Thermodynamics enzyme catalysis reactions

Thus, room-temperature ionic liquids have the potential to provide environmentally friendly solvents for the chemical and pharmaceutical industries. The ionic liquid environment is very different from normal polar and nonpolar organic solvents both the thermodynamics and the kinetics of chemical reactions are different, and so the outcome of a reaction may also be different. Organic reactions that have been successfully studied in ionic liquids include Friedel-Crafts, Diels-Alder,Heck catalysis, chlorination, enzyme catalysis,polymeriz-... 

Miller and Wolfenden6 compared the rates of decarboxylation of the substrate of orotidine-5 -monophosphate decarboxylase (OMPDC) in quantitative detail, on and off the enzyme. They showed that the apparent unimolecular rate constant of decarboxylation of the substrate when bound to the enzyme is about 1015 times greater than the decarboxylation process in the absence of the enzyme. Further studies confirm that the enzyme-promoted reaction does not involve additional intermediates or covalent alterations of the substrate. The reaction consists of carbon dioxide being formed and the resulting carbanion becoming protonated. Since thermodynamic barriers are not altered by catalysis, the energy of the carbanion must be a component that reflects the energy of the environment in which it is created, one in which the carbanion that is formed is selectively stabilized. 

Important milestones in the rationalization of enzyme catalysis were the lock-and-key concept (Fischer, 1894), Pauling s postulate (1944) and induced fit (Koshland, 1958). Pauling s postulate claims that enzymes derive their catalytic power from transition-state stabilization the postulate can be derived from transition state theory and the idea of a thermodynamic cycle. The Kurz equation, kaJkunat Ks/Kt, is regarded as the mathematical form of Pauling s postulate and states that transition states in the case of successful catalysis must bind much more tightly to the enzyme than ground states. Consequences of the Kurz equation include the concepts of effective concentration for intramolecular reactions, coopera-tivity of numerous interactions between enzyme side chains and substrate molecules, and diffusional control as the upper bound for an enzymatic rate. 

There has been a resurgence of interest in proton-coupled redox reactions because of their importance in catalysis, molecular electronics and biological systems. For example, thin films of materials that undergo coupled electron and proton transfer reactions are attractive model systems for developing catalysts that function by hydrogen atom and hydride transfer mechanisms [4]. In the field of molecular electronics, protonation provides the possibility that electrons may be trapped in a particular redox site, thus giving rise to molecular switches [5]. In biological systems, the kinetics and thermodynamics of redox reactions are often controlled by enzyme-mediated acid-base reactions. 

It is generally held that an aqueous environment is desirable, although not a prerequisite, for the optimal activity of enzymes. It is assumed that in most cases, placing an enzyme in an organic medium will cause deleterious effects to the tertiary structure of the protein. However, if this was not the case, there would be potential advantages for enzyme catalysis in an organic medium. It would clearly facilitate conversion of water-insoluble substrates and aid in product recovery. The thermodynamic equilibria of certain reactions are unfavorable in aqueous systems. Enzyme stereoselectivity has been shown to improve in some nonaqueous enzyme transformations (67,68). 

In considering thermodynamic parameters, e.g., heat and work, we do not need to know the exact chemical pathway taken by the reactants in conversion to products. Using thermodynamics, we can obtain information about reactions that cannot be studied directly in living systems. Thermodynamics predicts, on the basis of the known energy levels of reactants and products, whether a reaction can be expected to occur spontaneously or how much energy must be supplied to drive the reaction in one direction or another. Such information is crucial in establishing reaction routes in metabolic pathways. Thermodynamics explains how equilibrium constants are related to changes in temperature. Thermodynamics also explains the basis for enzyme catalysis. 

Enzymic catalysis of a rearrangement reaction has special mechanistic fascination and, for vitamin B12, a methyl group at C-11 of 66 shifts to C-12 of 60, Scheme 25. This step clears the blockage to movement of the double bonds so tautomerisation can now occur, with thermodynamic gain, to form the extended conjugated system of hydrogenobyrinic acid 60. The enzyme responsible for... 

Studies on proton transfer to and from carbon in model reactions have shown that the activation barrier to most enzyme-catalyzed reactions is composed mainly of the thermodynamic barrier to proton transfer (Fig. 1.1), so that in most cases this barrier for proton transfer at the enzyme active site will need to be reduced in order to observe efficient catalysis. A smaller part of the activation barrier to deprotonation of a-carbonyl carbon is due to the intrinsic difficulty of this reaction to form a resonance stabilized enolate. There is evidence that part of the intrinsic barrier to proton transfer at a-carbonyl carbon reflects the intrinsic instability of negative charge at the transition state of mixed sp -sp -hybridization at carbon [79]. Small buffer and metal ion catalysts do not cause a large reduction in this intrinsic reaction barrier. 

Enzymes are protein and/or RNA molecules that catalyze chemical reactions. Chemical reactions in biological systems are almost always catalyzed, otherwise they would occur too slowly. The catalysts that are used are proteins (except for a few instances of catalysis by RNA) although other molecules (prosthetic groups, coenzymes) may also be required. The main functional characteristics of enzymes compared with chemical catalysts are their high efficiency, their specificity, and their capacity for regulation. Enzyme-catalyzed reactions can lead to the transformation of energy from one state to another. Enzyme-catalyzed reactions conform to the same laws of thermodynamics as chemical reactions and engines. 

Nuclear relaxation studies of substrates and inhibitors have resulted in the detection of 10 enzyme-Mur-substrate and 4 enzyme-Mn-inhibitor bridge complexes possessing kinetic and thermodynamic properties consistent with their participation in enzyme catalysis. Three cases of a activation, by divalent cations, of enzyme-catalyzed enolization reactions (pyruvate carboxylase, yeast aldolase, v-xylose isomerase), and one case of 8 activation of an enzyme-catalyzed elimination reaction (histidine deaminase) have thereby been established, Thus, in each proven case, the enzyme-bound Mn coordinates an electronegative atom (Z) of the substrate, which is attached to a carbon atom one or two bonds away from the carbon atom which is to be deprotonated ... 

Finally, we end the chapter with a discussion of nature s catalysts enzymes. In fact, we allude to enzymes throughout the chapter. The general manner in which enzymes catalyze reactions is still a matter of debate, and so we present several theories. Our examination of enzymes is in preparation for a few specific enzymatic examples given in Chapters 10 and 11 as highlights for organic reaction mechanisms. Enzymes also provide an excellent setting in which to discuss Michaelis-Menton kinetics, the most common kinetic scenario used for catalysis. We also return to our analysis of the power of changing the thermodynamic reference state to examine reactivity, and show the manner in which an enzyme becomes "perfect". 

The first notion on the deviation of elementary catalytic acts of enzyme reaction, from that prescribed by classical thermodynamic and kinetic approaches, was, probably, formulated in 1971 [19]. It had been shown that the application of basic postulates of activated state theory to the majority of enzyme processes can lead to physically meaningless values of the activation parameters (energy and entropy of activation). It was emphasized that enzyme functioning is more similar to the work of a mechanical construction than to the catalytic homogeneous chemical reaction. The selfconsistent phenomenological relaxation theory of enzyme catalysis was proposed in 1972 [20, 21]. 

---