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. - PowerPoint PPT Presentation

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  • Anaerobic Metabolism During High Intensity Exercise

  • Various Roles for Anaerobic MetabolismEssential when the demand for ATP is greater than can be provided by aerobic metabolismAt the onset of high-intensity exerciseAt maximal O2 consumption

  • The onset of High Intensity ExerciseAnaerobically derived ATP may contribute 80-90 % of the totalO2 is in short supply until cardiovascular system can meet demands

  • Near Maximal O2 UptakeNear maximal O2 uptake, increases in workload elicit greater contribution from anaerobic sourcesSince aerobic metabolism is maximal, the only other source of ATP is from non-oxidative sources

  • Anaerobic Contribution Decreases as Exercise Progresses30 s80 % anaerobic/20 % aerobic60-90 s45 % anaerobic/55 % aerobic120-180 s 30 % anaerobic/70 % aerobic

  • Insert fig 1.2

  • Insert Fig 1.1

  • Sources of Anaerobic ATPCP or PCr degradation

    Endogenous ATP

    Glycolysis

  • PCr Degradation

    Creatine PhosphoKinase PCr + ADP + H+ ATP + Cr

  • Glycolysis

    Glycogen + 3 ADP + H+3 ATP + 2 lactate + 2 H+Can use this relationship to determine ATP provision from glycolysis during intense exerciseTake a post exercise muscle biopsy and multiply [La+] by 1.5Must also take into account lactate that leaves muscle

  • Adenosine Phosphorylation

    Adenylate Kinase2 ADP ATP + AMPcreates an ATP, but also leaves an AMP

  • Deamination

    AMP + H+ IMP + NH4+AMP DeaminaseConversion of AMP to IMP is irreversiblePrevents buildup of AMPin conjunction with Adenylate Kinase prevents accumulation of ADP

  • [ATP]/[ADP] RatioImportant because it determines free energyHi [ATP]/[ADP] allows ATP to be converted to ADP more easilyIf this happens, there is more free energyLo [ATP]/[ADP] ATPADP more difficultLess free energy

  • How do you keep the ratio high?Keep making ATP from ADPAlso, Adenylate Kinase ADP + ADP ATP + AMPBut AMP can go back to ADP

  • SoDeamination converts ADP to IMP and removes loitering ADPsAdenylate Kinase and AMP deaminase work together to prevent AMP and ADP buildup

  • Why do we want to keep ratio high?To maintain control of energy flowWe must generate ATP, but if ADP or AMP accumulate we lose control of metabolism

  • Timing of Anaerobic Pathways

  • Traditional Serial MetabolismPCr degradation immediate and only source of ATP supply in first 10 sWhen PCr depleted glycolysis beginsNo overlap of two pathwaysRecent evidence argues against this

  • PCr DegradationPCr degradation is indeed instantaneousBiopsies after 1.28 s of electrical stimulation show PCr breakdown

  • Glycolysis Also InstantaneousElevated [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 MetabolismAnaerobic ATP must be provided at very high ratePower outputs of 2-4 times VO2max can be attained for short periodsEven though anaerobic pathways provide less ATP per mole of substrate than oxidative pathways

  • Insert Table 1.2

  • Rate Continued0-10 s - ~6.0 9.0 mmol ATP/kg dm/sCombined for PCr and glycolysis30 s PCr ~ 1.6 and glycolysis ~4.4 mmol/kg dm/sAssuming 25 % releas of lactate, ~5.8 for glycolysis

  • Insert fig 1.4

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

  • Direct Measurement of Anaerobic ATP ProvisionInsert Table 1.3

  • Problems Associated with Measuring Anaerobic ATP ProvisionMust take pre and post-exercise biopsiesMust account for lactate release from muscleArterial and venous blood samplingIf not, exhaustive exercise or.Spriet et al. and closed circulation

  • GlycolysisDuring intense exercise bouts ~3 min, glycolysis provides ~ 80 % total anaerobic ATPGlycolysis is activated more quickly than aerobic metabolism provides ATP at a higher rateCan provide more ATP than PCr degradation

  • Glucose from where?Glucose can come from blood or glycogenDuring short-intense exercise, primarily from glycogenUptake of glucose cannot meet glycolytic demand

  • GLUT proteins

  • RegulationAccumulation of G-6-P inhibits glucose phosphorlationPrimary points of regulation are PHOS and PFK

  • Why does G-6-P inhibit glucose phosphorylation?Low level of glycolytic fluxGlycolysis isnt moving very fastMust not need G-6-P

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

  • PHOS regulationPHOS = glycogen phosphorylaseThe enzyme responsible for breakdown of glycogen to glucoseRemoves one glucose at a time by adding Pi (phosphorylating)

  • Insert fig 12.2 from Houston

  • PHOS contdKm of PHOS for glycogen very low (1-2 mM)Means that PHOS has high affinity for glycogenThis means PHOS can function effectively even at low glycogen concentrations

  • More PHOSPrevious exercise can affect glycogenolytic rate relative to glycogen concentrationFor example during afternoon practice following morning practice..If glycogen stores are low, glycogenolysis will be reducedHigher glycogen stores will result in higher relative glycogenolysis

  • Insert fig 1.5

  • Pi and PHOS regulationPhosphorylation of PHOS (pretty redundant eh?) results in conversion of formsb is inactive forma is active formPhosphorylation converts b form to aImplications for activity???

  • At rest 10-20% of PHOS in a formConversion from b to a doesnt necessarily mean increased glycogenolysisFree Pi also needs to be available for elevated glycogenolysis to occur

  • Calcium activates PHOS kinasePhosphorylation of PHOS (again) results from PHOS kinasePHOS kinase activated by elevations in intracellular [Ca2+]

  • Why would you want to tie PHOS to intracellular [Ca 2+]??With E/C coupling Ca2+ released from sarcoplasmic reticulumIntracellular [Ca2+] elevated drastically and rapidlyTherefore glycogenolysis is tied closely to muscular contraction

  • Acidosis hinders PHOS acitivity Conversion of PHOS b to a is depressed under acidic conditionsAfter 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) regulationMost important regulator of PFK activity is ATPATP can bind to PFK at two sites and alter its activityBinds to catalytic site with high affinityCan also bind to allosteric site

  • PFK contdBinding to the allosteric site inhibits activitySo, when [ATP] in the cell is high, PFK will be inhibited no need for glycolysis, plenty of ATPH+ can enhance ATP affinity for allosteric siteProvides feedback inhibition

  • Some other proposed modulatorsInhibitors

    CitratePhosphoglyceratePhophoenolpyruvateMg2+

  • Promoters

    AMP and ADPPiNH4+Fructose 2,6 diphosphate

  • CitrateProbably not a major factor during short, intense exerciseAerobic metabolism does not contribute greatly until later (>30 s)Citrate probably does not accumulate within the 30-60 s time frame

  • PromotersADP and AMP will accumulate rapidly at the onset of anaerobic exerciseBreakdown of PCrH+ may be reduced at the onset of exerciseRemoving the ATP induced inhibition

  • ConclusionPFK regulation is obviously a complicated matterDuring exercise many of the promoters (ADP,AMP, Pi, and NH4+) will accumulateATP will be reduced, but H+ should also riseThere may be unidentified factros which help maintain the awkward balance of promotion and inhibition during intense exercise

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