Enzymes Notes

Cofactors

• Cofactors are helper molecules that bind at the active site of an enzyme to activate it.
• Essential dietary minerals often serve as cofactors.
• If a cofactor is an organic molecule, it is called a coenzyme.
• Vitamins are usually coenzymes.

Enzyme Inhibitors

• Enzyme inhibitors are chemicals that impede the function of enzymes by binding to them.
• There are three types of inhibitors:
  • Competitive: Hydrogen bonded and reversible.
  • Noncompetitive: Hydrogen bonded and reversible.
  • Irreversible: Covalently bonded and non-reversible.

Competitive Inhibitors

• Competitive inhibitors resemble the shape of the substrate.
• They prevent substrates from binding to the active site by occupying the active site themselves.

Noncompetitive Inhibitors

• Noncompetitive inhibitors bind to a separate part of the enzyme.
• This binding causes the enzyme to change shape, which in turn alters the active site.
• Due to the change in the active site's shape, the substrate can no longer bind effectively.

Competitive Inhibition Example

• Beta blockers, used to manage high blood pressure, are competitive inhibitors.
• They work by preventing adrenaline, a protein hormone, from binding to its receptor on heart cells, thus decreasing heart rate.
• Beta blockers occupy the active site of the receptor-enzyme.

Reversible Inhibitors: Overcoming Inhibition

• To overcome competitive inhibition:
  • Increase the concentration of the substrates so that they outnumber the inhibitors, making it more likely for substrates to bind to the active site.
  • Dilute the solution, as the weak hydrogen bonds in reversible inhibitors mean they do not typically undergo a chemical reaction.

Irreversible Inhibition

• Irreversible inhibitors establish permanent covalent bonds with an enzyme, causing a change in its shape and inactivating it.
• These inhibitors are present in natural poisons utilized by organisms for defense, as well as in manufactured pesticides.
• Artificial irreversible inhibitors are employed in medicine to destroy malfunctioning cells in organisms (e.g., chemotherapy for cancer).

Irreversible Inhibition: Covalent Bonds

• Traditional reversible drugs are in equilibrium with their target, continually binding, unbinding, and rebinding.
• Covalent irreversible drugs bind specifically to a drug target and form a precisely directed, permanent bond with their target.

Irreversible Inhibition: Ribosome Inhibiting Proteins (RIPs)

• Ribosome inhibiting proteins (RIPs) are irreversible inhibitors.
• Ricin, a protein found in castor beans, irreversibly binds to glycoproteins.
• Upon binding, ricin changes the shape of ribosomes, preventing them from synthesizing new proteins, ultimately leading to cell death.