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The Use of the Energy in ATP for Muscle Contractions

The Use of the Energy in ATP for Muscle Contractions. Nitya Anand Melissa Donaldson Leigh McDonald Chris Smyre. Adenine. What is ATP?. ATP: Adenosine Tri-phosphate. Ribose. 3 phosphate groups. Muscle contractions require the use of actin filaments and myosin molecular motors.

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The Use of the Energy in ATP for Muscle Contractions

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  1. The Use of the Energy in ATP for Muscle Contractions Nitya Anand Melissa Donaldson Leigh McDonald Chris Smyre

  2. Adenine What is ATP? ATP: Adenosine Tri-phosphate Ribose 3 phosphate groups

  3. Muscle contractions require the use of actin filaments and myosin molecular motors. • The movable myosin heads pull along the actin, causing muscles to shorten. • This process is driven by the release of energy from an ATP (adenosine triphosphate) molecule. • As such, ATP is the major energy currency in the human body. How Do Muscles Contract?

  4. “Myosin II’ Actomyosin Mechanism • A: ATP binds to myosin heads, releasing it from binding the actin. • B: ATP is hydrolyzed to ADP and Pi. The myosin head moves back due to the energy release, but does not release the ADP/Pi. • C: Pi leaves the myosin head, so it can bind to the actin. • D: The myosin pulls the actin filament forward as it releases ADP in what is called the “power stroke”. (Geeves, 1999)

  5. The Importance of ATP • Energy is released when ATP is hydrolyzed to ADP and Pi, causing a conformational shift. • This energy goes into the myosin head, which allows it to pull back in order to drive the “power stroke” seen in part D. • http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter10/animation__breakdown_of_atp_and_cross-bridge_movement_during_muscle_contraction.html • If there is no ATP available, there will be no energy to drive the head backwards. Additionally, without ATP, the myosin cannot release the actin filament. This is the primary cause of rigor mortis.

  6. Mechanism of ATP Hydrolysis ATP + H2O ↔ ADP + Pi

  7. Thermodynamics of ATP Hydrolysis Theoretically, based on bond energies: -A°=ΔG°=-30.5 kJ/mol at 25 °C, 1 atm To find ΔG under normal cellular conditions: Start with equation for affinity: Thus for the reaction ATP + H2O → ADP + Pi +H+, Cells usually maintain a high ratio of ATP to ADP, resulting in ΔG~-50 kJ/mol

  8. Reaction Coupling Reactions with positive ΔG can be coupled with reactions with negative ΔG Allows the cell to undergo reactions that are not thermodynamically favorable Example: formation of glutamine from glutamic acid Glutamic acid + NH3 → glutamine ΔG=+14.2 kJ/mol In the presence of ATP: Glutamic acid + ATP → glutamyl phosphate + ADP Glutamyl phosphate + NH3 → glutamine + Pi Total ΔGrxn= -16.3 kJ/mol Application of this during muscle contraction: energy from ATP hydrolysis induces conformation change in myosin

  9. Binding of ATP and Conformational Change in Myosin Pre-powerstroke EA Relative free energy (ΔG) Myosin head can assume two different structural conformations EA for the change from low energy to high energy conformation is provided by ATP hydrolysis Rigor state Reaction progress/distance

  10. Entropy • Second Law of Thermodynamics • Entropy is always increasing in the universe • 2 Components in changes of Entropy (dS= deS+diS) • deS: Entropy change due to exchange of matter & energy Can be negative or positive • diS: Entropy change due to irreversible processes deS Will be > 0 • Spontaneous Reactions are Irreversible • Entropy production Similar to a Carnot cycle diS>0 • in ATP hydrolysis process

  11. Irreversibility of ATP cleavage • 4 forms of energy: • Gibb’s Energy • Helmoltz’s Energy • Enthalpy Energy • Total Energy • Energy is always being minimized • Gibb’s Energy is the easiest to measure T & P held constant • We know that ATPADP drop in Gibb’s energy

  12. Conclusion • ATP hydrolysis is important in biological processes such as the actomyosin cross-bridging that controls muscle contractions. • To drive contractions, ATP is used in a coupled reaction that results in an exothermic (negative) Gibbs Free Energy for the reaction. • Entropy change in the process is analogous to the change in entropy in a Carnot cycle which explains the heat generated by muscle contractions.

  13. References “Animation: Breakdown of ATP and Cross-Bridge Movement During Muscle Contraction.” McGraw-Hill Higher Education. The McGraw-Hill Companies. <http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter10/animation__breakdown_of_atp_and_cross-bridge_movement_during_muscle_contraction.html> Burghardt, T.P., Yan Hu, J., Ajtai, K. (2007). Myosin dynamics on the millisecond time scale. Biophysical Chemistry, 131 (1-3), 15-28. Geeves, M.A. & Holmes, K.C. 1999. Structural mechanism of muscle contraction. ANNUAL REVIEW OF BIOCHEMISTRY 68: 687-728. Karp, G.C. (2008). Cell and Molecular Biology: Concepts and Experiments. Atlantic Highlands: John Wiley and Sons, Inc. Kondepudi, D. (2008). Introduction to Modern Thermodynamics. West Sussex: John Wiley and Sons Ltd. “Myosin II.” College of Medicine: School of Biomedical Sciences. The University of Edinburgh. 30 Nov. 2008 <http://www.bms.ed.ac.uk/research/others/smaciver/Myosin%20II.htm>.

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