Enzyme Cofactors Some enzymes require cofactors to be active. Enzyme is protein only Example: lysozyme Enzyme Active site Some enzymes require cofactors to be active. Cofactors are a nonprotein component of an enzyme. Cofactors can be: organic molecules (coenzymes). inorganic ions (e.g. Ca2+, Zn2+). Cofactors may be: Permanently attached, in which case they are called prosthetic groups. Temporarily attached coenzymes, which detach after a reaction, and may participate with another enzyme in other reactions. Enzyme + prosthetic group Example: flavoprotein + FAD Active site Prosthetic group Enzyme Enzyme + coenzyme Example: dehydrogenases + NAD Coenzyme Enzyme Active site

Enzyme Inhibitors Enzymes can be deactivated by enzyme inhibitors. There are two types of enzyme inhibitors: Reversible inhibitors are used to control enzyme activity. There is often an interaction between the substrate or end product and the enzymes controlling the reaction. Irreversible inhibitors bind tightly and permanently to the enzymes destroying their catalytic activity. Irreversible inhibitors usually covalently modify an enzyme. Many drug molecules are enzyme inhibitors. Native arsenic Mercury Photo: US EPA Some heavy metals (above) are examples of poisons which act as irreversible enzyme inhibitors.

Irreversible Enzyme Inhibitors Substrate Enzyme Some heavy metals, such as cadmium (Cd), arsenic (As), and lead (Pb) act as irreversible enzyme inhibitors. They bind strongly to the sulphydryl (- SH) groups of the protein, destroying its catalytic activity. Most heavy metals, e.g. arsenic, act as non-competitive inhibitors. Mercury (Hg) is an exception. It acts as a competitive inhibitor, binding directly to a sulphydryl group in the active site of the papain enzyme. Heavy metals are retained in the body, and lost slowly. The lipothiamide pyrophosphatase enzyme with substrate bound to its active site. Arsenic binds to the enzyme and causes its shape to change, preventing the substrate from binding to the active site. As Poisons, such as arsenic (As), act as an irreversible enzyme inhibitor. It binds to the lipothiamide pyrophosphatase enzyme altering its shape so the substrate cannot bind.

Reversible Inhibitors Reversible inhibitors are used to control enzyme activity. There is often an interaction between the substrate or end product and the enzymes controlling the reaction. Buildup of the end product or a lack of substrate may deactivate the enzyme. Competitive inhibition involves competition for the active site. Noncompetitive inhibitors work either to slow down the rate of reaction, or block the active site altogether and prevent its functioning (allosteric inhibition). Enzyme Competitive inhibition Competitive inhibitor blocks the active site. The substrate cannot bind. S S Noncompetitive inhibition The substrate can still bind to the active site but the rate of reaction is lowered. Enzyme Noncompetitive inhibitor Allosteric enzyme inhibitor The substrate cannot bind to the active site because the active site is distorted. Noncompetitive inhibitor Enzyme S No inhibition S Enzyme Substrate