Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Chapter 3 Thermodynamics of Biological Systems to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Outline Basic Thermodynamic Concepts Physical Significance of Thermodynamic Properties pH and the Standard State The Effect of Concentration Coupled Processes High-Energy Biomolecules

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Basic Concepts The system: the portion of the universe with which we are concerned The surroundings: everything else Isolated system cannot exchange matter or energy Closed system can exchange energy Open system can exchange either or both

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company The First Law The total energy of an isolated system is conserved. E (or U) is the internal energy - a function that keeps track of heat transfer and work expenditure in the system E is heat exchanged at constant volume E is independent of path E 2 - E 1 =  E = q + w q is heat absorbed BY the system w is work done ON the system

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Enthalpy A better function for constant pressure H = E + PV If P is constant,  H = q  H is the heat absorbed at constant P Volume is approx. constant for biochemical reactions (in solution) So  H is approx. same as  E

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company The Second Law Systems tend to proceed from ordered to disordered states The entropy change for (system + surroundings) is unchanged in reversible processes and positive for irreversible processes All processes proceed toward equilibrium - i.e., minimum potential energy

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Entropy A measure of disorder An ordered state is low entropy A disordered state is high entropy dS reversible = dq/T

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company The Third Law The entropy of any crystalline, perfectly ordered substance must approach zero as the temperature approaches 0 K At T = 0 K, entropy is exactly zero For a constant pressure process: C p = dH/dT

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Free Energy Hypothetical quantity - allows chemists to asses whether reactions will occur G = H - TS For any process at constant P and T:  G =  H - T  S If  G = 0, reaction is at equilibrium If  G < 0, reaction proceeds as written

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company  G versus  G o ’ How can we calculate the free energy change for rxns not at standard state? Consider a reaction: A + B  C + D Then:  G =  G o ’ + RT ln ([C][D]/[A][B])

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Energy Transfer A Crucial Biological Need Energy acquired from sunlight or food must be used to drive endergonic (energy-requiring) processes in the organism Two classes of biomolecules do this: –Reduced coenzymes (NADH, FADH 2 ) –High-energy phosphate compounds - free energy of hydrolysis larger than -25 kJ/mol)

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company High-Energy Biomolecules Study Table 3.3! Note what's high - PEP and 1,3-BPG Note what's low - sugar phosphates, etc. Note what's in between - ATP! Note difference (Figure 3.8) between overall free energy change - noted in Table and the energy of activation for phosphoryl-group transfer!

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company ATP An Intermediate Energy Shuttle Device PEP and 1,3-BPG are created in the course of glucose breakdown Their energy (and phosphates) are transferred to ADP to form ATP But ATP is only a transient energy carrier - it quickly passes its energy to a host of energy-requiring processes

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Phosphoric Acid Anhydrides Why ATP does what it does! ADP and ATP are examples of phosphoric acid anhydrides Note the similarity to acyl anhydrides Large negative free energy change on hydrolysis is due to: –electrostatic repulsion –stabilization of products by ionization and resonance –entropy factors

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Phosphoric-Carboxylic Anhydrides These mixed anhydrides - also called acyl phosphates - are very energy-rich Acetyl-phosphate:  G°´ = kJ/mol 1,3-BPG:  G°´ = kJ/mol Bond strain, electrostatics, and resonance are responsible

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Enol Phosphates Phosphoenolpyruvate (PEP) has the largest free energy of hydrolysis of any biomolecule Formed by dehydration of 2-phospho- glycerate Hydrolysis of PEP yields the enol form of pyruvate - and tautomerization to the keto form is very favorable

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Ionization States of ATP ATP has five dissociable protons pK a values range from 0-1 to 6.95 Free energy of hydrolysis of ATP is relatively constant from pH 1 to 6, but rises steeply at high pH Since most biological reactions occur near pH 7, this variation is usually of little consequence

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company The Effect of Concentration Free energy changes are concentration dependent We will use the value of kJ/mol for the standard free energy of hydrolysis of ATP But at non-standard-state conditions (in a cell, for example), the  G is different! Equation 3.12 is crucial - be sure you can use it properly In typical cells, the free energy change for ATP hydrolysis is typically -50 kJ/mol

Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company