Adaptations of enzymes for regulation of catalytic function.

1. Enzymes must not only be extremely effective catalysts, but must also be the operating components of very sensitive and sophisticated regulatory systems. Appropriate evolutionary adjustment of the properties of different enzymes causes the sites that bind typical metabolic intermediates to be only partially saturated in vivo, thus allowing flexibility for control by variation in ligand concentration. In contrast, sites that bind such coupling agents as the pyridine and adenine nucleotides seem to be virtually saturated. Thus the ratios, rather than the absolute concentrations, of these compounds are important in metabolic regulation. This type of response is esstial to the function of these compounds simultaneously as thermodynamic energy transducers and modifiers in the kinetics regulatory system. 2. Reaction orders of two to four are frequently encountered. They appear to be essenital to biochemical homoeostasis, which is the maintenance of nearly constant substrate concentrations at the expense of wide variation in flux rates. 3. The strategies of enzyme adaptation are general, but the actual adaptations of enzymes are highly specific, reflecting the place of the enzyme in a metabolic sequence, the place of the sequence in the metabolism of the cell and, in complex organisms, the function of the cell, and of the organ or tissue of which it is a part, in the organism. Patterns of adaptation must be almost infinitely varied. A few are presently known in outline, but probably none as yet in detail. Several examples are discussed.