Enzyme Inhibition Types

Competitive Inhibition

• Competitive inhibitors are structurally similar to the substrate and bind reversibly at the active or catalytic site.
• The effect of competitive inhibitors can be reversed by increasing the substrate concentration.
• Competitive inhibitors increase the apparent Km for a given substrate, requiring more substrate to achieve half maximal velocity.

Allosteric Inhibition

• Small organic molecules bind to a specific site away from the catalytic site.
• Conformational changes in the protein structure lead to decreased enzyme activity.
• Allosteric inhibitors decrease the enzyme's affinity for its substrate (increase Km), decrease maximal catalytic activity (decrease Vmax), or both.

Feedback Inhibition

• Inhibition of the activity of an enzyme in a pathway by the end products of that pathway.
• End products bind to an allosteric site on the regulatory key enzyme.
• Prevents the accumulation of unwanted amounts of metabolic end products.

Irreversible Enzyme Inhibition

• Inhibitor effects are permanent, often by destroying or modifying the enzyme.
• Examples include denaturing agents, antienzymes, and inhibitors that block chemical groups.

Effect of Substrate Concentration

• The velocity of the reaction increases as substrate concentration increases, up to a point of enzyme saturation.
• The Michaelis constant (Km) is the substrate concentration that produces half the maximal velocity (Vmax).
• A smaller Km reflects a higher affinity of the enzyme for its substrate, and vice versa.

Effect of Temperature

• Enzyme activity stops at 0°C due to molecule movement inhibition.
• As temperature rises, reaction velocity increases up to the optimum temperature due to increased kinetic energy and collisions.
• Activity stops around 70°C due to enzyme protein denaturation.
• Optimum temperatures vary: ~37°C for most animal enzymes, ~50°C for plant enzymes.

Effect of pH

• Each enzyme has an optimal pH for maximal activity.
• Activity decreases as pH deviates from the optimum.
• Slight pH changes alter substrate and catalytic site charges, impacting activity.
• Extreme pH changes cause denaturation and irreversible inhibition.
• Most enzymes have optima between pH 5 and 9, with exceptions like pepsin (optimum pH 2).

Clinically Important Enzymes and Diagnostic Applications

• Acid phosphatase: Red cells and prostate, used in diagnosing prostate cancer.
• Alanine aminotransferase (ALT): Liver, used for assessing hepatic parenchymal diseases.
• Alkaline phosphatase: Liver, bone, intestinal mucosa, and placenta; used in diagnosing bone diseases and hepatobiliary diseases.
• Amylase: Salivary glands and pancreas, used in diagnosing parotitis and pancreatitis.
• Aspartate aminotransferase (AST): Liver, skeletal muscle, and heart; used in diagnosing hepatic parenchymal diseases, muscle, and cardiac diseases.
• Creatine kinase: Skeletal muscle and heart, used in diagnosing muscle diseases and myocardial infarction.
• Lactate dehydrogenase (LDH): Heart, liver, skeletal muscle, erythrocytes, platelets, and lymph nodes; used in diagnosing hemolysis, hepatic parenchymal diseases, and as a tumor marker.