Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 2 49Enzymatic reactions are as a whole multistage processes. Thesubstrate S initially binds non-covalently to the enzyme E at a special sitecalled the active site. The reversible complex of substrate S and enzyme Eis called the Michaelis-Menten complex. It provides the propercombination of reactant and catalytic groups in the active site of theenzyme (equation 1):E+SK 1K-1Equation 1ESIn the active site, after the formation of the Michaelis-Mentencomplex, the chemical reaction step takes place and the enzyme substratecomplex breaks down in a slower second step to yield the free enzyme Eand the reaction product P (equation 2):ESK 2K-2Equation 2E+PIn this model, the second reaction is slower and therefore is ratelimiting for the overall reaction. From this it follows that the overall rateof enzyme-catalyzed reactions must be proportional to the concentrationof the ES complex. At any given instant in an enzyme catalyzed reaction,the enzyme exists in two forms, the free or uncombined form E and thecombined form, the ES complex. At low [S], most of the enzyme will bein the uncombined form E. Under these conditions the rate will beproportional to [S] because the equilibrium of equation 1 will be shiftedtowards the formation of more ES as [S] is increased. The maximuminitial rate of the catalyzed reaction (V MAX ) is observed when virtually allof the enzyme is present as ES complex and the concentration of E isextremely small. Under those conditions, the enzyme is "saturated" with itssubstrate, Further increases in [S] will not cause any increase in rate. Afterthe ES complex breaks down to give the product P, the enzyme is free tocatalyze the transformation of another substrate molecule. The