A highly specialized enzyme having a regulatory (controlling) function through its capacity to undergo a change in its catalytic activity. There exist two majoi types of regulatory enzymes: (1) covalently modulated enzymes, and (2) allosteric enzymes. Covalently modulated enzymes are enzymes that can be interconverted between active and inactive (or less active) forms by the covalent attachment (or removal) of a modulating metabolite by other enzymes. Hence the activity of one enzyme can, under certain conditions, be regulated by other enzymes. Glycogen phosphorylase, an oligomeric protein with four major subunits (tetramer), is a classic example of a covalently modulated enzyme. The enzyme occurs in two forms: (1) phosphorylase a, the more active form, and (2) phosphorylase b, the less active form. In order for the enzyme to possess jnaximal catalytic activity (i.e., be phosphorylase a) certain serine residue on all four subunits must have a phosphate covalently attached. If, due to other regulatory signals it has received, the enzyme phosphorylase phosphatase hydrolytically cleaves and removes the phosphate group from the four subunits, the tetramer dissociates into the inactive (or much less active) dimer, phosphorylase b. Another enzyme, phosphorylase kinase, is able to rephosphorylate the four specific serine residues of the four subunits at the expense of ATP and regenerate the active phosphorylase a tetramer.
AUosteric enzymes are enzymes that possess a special site on their surfaces that is distinct from the enzyme’s catalytic site and to which specific metabolites (called effectors or modulators) are reversibly and noncovalently bound. The allosteric binding site is as specific for a particular metabolite as is the catalytic site, but it cannot catalyze a reaction, only bind the effector. The binding of the effector causes a conformation change in the enzyme such that its catalytic activity is impaired or stopped. Allosteric enzymes are normally the first enzymes in, or are near the beginning of, a multienzyme system. The very last product produced by the multienzyme system (the end product) may act as a specific inhibitor of the allosteric enzyme by binding to that enzyme’s allosteric site. The binding consequently causes a conformation change to occur in the enzyme, which inactivates it. A classic example of an allosteric enzyme in a multienzyme sequence is the enzyme L-threonine dehydratase, which is the initial enzyme in the enzyme sequence that catalyzes the conversion of L-threonine to L-isoleucine. This reaction occurs in five enzyme-catalyzed steps. The end product, L-isoleucine, strongly inhibits L-threonine dehydratase, the first enzyme in the five-enzyme sequence. No other intermediate in the sequence is able to inhibit the enzyme. This kind of repression is called feedback or end-product inhibition.
It should be noted that allosteric control may be negative (as in the example above) or positive. In positive control the effector binds to an allosteric site and stimulates the activity of the enzyme. Furthermore, some allosteric enzymes respond to two or more specific modulators with each modulator having its own specific binding site on the enzyme. An allosteric enzyme that has only one specific modulator is called monovalent whereas an enzyme responding to two or more specific modulators is called polyvalent. Combinations of the above possibilities could lead to very fine tuning of the enzymes involved in the synthesis and/or degradation of metabolites. Note that in the two examples above, the common denominator is the structural change that occurs upon execution of the mechanism.