·         Metabolic plasticity (can use any substrate provided – will use the one that’s most available)

·          Mitochondrial enrichment ( a lot of mitochondria and ATP demand can change in an instant)

·          Major site of insulin responsive glucose uptake/metabolism (GLUT4)

·          Muscle specific isoforms of several metabolic enzymes

Explain the creatine/phosphate pool

• The most immediately available energy source for ATP resynthesis is creatine phosphate.
• Stores of creatine phosphate are much higher in skeletal muscle than other places
• At rest ATP donates phosphate to creatinine phosphate pool; during exercise muscle uses ATP from creatine phosphate pool

How is ATP necessary for muscle contraction and relaxation? 

ATP must bind to myosin before myosin can bind to actin myofilament to form crossbridge for muscle contraction.  Another ATP is needed for muscle relaxation.  

What are three NADH producing steps of the TCA cycle?

a)      Isocitrate dehydrogenase (isocitrate à a-ketoglutarate)

b)      A-ketoglutarate dehydrogenase  (a-ketoglutarate à succinyl-CoA)

c)       Malate dehydrogenase (malate à OAA)

Point is TCA cycle is critical source for electrons from NADH/FADH that drive ATP synthesis

1)      Immediate: Creatine phosphate – via creatine phosphokinase

2)      Anaerobic and aerobic (not-trained) : Muscle glycogen – via glycolysis

3)      Aerobic (trained muscle): Muscle TAG – via TAG breakdown (HSL)and oxidative phosphorylation)

          Why does aerobic oxidation produce more ATP than anaerobic? 

Because it can go through the TCA cycle and electrons can be completely oxidized.

In glycolysis only the NADH produced goes to ETC to make ATP.  In aerobic, the reducing equivalents NADH and FADH made from the TCA cycle goes to the ETC to make ATP which produces much more energy.  

 What energy systems are used for each phase of exercise?  

a)      Immediate system (ATP-CP):  10-30 sec

b)      Short-term (glycolytic) system:  30 sec – 1 mim

c)       Long-term (aerobic) system:  1+ minutes

What happens to oxygen as exercise intensity increases?  

Oxygen consumption increases at a linear rate but at some point it is maxed out (can’t deliver and metabolize more oxygen) this is anaerobic threshold now only choice left is to use the anaerobic system now blood lactate levels begin to rise. 

 How does glucose get transported out of the liver? 

It must be converted to glucose-6-phosphate via glucose-6-phosphatase 

a)      Liver makes glucose from glycogen and from GNG; glucose goes to muscle and brain (absolutely crucial for brain)

b)      FA are also crucial – they mostly come from lipolysis of adipose tissue – lipolysis is activated by stress hormones during exercise (HSL) – muscle uses FA so that brain  can use glucose

c)       Glucose homeostasis during exercise is very similar to maintenance of homeostasis during fasting/starvation

d)      Even though muscle can’t undergo GNG, it is important because it feeds the liver GNG precursors:  lactate, alanine 

1)      What are the three major factors that influence substrate utilization during exercise?  

• Red/slow twitch
• Lots of mitochondria 
• Insulin sensitive
• Fatigue resistant (can't produce lactate)
• Low capacity for glycolytic ATP production so low force
• Lots of oxidative enzymes, little glycolytic enzymes

Which fibers are used during different phases of exercise?

Type 1 are used during lowest intensity, then type IIA then type IIB/X. Type IIA are used more in trained athletes. Higher power = higher rates of ATP production. 

Type 1 have lots of mitochondria – so they can use a lot of FA – so at a lower intensity you’ll be using mostly FA. Type 2X – almost completely dependent on glucose – so at a higher intensity you’re using mostly carbohydrates. 

    How is RER calculated? 

Amount of CO2 produced for amount of oxygen consumed (FA require more oxygen than carbs for a given amount of ATP) High RER = if they are using entirely glucose the RER will be 1, if it’s using FA it will be about .7

    How does the rate of glycogen depletion vary during exercise intensity? How does this effect what you should eat before exercise? 

Glycogen depletion is slow during low intensity exercise and fast during high intensity exercise.  If you’re doing something high intensity or of a super long duration, it makes sense to carb load before exercise, it doesn’t make sense for low-intensity or shorter exercise. 

How do fatty acids fuel the TCA cycle?  

Beta-oxidation produces acetyl-CoA but FA need other substrates to make reducing equivalents from TCA cycle to make fuel for exercise.

Choices

1)      Pyruvate can be rerouted to pyruvate carboxylase so it is converted to OAA

2)      If glucose becomes limiting (can’t make pyruvate) AA from protein can be converted to TCA intermediates via transamination. Transaminases allow AA to be converted to fuel TCA cycle – however glucose is preferred substrate

Moral:  Even when using FA for energy you still need glucose to fuel exercise 

How does muscle choose between glucose and FA for fuel? 

·         When glucose is plentiful – plenty of TCA intermediates, (citrate, acetyl-Coa, malonyl-CoA ) inhibits CPT-1 cuz there’s plenty of glucose so we don’t need to oxidize fat

·         *other scenario – muscle contraction – AMP increase – AMPK plates ACC and turns off glucose pathways and CPT-1 is activated – FA are broken down to acetyl-CoA, if plenty of fat feeding TCA cycle then acetyl-CoA levels rise and feedback inhibits PDH (pdhkinase p’lates PDH and inactivates)

·         As intensity increases further – AMP signals will increase glucose uptake, glycolytic rate in order to keep feeding the cycle 

What specific adaptations happen to muscle during training?

 1) Increased capacity for oxidative ATP production 
2) and increased capacity to use FA as a substrate

3) Increase in: Mitochondrial biogenesis; β-oxidation enzymes;TCA cycle enzymes; Electron transport chain

          How does training affect substrate utilization based on exercise intensity? 

With exercise training there is a shift to rely more on FA for fuel than carbohydrates. We are shifting the point of the anaerobic threshold so at any given intensity there is a higher contribution of fat – this is why there are increased FA stores in trained muscles

What’s the difference between red and white muscle?

 ·         Red muscle = more lipid droplet; With training, white muscle will get more lipids (substrates are changing)

·         In many cases lipid droplets are surrounded by mitochondria – so the lipid droplets are providing substrate to the mitochondria 

1         What is one basic theory for how exercise protects against chronic disease? 

Exercise consumes extra fuel that would otherwise wreak havoc in body – increased inflammation in adipose/other tissue, change in type of adipokines (hormones released – diet has huge effect on that). Protects against nutrient-induced metabolic stress.  

1)      What are the 3 categories of stimuli that mediate adaptive responses to exercise? 

·         Muscle contraction/muscle signaling (calcium/CAMK)

·         Neurohormonal signals (catchecolemines, cAMP)

·         Nutrient delivery/metabolism (FA,energy state, acute/long-term metabolic regulation)

Complex – many inputs and many signals that are being generated, this is important when we think about if it’s practical to mimic exercise through drugs 

What are the PGC-1a Targets

PGC-1a is activated during exercise and has all of these important effects

·         NRF (nuclear respiratory factor)  mitochondrial biogenesis

·          ERRa (estrogen related receptor-a) oxidative phosphorylation

·          PPARs ® lipid metabolism

·         MEF2 ® glucose metabolism