Regulation of enzyme activity
There are several means by which the activity of a particular enzyme is specifically regulated.
Irreversible covalent Activation / Zymogen activation
Some enzymes are secreted in an inactive form called Proenzymes or zymogens. At the site of action specific peptide bonds are hydrolysed either enzymatically or by PH changes to convert it into active form, e.g. Pepsinogen € pepsin, Trypsinogen€ trypsin, plasminogen€ plasmin. After hydrolysis when it is activated, it cannot be reconverted into proenzyme form.
Reversible Covalent Modification
By addition of or removal of phosphate or adenylate, certain enzymes are reversibly activated and inactivated as per the requirement. Protein kinase of muscle phosphorylate phosphorylase kinase, glycogen synthetase by making use of ATP.
Allosteric Modulation
In addition to simple enzymes that interact only with substrates and inhibitors, there is a class of enzymes that bind small, physiologically important molecules and modulate activity in ways other than those described above. These are known as allosteric enzymes; the small regulatory molecules to which they bind are known as effectors. Allosteric effectors bring about catalytic modification by binding to the enzyme at distinct allosteric sites, well removed from the catalytic site, and causing conformational changes that are transmitted through the bulk of the protein to the catalytically active site(s).
The hallmark of effectors is that when they bind to enzymes, they alter the catalytic properties of an enzyme's active site. Those that increase catalytic activity are known as positive effectors. Effectors that reduce or inhibit catalytic activity are negative effectors.
There are two ways that enzymatic activity can be altered by effectors: the Vmax can be increased or decreased, or the Km can be raised or lowered
Feedback inhibition
In allosteric regulation in which end products inhibit the activity of the enzyme is called”
feedback inhibition”.
A high conc. D typically inhibits conversion of AÆ B.
This involves not simple backing up of intermediates but the activity of D to bind to
and inhibit E1. D thus acts as negative allosteric affector or feedback inhibitor of E1.
The kinetics of feedback inhibition cay be competitive, mixed, etc. It is the
commonest way of regulation of a biosynthetic pathway. Feedback regulation generally
occurs at the earliest functionally irreversible step unique in the biosynthetic pathway