Energetics of Biochemical Reactions

To get a deeper insight into the metabolic and energetic processes, knowledge of general principles of chemical energetics appears to be of help. 

However, from the practical standpoint it appears expedient to use the so-called free energy which, in contrast to entropy, is amenable to measurement in the course of a reaction. The free energy defines a portion of the total energy of a system that can be converted to work at pressure and temperature kept constant. The free energy is 

The energetic state of any system, including that of a cell and an organism, can be defined in terms of this very important equation. The free energy is expressed in kilojoules per mole of substance, kJ/ mol. 

The free energy of chemical reactions may be estimated both under the standard conditions and under real, or physiological, conditions. The standard free energy, AG°, of a biochemical reaction is defined as a free energy change under the standard conditions, i.e. at the concentration of reactants 1 mol/litre, temperature 25 °C 298 X), and pH 7. 

If water is involved either as a starting compound or as a reaction product, its concentration is taken equal to 1.0 mol/litre, although the true concentration of water in dilute aqueous solutions is close to 55 mol/litre. 

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The free-energy change, A G, will be used throughout this book to describe the energetics of biochemical reactions. 

Detailed information on the mechanism of biochemical reactions may be of crucial importance in designing new molecules having a pharmacological activity. For example, the detailed mechanism of protein hydrolysis by thermolysin has been studied at the QM/MM semiempirical level [25]. The various steps of the reaction and their transition states have been characterized. Fig. 3 (see color plate) shows the structure of the transition state of the rate-determining step. The important consequence of this approach is the fact that it is possible to evaluate the influence of the whole macro-molecular surroundings on the energetics of the process. It then becomes possible, for instance, to predict the influence of a mutation on the reaction kinetics. 

I. M. Klotz, Some Principles of Energetics in Biochemical Reactions, Academic Press, New... 

Higgins L, Korzekwa KR, Rao S, et al. An assessment of the reaction energetics for cytochrome P450-mediated reactions. Arch Biochem Biophys 2001 385(l) 220-230. 

From an energetic viewpoint, these reactions fuel a good number of biological functions which are responsible for biochemical reactions crucial to life . In common chemical processes, these reactions require the use of heterogeneous catalytic systems and drastic reaction conditions (pressures of 100 atm and temperatures around 400°C), whereas, at a cellular level, they proceed smoothly under ambient conditions (room temperature and 1 atm pressure). 

Peters. K.S. and G.J. Snyder, Time-Resolved Photoacoustic Calorimetry Probing the Energetics and Dynamics of Fast Chemical and Biochemical Reactions, Science. 1053 (August 26, 1988). 

The equations and calculations described in this chapter are very useful, but so far we have not discussed thermodynamic properties other than equilibrium constants. The other properties introduced in the next three chapters provide a better understanding of the energetics and equilibria of reactions. We will consider the basic structure of thermodynamics in Chapter 2 and then to apply these ideas to chemical reactions in Chapter 3 and biochemical reactions in Chapter 4. 

In principle, feeble interactions should be carefully considered in drawing the pathway of a reaction, because they affect the energetic level of reactants and transition states. Consequently, these non-covalent interactions are important for recognizing the actual nature of the reagents (energy levels and geometry, aggregation with solvent or other solutes), in order to explain chemical and biochemical behaviours. 

NADH (nicotinamide adenine dinucleotide) is a biochemical source of hydride. In the following example NADH reduces acetaldehyde to ethanol via minor pathway H t., hydride transfer to a cationic center. A Zn ion acts as a Lewis acid to polarize the acetaldehyde carbonyl (similar to protonating the carbonyl). The Lewis acid makes the carbonyl a better electron sink by increasing the partial positive charge on carbon. In fact, the electrophilic catalysis by 2+ and 3+ metal ions can accelerate additions to carbonyls by over a million times. The formation of the aromatic pyridinium ring in the NAD" product helps balance the energetics of this easily reversible reaction. 

The biochemical applications involve the electronic nature of the components of DNA and proteins, especially the charge distributions, electron affinities, and gas phase acidities of purines and pyrimidines and amino acids. The role of electron reactions in diverse areas such as cancer, electron conduction, and sequence recognition all depend on fundamental energetic properties such as electron affinities and solution energies. We explain nonadiabatic experimental data from radiation chemistry by excited anionic states of biological molecules [24],... 

What forces cause the two strands of DNA to bind to each other To analyze this binding reaction, we must consider several factors the types of interactions and bonds in biochemical systems and the energetic favorabil-ity of the reaction. We also must consider the influence of the solution conditions—in particular, the consequences of acid—base reactions. 

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