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When enzymes contain more than one active site, the binding of a substrate molecule to the first site may influence substrate binding to a second site.
Binding of the second substrate may influence binding of a third, and so on. This phenomenon is called cooperativity.
The influence may be positive in that binding of the first substrate molecule facilitates binding of subsequent substrate molecules (called “positive cooperativity”) or the influence may be negative in that binding of a second or subsequent substrate molecule occurs less readily than binding of the first (called “negative cooperativity”).
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In a sense, the substrate itself is acting as either a positive or negative effector for the enzyme. These relationships are depicted in Figure 8-24.
Cooperative effects are not restricted to enzymes but are observed with other proteins. We considered the cooperativity that exists among the globin chains of hemoglobin, a cooperativity that facilitates successive binding of oxygen molecules to the alpha and beta globin chains (i.e., positive cooperativity).
Both cooperative effects involving active sites on neighboring subunits of an enzyme and true allosteric effects involving regulatory sites may occur in a single enzyme molecule. A case in point is that of cytidine triphosphate synthetase, an enzyme involved in nucleic acid metabolism and consisting of four sub- units.
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Two of these subunits contain active sites that bind the substrate glutamine and the other two have regulatory sites that bind GTR When glutamine is bound to the active site of one subunit, a conformational change transmitted through the enzyme to another subunit renders the latter’s active site unable to bind to glutamine (i.e., negative cooperativity).
On the other hand, when GTP is bound to the regulatory site of one subunit, this has a positive effect on glutarnine binding but it negatively affects GTP binding at the other regulatory site. In other words, the effector GTP serves to activate catalysis but to inhibit further GTP binding.
