How does glucagon/epinephrine binding to cellular receptors result in release of glucose from glycogen?
It activates a G protein which phosphorylates and activate adenylyl cyclase. Adenylyl cyclase converts ATP to cAMP. cAMP binds to and activates PKA. PKA phosphorylates glycogen synthase (becomes inactive) and phosphorylase kinase (becomes active). Phosphorylase kinase catalyzes the phosphorylation of the inactive glycogen phosphorylase B form to become the active A form. Active glycogen phosphate catalyzes the phosphorylation of glycogen to release glucose-1-phosphate. Phosphoglucose isomerase turns it into glucose-6-phosphate. Glucose-6-phosphatase then makes glucose which is released into the blood.
What is cyclic about cAMP?
The phosphate group is bound to 3' carbon and 5' carbon.
How does cAMP actually activate PKA?
It binds the two regulatory subunits of PKA, releasing that the two catalytic subunits and activating them.
What happens as a result of insulin binding to the cell membrane receptor?
It activates a signaling cascade that activates a bunch of protein phosphatase-1 molecules that take phosphate off of glycogen synthase, glycogen phosphorylase, phosphorylase kinase. Insulin also activates phosphodiesterase, which hydrolyzes cAMP to AMP, turning off the 2nd messenger. Now glycogen synthase is active, glycogen phosphorylase is inactive and glycogen is being synthesized.
What key signals initiate glycogen breakdown during exercise?
Epinephrine (binding activates adenylyl cyclase, cAMP is produced, PKA is activates, phosphorylase kinase is activated and glycogen phosphorylase is activated), Ca2+ (binds Calmodulin, which activates phosphorylase kinase which phosphorylates glycogen phosphorylase b and makes it the active glycogen phosphorylase a) and AMP (binds to glycogen phosphorylase b and changes it to glycogen phosphorylase b).
A patient comes to see you because they have painful cramps whenever they begin exercising. What enzyme is deficient and what would you look for in their urine?
This patient has McCardle's Disease which is a deficiency in muscle phosphorylase. The patient may have myoglobin in the urine (rhabdomyolysis) if they are pushed too hard, this is because muscle will begin to disintegrate.
Why don't you see lactic acid accumulation in people exercising with McArdle's syndrome?
The glycolytic pathway is blocked way upstream before you even get close to lactate production.
Explain this chart regarding McArdle's disease?
ADP levels stay relatively the same in normal people because once ATP is expended, glycogen is cleaved to form more glucose to form more ATP to replenish stores. In McArdle's disease, they just can't keep up with ATP expenditure and ADP levels skyrocket.
What pathways are involved in the short term energy system in muscle?
Anaerobic glycolytic pathways
What pathways are involved in the long term energy system in muscle?
Aerobic pathways (ETC)
What pathways are involved in the intermediate term energy storage system in muscle?
What part of muscle metabolism allows you to increase your sprint from 2-3 seconds to 10 seconds?
Creatine phosphate. It donates a P to ADP to make another ATP.
How does the textbook say your body uses the different metabolic systems as exercise goes on?
1st: phosphocreatine creates more ATP. 2nd: glycogen stores last for the next two minutes. 3rd: vasodilation has occurred after about 3 minutes, tissue gets more blood flow and the aerobic system kicks in
Which muscle metabolic system produces ATP at the fastest rate during exercise (according to the textbook)?
Creatine phosphate (intermediate system). It provides the most power and is mostly used in events like the 100 meter dash.
What pushes phosphocreatine to give up its phosphate to ADP when ATP is used?
Why is AMP such a good messenger for signaling initiation of other metabolic pathways?
When ATP is hydrolyzed to ADP, AMP levels rise exponentially and make really good messengers
How do all of the components of the phosphagen system change during a sprint?
1. phosphocreatine plummets to maintain ATP levels 2. creatine, ADP, and AMP levels shoot up
How is the phosphagen system restored during rest?
Glycolysis is resynthesizing ATP right after exercise. ADP levels are brought back down and LeChatlier's principle shifts the reaction from right to left.
What is AMP's role in regulation during exercise?
It allosterically binds to and activates PFK-1, glycogen phosphorylase and AMP-protein kinase (AMP-PK).
When are phosphocreatine and glycogen truly used during exercise?
They are crucial at all intensity levels. PCr is used in 10-40 msec bursts to stimulate muscle twitch. PCr levels are restored by glycogen going to lactate. Glycogen stores are replenished by blood glucose.
Why is there a greater net loss of PCr and glycogen during more intense exercise but not in easy exercise?
In heavy exercise, there isn't enough time between muscle twitches for total PCr recovery where in light exercise there is enough time.
What type of fuel is used in higher intensity workouts? Lower intensity?
Higher = carbohydrate Lower = fat