Stereoselective Alkylation with Asymmetric Reagents 2. The Active Center Sulphydryl Groups of Yeast Alcohol Dehydrogenase.

Yeast alcohol dehydrogenase is inactivated at different rates by the antipodes of α-iodopropionic acid and its amide; the D (+) antipodes react faster. The influence of coenzyme, substrate and pH on the reaction velocity were investigated. Under all conditions second order kinetics have been observed. Activation parameters for the alkylation of the SH groups with the different antipodes were calculated from the temperature dependence of the reaction rates. Large differences in the activation enthalpies (ΔΔH = 6.8 kcal/mole and 2.3 kcal/mole, respectively) were found for the reaction of yeast alcohol dehydrogenase with the different antipodes of α-iodopropionic acid and α-iodopropionamide. These were compensated for by differences in activation entropy of —18.4 and — 5.6 entropy units, respectively. These results are interpreted by assuming highly dissymmetric surroundings of the reacting SH groups favouring the D (+) antipodes in the transition state of the alkylation reaction. The negative activation entropy indicates that this favourable transition state may be attained only by restriction of the degrees of freedom. The relationship between the stereoselective chemical reactivity and the stereospecificity of the enzyme is discussed. [ABSTRACT FROM AUTHOR]