Allosteric regulation and covalent modulation: The activity of enzymes are regulated by altering the catalytic activity of the enzymes. The mechanism of control of catalysis involves a changes in enzymes activity without a change in the total amount of enzymes synthesized. Allosteric regulation and covalent modulation are important mechanism of this type:
Allosteric regulation may have to functionally different bindings sites active site and an allosteric site (regulatory site) active site binds the substrate and catalyze the reaction while allosteric site binds another molecule called effector or modulator. Allosteric enzymes regulate the catalytic activity with the help of effector molecules which are of two types: Positive effector (Activator), Negative effector (inhibitor). Activator enhance enzyme activity while inhibitor inhibit enzyme activity. Binding of effectors causes and conformational changes in the allosteric enzymes which influence their catalytic activity. Regulatory sites of allosteric enzymes are specific to the product of the metabolic pathway.
As the metabolism proceeds, the concentration of the end product increases, the end product molecules act as negative effectors and bind to the regulatory sites of the allosteric enzymes. The effector binds non-covalently to the regulatory site of the enzyme. Therefore, inactivation of enzymes is reversible, on binding of the negative effector converts the inactive enzymes to their active form. Binding of positive effector molecule to the regulatory site of allosteric enzymes converts the inactive enzyme to its active form.
This is brought about by changes in the confirmation and structure of the enzyme. Enzyme Aspartate Transcarbonueylaseis (ATCase) is a good example of Allosteric regulation. The end product CTP binds to the allosteric site of the enzyme inhibiting activity of the enzyme. The inhibited activity of the enzyme is again stimulated at binding of ATP molecule at its regulatory site. So end product CTP acts as negative effector (inhibitors) and ATP acts as positive effector.
Activity of many enzymes is altered by the reversible making and breaking of a covalent bond between the enzyme and a small non-protein group. So covalent modification cause conformational changes in the enzymes. These conformational changes are brought about by covalent bonding of a phosphate group (phosphorylation) to the peptide chain or by removal of a small polypeptide chain by a process known as proteolysis. These covalent modifications stimulate the enzyme activity. For example the conversation of glycogen into glucose phosphate is catalyzed by an enzyme glycogen phosphorylase.
Glycogen phosphorylase is regulated by covalent modifications. Glycogen phosphorylase occurs in two forms: phosphorylase a, (the active form) and phosphorylase b, (the inactive form). Both two forms are inter convertible, phosphorylase b is converted into active phosphorylase a by covalent binding of phosphate groups. Phosphorylase kinase enzyme involved in this conversion.
Some covalent modification is caused by proteolysis which are irreversible. In proteolytic conversion, removal of a small peptide chain form the inactive enzyme converts it into active form. For example some digestive enzyme (such as trypsin and pepsin) synthesized in their inactive forms. (trypsinogen and pepsinogen). But they are converted in their active form by removal of a small polypeptide chain. Such as trypsinogen is converted to active trypsin by removal of six amino acids from the N-terminus of the inactive enzyme. Enterokinase enzyme involve in this process.