Purine nucleotides and phosphocreatine

1. Purine nucleotides and phosphocreatine

2. Free energy • ΔG = ΔH – TΔS • G=free energy • H= enthalpy (heat energy) • T= temperature • S=entropy • ΔG • Difference in free energy between the reactants and the products • When direction of Rx is as follows • ATP→ ADP + Pi • ΔG is negative • Because we are losing usuable energy

3. ATP and PCr • Free energy released from the breakdown of CHO and fats • Stored in “high-energy” phosphates • ATP, PCr • Enzymes break down both these compounds to: • ATP: perform cellular work • ATP↔ADP + Pi • ATPase (ATP kinase) • PCr: resynthesize ATP • PCr +ADP↔ATP+Cr • Creatine kinase • Can also use the ADP • ADP + ADP ↔ ATP + AMP • Adenylate kinase

4. ATP • ATP • Adenine, ribose and 3 phosphate groups • Used for almost all energy requiring reactions in the body • Large change in free energy when Pi is cleaved by ATPase • Enough stored to fuel ~2s of maximal effort • Why don’t ATP levels fall? • PCr • Acts as temporal (filling the time until mitochondria comes fully online) buffer of ATP concentrations

5. ATP & PCr • PCr • ~3-4 times as much as ATP • So, now we have ~8s of maximal activity • PCr + ADP ↔ ATP + Cr • This reaction occurs faster than the ATPase reaction • Thus, ATP does not fall • Cr and PCr are more mobile within the cell than ATP • Thus, may also act as a spatial buffer of ATP concentrations

6. ATP and PCr in recovery from work Note how PCr falls and recovers with about the same rate Time constant: ~30-60s PCr recovery is dependent upon Oxygen delivery pH ATP+Cr ↔ ADP + PCr + H+ Note how resynthesis of PCr acidifies the cell

7. Muscle adenylate pool • Energy charge= • Indication of the energy status of the cell • Ability to perform work • Energy charge at rest • Close to 1 • Typically, 0.9-0.95 • Energy charge at complete exhaustion • Close to 0.75

8. Adenylate pool 1 • Changes in the energy charge • Dictate how fast ATP resynthesis occurs • Lower energy charge, faster ATP resynthesis (1) • Accelerates all ATP providing Rx • If energy charge gets low enough (2) • Fatigue • Rate of ATP production and utilization • Same where lines intersect • Note that energy charge is usu above this level • Increased ADP, AMP and Pi stimulate ATP production • Increased ATP inhibits these Rx 2

9. Adenine nucleotide loss 5-nucleotidase • Adenine nucleotide • ATP, ADP, AMP • Adenylate kinase Rx • ATP + AMP ↔ ADP + ADP • Maintains [ATP] • Build up of AMP limits this Rx • Convert AMP • IMP or adenosine • IMP and Inosine • Can be re-converted to AMP or leaves the body as uric acid • Mostly seen in type II muscle fibers • Allows AK Rx to occur, maintaining high ATP concentrations

10. Purine nucleotide cycle • Occurs in cytoplasm • AMP deaminase • AMP to IMP • Ammonia formation • Activated by decrease in energy charge • Adenylosuccinate synthetase • IMP to adenylosuccinate • Loss of Pi • Adenylosuccinate lyase • Adenylosuccinate to AMP • Fumarate produced • Purpose of cycle • Maintenance of cellular energy charge • Recycling of adenylate pool

11. Reamination in the PNC • Adenylosuccinate synthetase and lyase • Reamination occurs in recovery • Fumarate is produced • Helps maintain the Kreb’s cycle (6th step) • Ammonia is produced • Excreted in urine • Deamination: • Helps maintain energy charge during contractions • Reamination: • Replenished muscle adenylate pool