Enzyme Catalysis: Mechanisms, Cofactors, and Regulation
Factors in Enzyme Catalysis
Proximity and Orientation
Enzymes act by increasing the effective concentrations of substrates, bringing them closer with appropriate guidance of reactive groups.
Surface Phenomena
The properties of the active site can be considerably different from the surrounding medium and more favorable for a particular reaction to occur.
Strain and Distortion Factors
The presence of groups capable of providing reactive mechanisms of lower activation energy. These act by general acid-base catalysis or covalent catalysis.
Coenzymes and Cofactors
Many enzymes are conjugated proteins in nature and contain a non-protein component called a cofactor. The cofactor is usually essential for enzymatic catalysis and, together with the enzyme protein, or apoenzyme, constitutes the holoenzyme.
The chemical nature of the cofactor is varied: they can be metal ions (in the case of metalloenzymes), or organic molecules called coenzymes. Some enzymes require one or more metal ions and a coenzyme to carry out their catalytic function.
When the cofactor is strongly joined to the apoenzyme by covalent bonds, it is called a prosthetic group. Coenzymes are synthesized by the body from simpler molecules, which often cannot be produced by the body itself, so they must be supplied through food. These exogenous factors required for the synthesis of coenzymes are known as micronutrients, such as water-soluble vitamins.
Regulation of Enzyme Activity
Effect of pH and Temperature on Enzymatic Reaction Rates
Typically, the activity of an enzyme is maximum around a determined pH value, the optimum pH, where the protein conformation and state of ionization of amino acid residues of the active site are suitable for recognition and processing of the substrate. Often, the optimum pH of an enzyme reflects the pH of the environment in which it exerts its physiological action.
The effect of temperature on the rate of enzymatic reactions is also complex because at least two factors are involved: as in any chemical reaction, an increase in temperature causes an increase in reaction rate; however, a rise in temperature also accelerates the denaturation of the protein.
Enzyme Inhibition
In all organisms, the activation or inhibition of some key enzymes in different metabolic pathways contributes decisively to the regulation of flow through such pathways. Inhibitors are classified as irreversible, which join the enzyme by covalent bonds and inactivate it permanently, and reversible, which do not form covalent links and, under appropriate conditions, can be displaced from the protein, thereby restoring native kinetic characteristics.
Types of Reversible Inhibitors:
- Competitive Inhibitors: These have a structure very similar to the substrate and are recognized by the enzyme’s active site.
- Non-competitive Inhibitors: These bind to specific sites on the enzyme molecule, distinct from the active site.
- Uncompetitive Inhibitors: These bind to the enzyme-substrate complex, forming a ternary enzyme-inhibitor-substrate complex.