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What are the 5 energy sources?
ATP stores
Creatine Phosphate system
Carbohydrates
Fat metabolism
Protein metabolism
Where are ATP and CP stores located?
Skeletal muscle (sarcoplasm)
What is the time frame for ATP stores?
1-3 sec
How can ATP stores be increased and what is the result?
Increase muscle mass = results in increased strength and power
Where does the ATP for ATP stores come from?
General ATP floating in cytosol from pathways
What is the time frame for anaerobic breakdown of carbohydrates (glycolysis)?
30 sec -3 min
Under what conditions can lactate act as an intermediate fuel source?
Under aerobic conditions
What problems are associated with lactate accumulation?
- disruption of the contractile process
(Contractions become painful)
- inhibition of uptake of blood glucose and fat (under extreme conditions)
Why is plasma glucose one of the most precisely regulated variables?
Glucose is primary fuel for brain
What are normal fasting glucose levels?
70-100 mg/dL
(<6.1 mmole/ L)
What is the metabolic pathway for the breakdown of glucose?
Glycolysis
What factors does the uptake of glucose from cells depend on?
-type of tissue
-levels of glucose in blood and tissue
- presence of insulin
- physiological status of tissue
Why is muscle the primary glucose disposal unit?
Muscle is the largest tissue containing enzymes for glycolysis
Why doesn't contracting muscle require insulin despite most tissues requiring insulin?
Contracting muscle has an insulin like effect
Why does the liver consume large amounts of glucose?
The liver is gluconeogenic (takes in glucose to store as glycogen)
Where are ALL glycolytic enzymes located?
In the cytoplasm of the cell
Why is the glycolytic pathway called anaerobic?
Oxygen is not required
What are the rate limiting steps of glycolysis?
1, 3, 10
What are the rate limiting enzymes of glycolysis?
hexokinase (HK) phosphofructokinase (PFK), pyruvate kinase (PK)
What activates (turns up) ATP stores?
- muscle contractions (ex. Cross bridge cycling)
What inhibits (turns down) ATP stores?
Cessation of muscle contraction
What activates (turns up) CP system?
- less ATP (more ADP/AMP)
- increase Ca2+ in sarcoplasm
"Increased Ca2+ in sarcoplasm is a marker for increased muscle contraction"
What inhibits (turns down) CP system?
- more ATP (less ADP/AMP)
"Could be caused by decrease in muscle contractions or ATP made by other systems
- decrease Ca2+ in sarcoplasm
"Muscle contractions decreased"
What activates anaerobic breakdown carbs?
- less ATP (more ADP/AMP)
- decreased CP in sarcoplasm
-increase in epinephrine in blood
What inhibits anaerobic breakdown carbs?
- more ATP (less ADP/AMP)
"Due to decreased muscle contractions or ATP made from other systems"
-increase in CP in cytosol
-increase blood lactate
What activates aerobic breakdown carbs?
Aerobic carbohydrate breakdown is activated by:
Lower ATP levels (↑ ADP and AMP)
Decreased creatine phosphate (CP) in the sarcoplasm
Increased epinephrine in the blood
Increased insulin in the blood
These signals tell the muscle that more energy (ATP) is needed, stimulating aerobic metabolism of carbohydrates.
What inhibits aerobic breakdown carbs?
- more ATP (less ADP/AMP)
- increase CP in sarcoplasm
- increase blood lactate
-decrease epinephrine in blood
- decrease insulin in blood
What activates aerobic breakdown fats?
- less ATP (more ADP/AMP)
- decrease CP in sarcoplasm
- decrease insulin in the blood
- increase caffeine in the blood
-increase citrate in the muscle
-increase epinephrine in blood
What inhibits aerobic breakdown fats?
Aerobic fat breakdown is inhibited by:
High ATP levels (↓ ADP/AMP)
↑ increased creatine phosphate (CP) in the sarcoplasm
↑ increased insulin in the blood
↑ Increased blood lactate
↓ Decreased epinephrine in the blood
These signals indicate that energy demand is low or that the body is relying more on carbohydrates for fuel instead of fats.
What are 4 recommended strategies for improving performance of anaerobic glycolysis?
1. Improve anaerobic capacity of specific muscles
2. Improve lactate tolerance (interval type training)
3. Improve aerobic capacity of other muscle groups (cross training)
4. "Soda loading" is not recommended because of the many potential adverse side effects
What is the order of muscle fibers with the greatest oxidative capacity to convert lactate back to pyruvate?
Order (highest → lowest):
Cardiac (CO) → Type I (SO) → Type IIa (FOG) → Type IIb (FG)
What are fuel problems associated with activity lasting 40 to 50 min?
- high risk of muscle glycogen depletion
- moderate risk of liver glycogen depletion
- moderate risk of hypoglycemia
What are strategies for avoiding glycogen depletion and hypoglycemia?
- high carbohydrate diet and pre-event meal
- carb loading
What is carb loading and what does it result in?
