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

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Purine nucleotides and phosphocreatine

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

Page 1: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

Purine nucleotides and phosphocreatine

Page 2: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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

Page 3: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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

Page 4: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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

Page 5: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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

Page 6: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

•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

ATP and PCr in recovery from work

Page 7: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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

Page 8: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

Adenylate pool• 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

1

2

Page 9: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

Adenine nucleotide loss• 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

5-nucleotidase

Page 10: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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

Page 11: Purine nucleotides and phosphocreatine. Free energy ΔG = ΔH – TΔS –G=free energy –H= enthalpy (heat energy) –T= temperature –S=entropy ΔG –Difference.

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