Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H=...

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Transcript of Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H=...

  • Purine nucleotides and phosphocreatine

  • Free energyG = H TSG=free energyH= enthalpy (heat energy)T= temperatureS=entropyGDifference in free energy between the reactants and the productsWhen direction of Rx is as followsATP ADP + PiG is negativeBecause we are losing usuable energy

  • ATP and PCrFree energy released from the breakdown of CHO and fatsStored in high-energy phosphatesATP, PCrEnzymes break down both these compounds to:ATP: perform cellular workATPADP + PiATPase (ATP kinase)PCr: resynthesize ATPPCr +ADPATP+CrCreatine kinase Can also use the ADPADP + ADP ATP + AMPAdenylate kinase

  • ATPATPAdenine, ribose and 3 phosphate groupsUsed for almost all energy requiring reactions in the bodyLarge change in free energy when Pi is cleaved by ATPaseEnough stored to fuel ~2s of maximal effortWhy dont ATP levels fall?PCrActs as temporal (filling the time until mitochondria comes fully online) buffer of ATP concentrations

  • ATP & PCrPCr~3-4 times as much as ATPSo, now we have ~8s of maximal activityPCr + ADP ATP + CrThis reaction occurs faster than the ATPase reactionThus, ATP does not fallCr and PCr are more mobile within the cell than ATPThus, may also act as a spatial buffer of ATP concentrations

  • Note how PCr falls and recovers with about the same rateTime constant: ~30-60sPCr recovery is dependent uponOxygen deliverypHATP+Cr ADP + PCr + H+ Note how resynthesis of PCr acidifies the cellATP and PCr in recovery from work

  • Muscle adenylate poolEnergy charge=Indication of the energy status of the cellAbility to perform workEnergy charge at restClose to 1Typically, 0.9-0.95Energy charge at complete exhaustionClose to 0.75

  • Adenylate poolChanges in the energy chargeDictate how fast ATP resynthesis occursLower energy charge, faster ATP resynthesis (1)Accelerates all ATP providing RxIf energy charge gets low enough (2)FatigueRate of ATP production and utilizationSame where lines intersectNote that energy charge is usu above this levelIncreased ADP, AMP and Pi stimulate ATP productionIncreased ATP inhibits these Rx12

  • Adenine nucleotide lossAdenine nucleotideATP, ADP, AMPAdenylate kinase RxATP + AMP ADP + ADPMaintains [ATP]Build up of AMP limits this RxConvert AMPIMP or adenosineIMP and InosineCan be re-converted to AMP or leaves the body as uric acidMostly seen in type II muscle fibersAllows AK Rx to occur, maintaining high ATP concentrations

    5-nucleotidase

  • Purine nucleotide cycleOccurs in cytoplasmAMP deaminaseAMP to IMPAmmonia formationActivated by decrease in energy chargeAdenylosuccinate synthetaseIMP to adenylosuccinateLoss of PiAdenylosuccinate lyaseAdenylosuccinate to AMPFumarate produced Purpose of cycleMaintenance of cellular energy chargeRecycling of adenylate pool

  • Reamination in the PNCAdenylosuccinate synthetase and lyaseReamination occurs in recoveryFumarate is produced Helps maintain the Krebs cycle (6th step)Ammonia is producedExcreted in urineDeamination: Helps maintain energy charge during contractionsReamination:Replenished muscle adenylate pool

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