Carb loading is when athletes eat a lot of carbohydrates for a few days before a long event (like a marathon) to fill up their muscles with extra glycogen — the main fuel for exercise. This gives muscles more stored energy. Helps you go longer before getting tired
How long can your body keep using carbs (glucose/glycogen) as its main fuel source during aerobic exercise?
Carbs can fuel aerobic activity for up to about 40 minutes naturally.
With carb loading, you can stretch that to ~150 minutes.
With carb feeding during exercise, you can go even longer than 150 minutes.
What is fat dependent activity?
Fat-dependent activity refers to exercise or metabolic activity where fat is the main energy source.
Occurs mainly at rest (basal metabolic rate).
Fat use increases the longer an activity lasts.
Fat contribution is highest during low-intensity exercise.
What is the end result of glycolysis?
- 2 ATP
- 2 NADH
- 2 Pyruvate
What is the PRIMARY rate limiting enzyme in glycolysis?
Phosphofructokinase (PFK)
What are the three rate limiting enzymes in glycolysis?
- hexokinase (HK)
- phosphofructokinase (PFK)
- pyruvate kinase (PK)
What is step one of glycolysis?
Glucose → Glucose-6-phosphate (via Hexokinase)
Reaction: ATP → ADP + H⁺
Requires ATP
This step phosphorylates glucose, trapping it inside the cell and committing it to glycolysis.
What is step 3 of glycolysis?
Fructose-6-phosphate (F6P) → Fructose-1,6-bisphosphate (F1,6, BP) (via Phosphofructokinase (PFK))
ATP → ADP + H⁺
Requires ATP (energy investment phase)
Irreversible step
What two steps in glycolysis are required to use ATP
Step 1 and step 3
What steps of glycolysis produce ATP?
Step 7 and Step 10
(2 ATP generated each step)
What is step 6 of glycolysis?
Glyceraldehyde-3-phosphate (G3P) → 1,3-bisphosphoglycerate (1,3-BPG) (via Glyceraldehyde-3-phosphate dehydrogenase)
Reaction: NAD⁺ + Pi → NADH + H⁺ + H₂O
2 NADH are produced (one per G3P molecule)
What step in glycolysis produces NADH?
Step 6 produces 2 NADH
What is step 10 of glycolysis?
Phosphoenolpyruvate (PEP) → Pyruvate (via Pyruvate kinase)
Reaction: ADP + Pi → ATP
This is the final step of glycolysis and one of the irreversible reactions that produces ATP.
Why is lactate production important?
The conversion of pyruvate to lactate by LDH oxidizes NADH to NAD to be recycled in step 6
- important to keep glycolytic pathway from backing up
How does a decrease in LDH activity affect glycolysis?
A decrease in LDH activity means less pyruvate is converted to lactate, so:
More pyruvate remains available for the Krebs cycle.
Less NADH is oxidized to NAD⁺ in the cytosol.
More NADH is instead shuttled into the mitochondria for aerobic ATP production.
Under what conditions is NAD recycled to step 6 of glycolysis?
NAD⁺ is recycled the most during anaerobic glycolysis when oxygen is limited and ATP demand is high, letting glycolysis keep producing energy even without oxidative phosphorylation.
(Some is always being recycled; nothing ever turns off)
What are the two types of LDH isoenzymes and what 5 isoenzymes do they form?
- M type (muscle) H type (Heart)
- M4 (muscle) M3H1, M2H2, M1H3, H4 (heart)
Why is lactate not a dead end byproduct?
- lactate can be taken up by the liver and turned back into glucose
- lactate can be taken up by the heart or by the slow twitch muscle fibers and converted to pyruvate to be used to generate ATP in krebs cycle
What kind of tissue is the heart?
Aerobic tissue
How do levels of lactate production compare between a trained and sedentary person?
A trained person is much more efficient at clearing lactate
Why is an endurance trained person more efficient at clearing lactate?
A trained person has more mitochondria
What happens to the 2 NADH produced in glycolysis during aerobic breakdown of carbs?
Most of the NADH is shuttled to ETC
Where does the M type of LDH predominate?
In anaerobic tissue such as muscle and liver
Where does H type LDH predominate?
aerobic tissue such as the heart
What happens to lactate produced in fast twitch muscle fibers?
- lactate is kicked out into blood and picked up by the liver or slow twitch muscle fibers
The build up of what leads to muscle soreness?
lactic acid
NOT LACTATE
What is the primary rate limiting step of glycolysis?
Step 3
When looking at effects of exercise training on the glycolytic pathway what enzyme should you think of?
PFK
Enzymes involved in metabolism are under what type of control?
Allosteric control
What is PFK activated by?
ADP, AMP, F-6-P
(High ADP, AMP indicates LOW ATP)
(High F6P is a substrate which suggests there is lots of glucose coming in)
What is PFK inhibited by?
ATP, citrate, fatty acids
(High levels of citrate suggests fat metabolism is occurring and we should save glycogen stores)
What happens to the pyruvate formed by glycolysis under aerobic conditions vs anaerobic conditions?
