Enzyme Inhibition Overview

Enzyme Inhibition

• Enzyme inhibitors are compounds that reduce the speed of an enzyme-catalyzed reaction by binding to the enzyme.
• Two main types of enzyme inhibitors exist: reversible and irreversible inhibitors.

Reversible Inhibitors

• These inhibitors bind non-covalently to the enzyme, allowing for dissociation.
• Subcategories of reversible inhibitors include competitive inhibitors.

Competitive Inhibitors

• Competitive inhibitors compete with the substrate for binding to the enzyme's active site.
• These inhibitors generally resemble the substrate in structure.
• Increasing substrate concentration can overcome competitive inhibition.
• Competitive inhibition increases the K_M value, but does not alter V_max.
• Methotrexate is an example of a competitive inhibitor, which is an anticancer drug that inhibits the enzyme dihydrofolate reductase.

Non-competitive Inhibitors

• Non-competitive inhibitors bind to a site on the enzyme other than the active site, affecting the enzyme's ability to function.
• Non-competitive inhibitors do not resemble the substrate.
• Non-competitive binding reduces V_max, but does not affect K_M.
• Cyanide is an example of a non-competitive inhibitor, which inhibits the enzyme cytochrome oxidase.

Irreversible Inhibitors

• Irreversible inhibitors bind covalently or very tightly to the enzyme's active site, permanently inactivating it.

Allosteric Enzymes

• Allosteric enzymes have multiple binding sites, including regulatory sites.
• These sites can bind activators or inhibitors, affecting enzyme activity.
• Allosteric enzymes are often involved in the initial steps of metabolic pathways and frequently catalyze irreversible reactions.

Isoenzymes

• Isoenzymes are enzymes that catalyze the same reaction but have different structures.
• Isoenzymes vary in their structure and their affinity for the substrate.
• Isoenzymes exhibit variations in their resistance to inhibitors and mobility in electrical fields (electrophoresis).
• Lactate dehydrogenase (LDH) is an example, with five distinct isoenzymes having different subunit compositions.

Regulation of Enzyme Activity

• Allosteric regulation involves feedback and feed-forward mechanisms.
• Covalent modification, including phosphorylation and dephosphorylation, also regulates enzyme activity.

Enzymes in Clinical Diagnosis

• Elevated enzyme activity in the blood may indicate tissue damage, which is frequently useful in diagnosis and prognosis.
• Plasma enzymes are sensitive indicators of tissue damage or disease.
• Alanine aminotransferase (ALT) levels can indicate liver damage when elevated.

Explore the fascinating world of enzyme inhibition, focusing on both reversible and irreversible inhibitors. Learn about competitive and non-competitive inhibitors, their mechanisms, and examples of their applications in medicine. Understand how these inhibitors affect enzyme activity and the implications for various biological processes.