Anaerobic metabolism during high intensity exercise
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Anaerobic Metabolism During High Intensity Exercise. Various Roles for Anaerobic Metabolism. Essential when the demand for ATP is greater than can be provided by aerobic metabolism At the onset of high-intensity exercise At maximal O 2 consumption. The onset of High Intensity Exercise.

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Various roles for anaerobic metabolism
Various Roles for Anaerobic Metabolism

  • Essential when the demand for ATP is greater than can be provided by aerobic metabolism

  • At the onset of high-intensity exercise

  • At maximal O2 consumption


The onset of high intensity exercise
The onset of High Intensity Exercise

  • Anaerobically derived ATP may contribute 80-90 % of the total

    • O2 is in short supply until cardiovascular system can meet demands


Near maximal o 2 uptake
Near Maximal O2 Uptake

  • Near maximal O2 uptake, increases in workload elicit greater contribution from anaerobic sources

    • Since aerobic metabolism is maximal, the only other source of ATP is from non-oxidative sources


Anaerobic contribution decreases as exercise progresses
Anaerobic Contribution Decreases as Exercise Progresses

  • 30 s

    • 80 % anaerobic/20 % aerobic

  • 60-90 s

    • 45 % anaerobic/55 % aerobic

  • 120-180 s

    • 30 % anaerobic/70 % aerobic




Sources of anaerobic atp
Sources of Anaerobic ATP

  • CP or PCr degradation

  • Endogenous ATP

  • Glycolysis


Pcr degradation
PCr Degradation

Creatine PhosphoKinase

PCr + ADP + H+ ATP + Cr


Glycolysis
Glycolysis

  • Glycogen + 3 ADP + H+3 ATP + 2 lactate + 2 H+

    • Can use this relationship to determine ATP provision from glycolysis during intense exercise

    • Take a post exercise muscle biopsy and multiply [La+] by 1.5

      • Must also take into account lactate that leaves muscle


Adenosine phosphorylation
Adenosine Phosphorylation

Adenylate Kinase

2 ADP  ATP + AMP

  • creates an ATP, but also leaves an AMP


Deamination
Deamination

AMP + H+ IMP + NH4+

AMPDeaminase

  • Conversion of AMP to IMP is irreversible

  • Prevents buildup of AMP

  • in conjunction with Adenylate Kinase prevents accumulation of ADP


Atp adp ratio
[ATP]/[ADP] Ratio

  • Important because it determines free energy

  • Hi [ATP]/[ADP] allows ATP to be converted to ADP more easily

    • If this happens, there is more free energy

  • Lo [ATP]/[ADP]

    • ATPADP more difficult

    • Less free energy


How do you keep the ratio high
How do you keep the ratio high?

  • Keep making ATP from ADP

  • Also, Adenylate Kinase

    • ADP + ADP  ATP + AMP

    • But AMP can go back to ADP


Anaerobic metabolism during high intensity exercise
So

  • Deamination converts ADP to IMP and removes loitering ADPs

  • Adenylate Kinase and AMP deaminase work together to prevent AMP and ADP buildup


Why do we want to keep ratio high
Why do we want to keep ratio high?

  • To maintain control of energy flow

  • We must generate ATP, but if ADP or AMP accumulate we lose control of metabolism



Traditional serial metabolism
Traditional “Serial Metabolism”

  • PCr degradation immediate and only source of ATP supply in first 10 s

  • When PCr depleted glycolysis begins

  • No overlap of two pathways

  • Recent evidence argues against this


Pcr degradation1
PCr Degradation

  • PCr degradation is indeed instantaneous

  • Biopsies after 1.28 s of electrical stimulation show PCr breakdown


Glycolysis also instantaneous
Glycolysis Also Instantaneous

  • Elevated [La+] reported after 10 s cycling 110 % VO2max

    • Although no resting sample taken (Saltin et al., Jacobs et al.)

  • Other studies have shown [La+] after only 6 s, and PCr stores were not depleted after 6 or 10 s


  • Rates of anaerobic metabolism
    Rates of Anaerobic Metabolism

    • Anaerobic ATP must be provided at very high rate

    • Power outputs of 2-4 times VO2max can be attained for short periods

    • Even though anaerobic pathways provide less ATP per mole of substrate than oxidative pathways



    Rate continued
    Rate Continued

    • 0-10 s - ~6.0 – 9.0 mmol ATP/kg dm/s

      • Combined for PCr and glycolysis

    • 30 s – PCr ~ 1.6 and glycolysis ~4.4 mmol/kg dm/s

      • Assuming 25 % releas of lactate, ~5.8 for glycolysis



    Take home
    Take Home

    • Highest rates of ATP provision from PCr and glycolysis 0-10 s

    • From 10 – 30 s PCr stores are depleted

      • Glycolytic rate ~ 50 % of intitial 10 s

      • Glycolytic rate of ATP provision during 30s maximal exercise, 3-4 times > PCr



    Problems associated with measuring anaerobic atp provision
    Problems Associated with Measuring Anaerobic ATP Provision

    • Must take pre and post-exercise biopsies

    • Must account for lactate release from muscle

      • Arterial and venous blood sampling

      • If not, exhaustive exercise or….

