down if you eat 2 hours after exercise)
What is the difference of the rates of glycogen synthesis after exercise with/without food?
w/out food = 7-12 mmol/kg dw/h
w/ food = 20-50 mmol/kg dw/h
(eating after exercise increases glycogen synthesis a Minimum of 2x)
If you do not eat after exercise where do the substrates come from for glycogen synthesis?
you catabolize amino acids to ,make glycogen
When are diminishing returns achieved for glycogen synthesis?
after 500 kcal of glucose
Can consuming more CHOs increase the rate of glycogen synthesis?
yes, glycogen synthesis will be increase up to 500kcal of glucose.
What will ingestion of protein/amino acids in combination with moderate carbohydrate intake lad to?
higher muscle glycogen synthesis rates when compared to the same amount of carbohydrates alone
When does the presence of protein/amino acids not increase glycogen synthase rates?
when total carbohydrate intake is very high
Name the order of proteins from most glycogen synthesis increase to least increase.
- Whey protein hydrosylates (5.01mg/g)
- Whey protein (4.23mg/g)
- Branch chain amino acids (3.92mg/g)
- Casein hydrosylates (2.73mg/g)
What is the difference between a trained cyclist (fit person) to an untrained individual in muscle glycogen storage?
- Muscle glycogen storage is 2 fold higher in cyclist
2. Glut4 continent is 3 times higher post exercise
How is the glycemic load calculated?
glycemic index times the grams of carbohydrates in a serving of the food.
What two things should be considered for carbohydrates in a meal?
the quantity and quality of the carbohydrates in a meal
What does a higher glycemic load mean after consumption?
a greater expected elevation in blood glucose and in the insulinogenic effect of the food
What is associated with increased risk of type 2 diabetes and coronary heart disease with respect to glycogen synthesis?
Long-term consumption of a diet with a relatively high glycemic load
During what phase are high GI (glycemic index) meals more effective at replenishing muscle glycogen?
during the second phase of recovery (slow phase)
What are the 2 benefits of low GI pre-exercise meals?
- Blood glucose levels tend to be higher in the latter phases of prolonged exercise when subjects are fed low GI compared with high GI pre-exercise meals
- Low insulin during exercise allows increased FFA concentrations
What happens to insulin after beginning to exercise?
insulin levels rapidly fall and reach low values regardless of the GI of the pre-exercise meal.
What can be used to recover from exhaustive exercises other than a meal?
glucose and Glucose/fructose (2:1 ratio) solutions
What can a low dose fructose infusion cause?
a threefold increase in net hepatic glycogen synthesis exclusively through stimulation of glycogen synthase flux
How can glucose tolerance be improved in a glucose containing meal?
by adding very low doses of fructose to the meal
How is the glycemic load calculated?
glycemic index times the grams of carbohydrates in a serving of the food.
What two things should be considered for carbohydrates in a meal?
the quantity and quality of the carbohydrates in a meal
What does a higher glycemic load mean after consumption?
a greater expected elevation in blood glucose and in the insulinogenic effect of the food
What is associated with increased risk of type 2 diabetes and coronary heart disease with respect to glycogen synthesis?
Long-term consumption of a diet with a relatively high glycemic load
During what phase are high GI (glycemic index) meals more effective at replenishing muscle glycogen?
during the second phase of recovery (slow phase)
What are the 2 benefits of low GI pre-exercise meals?
- Blood glucose levels tend to be higher in the latter phases of prolonged exercise when subjects are fed low GI compared with high GI pre-exercise meals
- Low insulin during exercise allows increased FFA concentrations
What happens to insulin after beginning to exercise?
insulin levels rapidly fall and reach low values regardless of the GI of the pre-exercise meal.
What can be used to recover from exhaustive exercises other than a meal?
glucose and Glucose/fructose (2:1 ratio) solutions
What can a low dose fructose infusion cause?
a threefold increase in net hepatic glycogen synthesis exclusively through stimulation of glycogen synthase flux
How can glucose tolerance be improved in a glucose containing meal?
by adding very low doses of fructose to the meal
What has a higher Km, glucokinase or hexokinase?
Glucokinase
Is glucokinase inhibited by Glucose 6 phosphate?
No
Small amounts of fructose cause the release of what from a regulatory protein?
glucokinase
What causes glucokinase to be inhibited by F6P?
F6P binds to the regulatory protein
What happens when F1P binds to the regulatory protein?
Glucokinase is set free and is activated
In the fasted state what is the main endogenous source of glucose?
the Liver is the main endogenous source of glucose (2 mg/kg/min)
What occurs following glucose consumption in Liver glucose metabolism?
Liver consumes glucose
Liver removes approximately one-third of an oral carbohydrate load
Will insulin cause the liver to take in glucose during normal blood glucose range?
Nope
Where is the primary site of fructose disposal?
Liver
How much fructose is extracted by the liver?
50% on the first pass
70% total
What enzymes are highly expressed in the liver that are essential for fructose metabolism?
Fructokinase
Triokinase
Does fructose have a benefit for muscle glycogen synthesis?
no :(
Does fructose benefit liver glycogen synthesis?
yes, low doses increase liver glycogen synthesis
Why are high levels of fructose not good?
Liver has a high uptake
Increased Fat, Lactate and Glycerol formation
What are the enzymes for Glycogen synthesis?
Hexokinas and glucokinase phosphoglucomutase UDP Glucose Pyrophorylase pyrophosphatase Glycogen initiator synthase Glycogen synthase Glucosyl 4:6 Transferase
What enzymes are used for glycogen breakdown?
Glycogen phosphorylase
phosphoglucomutase
Glucosyl (4:4) Transferase
amylo-alpha-(1,6)-glucosidase
What conditions stimulate glycogen synthesis?
High blood glucose Insulin Fructose (in liver) Low glycogen content High Energy Charge ATP
What stimulates Glycogen breakdown?
Low blood glucose (in liver) Glucagon (in liver) Low energy charge ADP, AMP Calcium (muscle contraction)
