The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
Most enzymes achieve catalytic perfection due to the charged groups present on their surface that orient and steer the substrate into the active site. Some other enzymes have a specific active site arrangement, contributing to catalytic perfection. In enzymes such as superoxide dismutase, metal ions, such as copper and zinc, in the active site and charged amino acids, such as arginine, close to the active site speed up the conversion of superoxide anion into oxygen and hydrogen peroxide. Random mutations in enzymes favor such interactions with their substrates, and enzymes with higher efficiency are naturally selected over time.
Perfect enzymes not only catalyze highly efficient reactions but can also help protect cells from harmful reaction intermediates. For example, triose phosphate isomerase (TPI) is an enzyme in the glycolytic pathway that catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). The slow conversion of DHAP into G3P forms an enediol intermediate that eventually decomposes into a toxic compound. As TPI is a catalytically perfect enzyme, it speeds up the reaction and quickly transforms the intermediate into the product, avoiding undesirable compounds. So far, very few enzymes have evolved to be catalytically perfect. Most enzymes are moderately efficient.
