10/22/2012

Reginald H. Garrett Charles M. Grisham

www.cengage.com/chemistry/garrett

Chapter 3 Thermodynamics of Biological Systems

Reginald Garrett & Charles Grisham University of Virginia

Chapter 3
The sun is the source of energy for virtually all life. We even harvest its energy in the form of electricity generated by windmills. Wind is the movement of air that has been heated by the sun.

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Essential Question
What are the laws and principles of thermodynamics that allow us to describe the flows and interchanges of heat, energy, and matter in biochemical systems? BSIC CONCEPT OF Temperature Energy System

3.1 What Are the Basic Concepts of Thermodynamics?

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

Figure 3.1 The characteristics of isolated, closed, and open systems. Isolated systems exchange neither matter nor energy with their surroundings. Closed systems may exchange energy, but not matter, with their surroundings. Open systems may exchange either matter or energy with the surroundings.

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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 E2 - E1 = E = q + w q is heat absorbed BY the system w is work done ON the system Thus both q and w are positive when energy flows into a system State Function- The E is dependant on the system w = -PV

Enthalpy
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 approximately constant for biochemical reactions (in solution) So H is approximately the same as E for biochemical reactions CH4 + O2 CH2O + H2O (H = -319.7 kJ.mol-1) Exothermic CH2O + H2O CH4 + O2 (H = +319.7 kJ.mol-1) Endothermic

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3.1 What Are the Basic Concepts of Thermodynamics?

Figure 3.2 The enthalpy change for a reaction can be determined from the slope of a plot of R ln Keq versus 1/T.

3.1 What Are the Basic Concepts of Thermodynamics?

Positive values of H would be expected for the breaking of hydrogen bonds as well as for the exposure of hydrophobic groups from the interior of a native, folded protein during the unfolding process. Such events raise the energy of the solution.

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The Second Law Systems Tend Toward Disorder and Randomness

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 S= k ln W; S = k ln Wfinal-k ln Winitial ( W= microstate) k is Boltzmanns constant (1.38x10-23J/K) A measure of disorder An ordered state is low entropy A disordered state is high entropy dSreversible = dq/T , dq= heat transferred, T = Temperature

What is Life?, asked Erwin Schrdinger, in 1944.

A disorganized array of letters possesses no information content and is a high-entropy state, compared to the systematic array of letters in a sentence. Erwin Schrdingers term negentropy describes the negative entropy changes that confer organization and information content to living organisms. Schrdinger pointed out that organisms must acquire negentropy to sustain life.

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Energy dispersion
Entropy can be defined as S = k ln W And S = k ln Wfinal k ln Winitial Where Wfinal and Winitial are the final and initial number of microstates of a system, and k is Boltzmanns constant. Viewed in this way, entropy represents energy dispersion the dispersion of energy among a large number of molecular motions relatable to quantized states (microstates). The definition of entropy above is engraved on the tombstone of Ludwig Boltzmann in Vienna, Austria If microstate is one ( i.e. no degree of freedoms, S= 0) dSreversible = dq/T

The Third Law Why Is Absolute Zero So Important?

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 (heat capacity Cp) : Cp = dH/dT

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Free Energy
Hypothetical quantity - allows chemists to asses whether reactions will occur G = H TS (H, enthalpy or total energy, S= entropy)

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 (spontaneous backward reaction) (Endergonic) G >0 , spontaneous reaction (Exergonic)

G and Go - The Effect of Concentration on G

How can we calculate the free energy change for reactions not at standard state? Consider a reaction: A + B C + D Then: [C][D] G = G o + RT ln [ A][B] At equilibrium G = 0 and [C][D]/[A][B]= Keq G=-RT ln Keq G=--2.3 RT log10 Keq Keq= 10-G/2.3RT Thus concentrations at other than 1 M will change the value of G This is Equation 3.13. It is used frequently throughout this text.

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G Can Be Temperature Dependent

Figure 3.3 The dependence of G on temperature for the denaturation of chymotrypsinogen.

S Can Be Temperature Dependent

Figure 3.4 The dependence of S on temperature for the denaturation of chymotrypsinogen.

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3.3 What is the Effect of pH on Standard State Free Energies?

A standard state of 1 M for H+ is not typical for biochemical reactions. It makes more sense to adopt a modified standard state i.e., 1 M for all constituents except protons, for which the standard state is pH 7. This standard state is denoted with a superscript For reactions in which H+ is produced: G= G + RT ln [H+] And for reactions in which H+ is consumed: G = G - RT ln [H+]

3.4 What Can Thermodynamic Parameters Tell Us About Biochemical Events?

A single thermodynamic parameter is not very useful Comparison of several thermodynamic parameters can provide meaningful insights about a process Heat capacity values can be useful A positive heat capacity change for a process indicates that molecules have acquired new ways to move (and thus to store heat energy) A negative heat capacity change means that the process has resulted in less freedom of motion for the molecules involved

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3.4 What Can Thermodynamic Parameters Tell Us About Biochemical Events?

Figure 3.5 Unfolding of a soluble protein exposes significant numbers of nonpolar groups to water, forcing order on the solvent and resulting in a negative entropy change.

3.4 What Can Thermodynamic Parameters Tell Us About Biochemical Events?

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3.5 What are the Characteristics of High-Energy Biomolecules?