      • Spriet et al. and closed circulation


    Glycolysis1
    Glycolysis

    • During intense exercise bouts ~3 min, glycolysis provides ~ 80 % total anaerobic ATP

    • Glycolysis is activated more quickly than aerobic metabolism

      • provides ATP at a higher rate

    • Can provide more ATP than PCr degradation


    Glucose from where
    Glucose from where?

    • Glucose can come from blood or glycogen

    • During short-intense exercise, primarily from glycogen

    • Uptake of glucose cannot meet glycolytic demand



    Regulation
    Regulation

    • Accumulation of G-6-P inhibits glucose phosphorlation

    • Primary points of regulation are PHOS and PFK


    Why does g 6 p inhibit glucose phosphorylation
    Why does G-6-P inhibit glucose phosphorylation?

    • Low level of glycolytic flux

      • Glycolysis isn’t moving very fast

      • Must not need G-6-P

    • That glucose can be stored as glycogen instead of being utilized for glycolysis


    Phos regulation
    PHOS regulation

    • PHOS = glycogen phosphorylase

    • The enzyme responsible for breakdown of glycogen to glucose

    • Removes one glucose at a time by adding Pi (phosphorylating)



    Phos cont d
    PHOS cont’d

    • Km of PHOS for glycogen very low (1-2 mM)

      • Means that PHOS has high affinity for glycogen

    • This means PHOS can function effectively even at low glycogen concentrations


    More phos
    More PHOS

    • Previous exercise can affect glycogenolytic rate relative to glycogen concentration

    • For example during afternoon practice following morning practice..

      • If glycogen stores are low, glycogenolysis will be reduced

      • Higher glycogen stores will result in higher relative glycogenolysis



    Pi and phos regulation
    Pi and PHOS regulation

    • Phosphorylation of PHOS (pretty redundant eh?) results in conversion of forms

      • b is inactive form

      • a is active form

      • Phosphorylation converts b form to a

    • Implications for activity???


    Anaerobic metabolism during high intensity exercise

    • At rest 10-20% of PHOS in a form

    • Conversion from b to a doesn’t necessarily mean increased glycogenolysis

    • Free Pi also needs to be available for elevated glycogenolysis to occur


    Calcium activates phos kinase
    Calcium activates PHOS kinase

    • Phosphorylation of PHOS (again) results from PHOS kinase

    • PHOS kinase activated by elevations in intracellular [Ca2+]


    Why would you want to tie phos to intracellular ca 2
    Why would you want to tie PHOS to intracellular [Ca 2+]??

    • With E/C coupling Ca2+ released from sarcoplasmic reticulum

    • Intracellular [Ca2+] elevated drastically and rapidly

    • Therefore glycogenolysis is tied closely to muscular contraction


    Acidosis hinders phos acitivity
    Acidosis hinders PHOS acitivity

    • Conversion of PHOS b to a is depressed under acidic conditions

    • After repeated bouts of interval cycling, decreased activation of glycogenolysis related to increasing muscle acidity (Spriet et al.)

    • Although activity was still reduced in a second bout 1 hour after the first, where H+ had recovered


    Phosphofructokinase pfk regulation
    Phosphofructokinase (PFK) regulation

    • Most important regulator of PFK activity is ATP

    • ATP can bind to PFK at two sites and alter its activity

    • Binds to catalytic site with high affinity

    • Can also bind to allosteric site


    Pfk cont d
    PFK cont’d

    • Binding to the allosteric site inhibits activity

    • So,… when [ATP] in the cell is high, PFK will be inhibited

      • no need for glycolysis, plenty of ATP

    • H+ can enhance ATP affinity for allosteric site

      • Provides feedback inhibition


    Some other proposed modulators
    Some other proposed modulators

    • Inhibitors

      • Citrate

      • Phosphoglycerate

      • Phophoenolpyruvate

      • Mg2+


    Anaerobic metabolism during high intensity exercise

    • Promoters

      • AMP and ADP

      • Pi

      • NH4+

      • Fructose –2,6 diphosphate


    Citrate
    Citrate

    • Probably not a major factor during short, intense exercise

    • Aerobic metabolism does not contribute greatly until later (>30 s)

    • Citrate probably does not accumulate within the 30-60 s time frame


    Promoters
    Promoters

    • ADP and AMP will accumulate rapidly at the onset of anaerobic exercise

      • Breakdown of PCr

    • H+ may be reduced at the onset of exercise

      • Removing the ATP induced inhibition


    Conclusion
    Conclusion

    • PFK regulation is obviously a complicated matter

    • During exercise many of the promoters (ADP,AMP, Pi, and NH4+) will accumulate

    • ATP will be reduced, but H+ should also rise

    • There may be unidentified factros which help maintain the awkward balance of promotion and inhibition during intense exercise