Free energy, amide hydrolysis

In the group of amide compounds, acetyl imidazole (1740 cm ) has a much greater free energy of hydrolysis (Stadtman, 1954) and a greater carbonyl frequency than ordinary am ides (1627 to 1673 cm ) the correlations between infrared carbonyl frequency and reactivity for the series acetylpyrrole, acetylimidazole, acetyltriazole, and acetyltetrazole and the analogous acetylbenzimidazole series have been presented by Otting (1956) and Staab (1956, 1957). 

As an example, experimental kinetic data on the hydrolysis of amides under basic conditions as well as under acid catalysis were correlated with quantitative data on charge distribution and the resonance effect [13]. Thus, the values on the free energy of activation, AG , for the acid catalyzed hydrolysis of amides could be modeled quite well by Eq. (5)... 

A new, more general, way to combine ab initio quantum mechanical calculations with classical mechanical free-energy perturbation approach (QM/FE approach) to calculate the energetics of enzyme-catalysed reactions and the same reaction in solution has been reported." The calculated free energies were in fairly good agreement with the experimental data for the activation energies of the first test case, amide hydrolysis in trypsin and in aqueous solution. 

Proteins are linear polymers formed by linking the a -carboxyl group of one amino acid to the a -amino group of another amino acid with a peptide bond (also called an amide bond). The formation of a dipeptide from two amino acids is accompanied by the loss of a water molecule (Figure 3.18). The equilibrium of this reaction lies on the side of hydrolysis rather than synthesis. Hence, the biosynthesis of peptide bonds requires an input of free energy. Nonetheless, peptide bonds are quite stable kinetically the lifetime of a peptide bond in aqueous solution in the absence of a catalyst approaches 1000 years. 

That proteolytic enzymes can indeed catalyze the reversal of proteolysis was shown by Bergmann and Fraenkel-Conrat in 1937 in their study of the synthesis of insoluble amides and anilides catalyzed by papain and bromelin. These studies have been extended recently by other investigators. 113,114 q hg enzymes displayed the same specificity in synthesis as they did in hydrolysis. Moreover, when the free energy of the reaction was lowered by the subseqeunt hydrolysis of the product rather than by precipitation, the synthetic reaction also occurred but the net result of the reaction was a hydrolysis. These experiments serve only as models since in vivo such insoluble products as the anilides are not formed nor would protein synthesis result in net hydrolysis. 

The enzymatic hydrolysis of these important co-amides of glutamic and aspartic acids is widespread in organisms. These enzymes have been reviewed by Zittle, and little more can be added here. Except in the renal production of urinary ammonia the hydrolytic cleavage of glutamine is probably an unimportant reaction, since uncoupled hydrolysis of these amides would involve a considerable loss of free energy as heat. 

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