Energy Transfer - A Biological Necessity 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, FADH2) High-energy phosphate compounds with free energy of hydrolysis more negative than -25 kJ/mol

High-Energy Biomolecules
Table 3.3 is important 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 3.6) between overall free energy change - noted in Table 3.3 - and the energy of activation for phosphoryl-group transfer

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3.5 What are the Characteristics of High-Energy Biomolecules?

3.5 What Are the Characteristics of High-Energy Biomolecules?

Figure 3.6 The activation energies for phosphoryl group transfer reactions are substantially larger than the free energy of hydrolysis of ATP.

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Group Transfer Potentials Quantify the Reactivity of Functional Groups

Group transfer is analogous to ionization potential and reduction potential. All are specific instances of free energy changes.

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

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ATP Contains Two Pyrophosphate Linkages

Figure 3.7 ATP contains two pyrophosphate linkages. The hydrolysis of phosphoric acid anhydrides is highly favorable.

Phosphoric Acid Anhydrides

How 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

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Hydrolysis of Phosphoric Anhydrides is Highly Favorable

Figure 3.8 Electrostatic repulsion and resonance in acetic anhydride

3.5 What Are the Characteristics of High-Energy Biomolecules?

Figure 3.9 Hydrolysis of ATP to ADP (and hydrolysis of ADP to AMP) relieves electrostatic repulsion.

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Phosphoric-Carboxylic Anhydrides
These mixed anhydrides - also called acyl phosphates - are very energy-rich Acetyl-phosphate: G = 43.3 kJ/mol 1,3-BPG: G = 49.6 kJ/mol Bond strain, electrostatics, and resonance are responsible

Acetyl Phosphate and 1,3-Bisphosphoglycerate Are PhosphoricCarboxylic Anhydrides

Figure 3.10 The hydrolysis reactions of acetyl phosphate and 1,3bisphosphoglycerate.

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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

PEP Hydrolysis Yields -62.2 kJ/mol

Figure 3.11 PEP is produced by the enolase reaction and in turn drives the phosphorylation of ADP to form ATP in the pyruvate kinase reaction.

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Enol Phosphates are Potent Phosphorylating Agents

Figure 3.12 Hydrolysis and subsequent tautomerization account for the very large G of PEP.

Ionization States of ATP

ATP has four dissociable protons pKa 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

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3.6 What Are the Complex Equilibria Involved in ATP Hydrolysis?

The Free Energy of Hydrolysis for ATP is pHDependent

Figure 3.14 The pH dependence of the free energy of hydrolysis of ATP. Because pH varies only slightly in biological environments, the effect on G is usually small.

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Metal Ions Affect the Free Energy of Hydrolysis of ATP

Figure 3.15 The free energy of hydrolysis of ATP as a function of total Mg2+ ion concentration at 38C and pH 7.0.

Metal Ions Affect the Free Energy of Hydrolysis of ATP

Figure 3.16 Number of Mg2+ ions bound per ATP as a function of pH and [Mg2+ ].

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Concentration Affects the Free Energy of Hydrolysis of ATP

Figure 3.17 The free energy of hydrolysis of ATP as a function of concentration at 38C, pH 7.0.

The Effect of Concentration

Recall that free energy changes are concentration- dependent So the free energy available from ATP hydrolysis depends on concentration We will use the value of 30.5 kJ/mol for the standard free energy of hydrolysis of ATP At non-standard-state conditions (in a cell, for example), the G is different Equation 3.13 allows the calculation of G - be sure you can use it properly In typical cells, the free energy change for ATP hydrolysis is typically 50 kJ/mol

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3.7 Why Are Coupled Processes Important to Living Things?

Many reactions of cells and organisms run against their thermodynamic potential that is, in the direction of positive G Examples synthesis of ATP, creation of ion gradients These processes are driven in the thermodynamically unfavorable direction via coupling with highly favorable processes

3.7 Why Are Coupled Processes Important to Living Things?

Figure 3.18 The pyruvate kinase reaction. Hydrolysis of PEP is very favorable, and it is used to drive phosphorylation of ADP to form ATP, a process that is energetically unfavorable.

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3.8 What is the Daily Human Requirement for ATP?

The average adult human consumes approximately 11,700 kJ of food energy per day Assuming thermodynamic efficiency of 50%, about 5860 kJ of this energy ends up in form of ATP Assuming 50 kJ of energy required to synthesize one mole of ATP, the body must cycle through 5860/50 or 117 moles of ATP per day This is equivalent to 65 kg of ATP per day The typical adult human body contains 50 g of ATP/ADP Thus each ATP molecule must be recycled nearly 1300 times per day

ATP Changes Keq by 108

Consider a process: A B Compare this to A + ATP B + ADP + Pi Assuming typical cellular concentrations of ATP, ADP and Pi, and using the cellular free energy change for ATP hydrolysis, it can be shown that coupling ATP hydrolysis to the reaction of A B changes the equilibrium ratio of B/A by more than 200 million-fold

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ATP Changes Keq by 108

3.9 What Are Reduction Potentials?

How Are Reduction Potentials Used to Calculate Free Energy Changes for Oxidation-Reduction Reactions? High o' indicates a strong tendency to be reduced Crucial equation: Go' = n o' o' = o'(acceptor) - o'(donor) Electrons are donated by the half reaction with the more negative reduction potential and are accepted by the reaction with the more positive reduction potential: o ' positive, Go' negative If a given reaction is written so the reverse is true, then the o' will be a negative number and Go' will be positive

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