Aerobic: pyruvate is further oxidized by the Krebs cycle
Anaerobic: pyruvate is converted to lactate
How can a rise in ATP affect PFK activity?
A rise in ATP can lower PFK activity to 15% of its original level
Why does an endurance trained athlete want to turn down glycolysis?
An endurance trained athlete wants to burn fat for as long as possible to spare glycogen stores and blood glucose levels
What are reasons ATP may be high in regard to glycolysis?
- low metabolic demand
- burning fats
What happens to the back up of glucose when glycolysis is turned down?
- glucose is stored as glycogen in the cytoplasm
An anaerobic athlete wants to regulate the glycolytic pathway while an endurance trained athlete wants to....
Turn DOWN the glycolytic pathway
What is the OVERALL reaction of glycolysis?
Glucose + 2 NAD⁺ + 2 Pi + 2 ADP → 2 Pyruvate + 2 NADH + 2 H⁺ + 2 ATP + 2 H₂O
What are the two major storage tissues for glycogen?
Liver and muscle
What is muscle glycogen used for?
Synthesis of ATP during muscle contraction
What provides up to 80% of the glucosyl residues for glycolysis?
Muscle glycogen stores
What is liver glycogen used for?
Maintaining blood glucose levels during periods of low blood glucose
Why is the highly branched structure of glycogen physiologically significant?
It allows for rapid degradation of glycogen through the release of glucose units at the end of each branch
(Important because glycogen needs to easibly accessible)
What are three reasons it's important any that glycogen's beaches structure makes it easily accessible?
- muscle cannot mobilize fat as quickly as glycogen
- fat cannot be metabolized anaerobically
- fat metabolism cannot maintain blood glucose levels at rest or during exercise
What are the three enzymes required by glycogenolysis?
- glycogen phosphorylase
- glycogen debranching enzyme
- phosphoglucomuctase
Why is the rate of glycogen breakdown linked to muscle contraction?
Because muscle contraction increases intracellular Ca²⁺, which activates glycogen phosphorylase, the enzyme that breaks down glycogen.
What is the role of glycogen phosphorylase in glycogenolysis?
Glycogen + Pi → Glycogen (n−1) + Glucose-1-phosphate (G1P)
Glycogen phosphorylase cleaves the α(1→4) glycosidic bonds in glycogen, releasing glucose-1-phosphate (G1P) from the nonreducing ends of the glycogen chain.
Removes one glucose unit at a time.
What activates glycogen phosphorylase?
- High AMP/ADP (low ATP)
- increased intracellular Ca2+ (muscle contraction)
- increased cAMP (also related to muscle contraction)
What inhibits glycogen phosphorylase?
-ATP
-G6P
-glucose
What is the function of glycogen debranching enzyme in glycogenolysis?
Cleaves the branched 1-6 bond releasing a free molecule of glucose
This allows glycogen phosphorylase to continue
What is the function of phosphoglucomutase in glycogenolysis?
Converts G1P to G6P
- in muscle G6P enters glycolytic pathway
- in liver G6P is hydrolyzed to glucose
Why is muscle NOT a gluconeogenic tissue?
Muscle does not have Glucose-6-phosphatase
What tissues have glucose-6-phosphatase?
liver and kidney
(NOT muscle)
What is the function of glucose-6-phosphatase?
Converts G6P to glucose
In muscle why must G6P go through the glycolytic pathway instead of being converted to glucose and stored as glycogen?
Muscle lacks glucose-6-phosphatase and therefore is not able to convert G6P back to glucose
What glucose transporter is non-insulated mediated?
GLUT 1
What glucose transporter is insulin dependent?
GLUT 4
In resting muscle what glucose transporter does most of the glucose enter through?
GLUT 1
Where do GLUT 1 transporters reside?
PERMANENTLY in plasma membrane
Where do GLUT 4 transporters reside?
Most are stored in intracellular vesicles and are translocated to the plasma membrane when stimulated by exercise or insulin
What stimulates the translocation of GLUT 4 to cell membrane?
Insulin or exercise
How does most glucose enter the cell when glucose and insulin levels are high?
GLUT 4
How are GLUT 1 transporters affected by exercise?
Exercise has no affect on number of GLUT 1 as they are permanently embedded in cell membrane
An increase in muscle mass can increase amount of GLUT 1 due to the increase in surface area
How can the number of GLUT 1 a person has be increased?
Increase muscle mass which increases surface area of cells and therefore amount of GLUT 1 embedded in membrane
(Increased muscle mass has no affect on GLUT 4)
How does glucose enter the cell through transporters (both GLUT1 and GLUT4)
Simple diffusion : [high] to [low]
Why is it important that we have both GLUT 1 and GLUT 4 receptors?
Helps to maintain blood glucose levels
(If GLUT 4 were always in cell membrane blood sugar would PLUMMET and if we only had GLUT 1 we wouldn't be able to clear enough glucose after a meal and blood sugar would be too high)
How does muscle contraction affect GLUT 4?
It has an insulin-like effect
by increasing the translocation of GLUT 4 to the plasma membrane