Enzymic energetics

This enzyme [EC 5.1.1.4] catalyzes the interconversion of L-proline and D-proline. See Enzyme Energetics (The... 

Free energy diagrams for enzymes REACTION COORDINATE DIAGRAM ENZYME ENERGETICS POTENTIAL-ENERGY SURFACES TRANSITION-STATE THEORY ARRHENIUS EQUATION VAN T HOFF RELATIONSHIP... 

ENZYME ENERGETICS ISQTQPIC PERTURBATION KINETIC PARAMETERS KINETIC RESOLUTION KING-ALTMAN METHOD... 

TRIOSE-PHOSPHATE ISOMERASE AFFINITY LABELING HALDANE RELATION ENZYME ENERGETICS (The Case of Proline Racemase)... 

Dinitrogen has a dissociation energy of 941 kj/mol (225 kcal/mol) and an ionisation potential of 15.6 eV. Both values indicate that it is difficult to either cleave or oxidize N2. For reduction, electrons must be added to the lowest unoccupied molecular orbital of N2 at —7 eV. This occurs only in the presence of highly electropositive metals such as lithium. However, lithium also reacts with water. Thus, such highly energetic interactions ate unlikely to occur in the aqueous environment of the natural enzymic system. Even so, highly reducing systems have achieved some success in N2 reduction even in aqueous solvents. 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

The subtilisin mutants described here illustrate the power of protein engineering as a tool to allow us to identify the specific roles of side chains in the catalytic mechanisms of enzymes. In Chapter 17 we shall discuss the utility of protein engineering in other contexts, such as design of novel proteins and the elucidation of the energetics of ligand binding to proteins. 

Knowles, J., and Albery, W., 1977. Perfection in enzyme catalysis The energetics of triose phosphate isomerase. Accounts of Chemical Research 10 105-111. 

Reactions involve several enzymes, which have to follow in sequence for lactic acid and alcohol fermentation. This is known as the glucose catabolism pathway, with emphasis on energetic and energy carrier molecules such as ATP, ADP, NAD+ and NADH. In this pathway the six-carbon substrate yields two three-carbon intermediates, each of which passes through a sequence of reactions to the stable end product of pyruvic acid. 

After the somewhat tedious parametrization procedure presented above you are basically an expert in the basic chemistry of the reaction and the questions about the enzyme effect are formally straightforward. Now we only want to know how the enzyme changes the energetics of the solution EVB surface. Within the PDLD approximation we only need to evaluate the change in electrostatic energy associated with moving the different resonance structures from water to the protein-active site. 

With the valence bond structures of the exercise, we can try to estimate the effect of the enzyme just in terms of the change in the activation-free energy, correlating A A g with the change in the electrostatic energy of if/2 and i/r3 upon transfer from water to the enzyme-active site. To do this we must first analyze the energetics of the reaction in solution and this is the subject of the next exercise. 

Once the energetics of the reference reaction are estimated we are ready to analyse the effect of the enzyme, which reduces the barrier from —25 kcal/mol to —9 kcal/mol, with the first step (H20— H+ + OH-) as the... 

Exercise 9.1. Evaluate the energetics of the reaction of Fig. 9.2 in a nonpolar enzyme-active site. 

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