Lecture 8 - Enzymes 2

Focus on Enzymes and Cell Biology. Discusses enzyme active sites, inhibitors, effects of inhibitors on reactions, and enzyme reactivity control.

Active Site: Location where substrates bind for enzymatic reactions. The active site is often a pocket or groove on the enzyme's surface formed by amino acids that are critical for the enzyme's activity, facilitating the conversion of substrates into products.
Enzyme Inhibition: Disruption of enzyme activity by small molecules or drugs that can prevent substrate binding or reduce enzymatic activity, impacting cellular metabolism and biochemical processes.
Drug Interaction: Many drugs act as enzyme inhibitors, impacting metabolic pathways; this could lead to therapeutic effects or adverse side effects, depending on the specificity and nature of inhibition.

Competitive: Inhibitor competes with substrate for the active site, often resembling the substrate's structure. Increasing substrate concentration can overcome this type of inhibition.
Uncompetitive: Inhibitor binds only to the enzyme-substrate complex, preventing the complex from releasing products, generally leading to a decrease in maximum reaction velocity (Vmax).
Mixed: Inhibitor can bind to either free enzyme or the enzyme-substrate complex, affecting both the binding of substrate and product formation.
Noncompetitive: A type of mixed inhibition where the inhibitor does not prevent substrate binding but reduces the rate of reaction.
Irreversible: Covalent bond formation that permanently inactivates the enzyme, often through modifications like alkylation of active site residues.

Composed of critical residues often dispersed in the sequence but close spatially, crucial for substrate specificity and enzyme functionality.
The active site environment can differ from the surrounding solution properties (e.g., hydrophobic regions can bind nonpolar substrates effectively).
Essential for enzyme function; mutations can impair activity, leading to diseases or metabolic dysfunctions.

Ethanol as a Competitive Inhibitor: Acts in methanol poisoning cases by competing for the same active site of alcohol dehydrogenase, preventing the formation of toxic metabolites like formaldehyde.
DFP as an Irreversible Inhibitor: Is a nerve agent that irreversibly inhibits acetylcholinesterase, resulting in prolonged neurotransmitter action at synapses, leading to overstimulation of muscles and potential respiratory failure.

Availability of Enzymes: The regulation of enzyme quantities is controlled at a genetic level through gene expression and the synthesis of mRNA and proteins.
Allosteric Regulation: Involves binding of effector molecules to sites other than the active site, causing a conformational change in the enzyme, which can activate or inhibit activity depending on the nature of the effector.
Covalent Modifications: Include processes like phosphorylation (addition of a phosphate group) and dephosphorylation (removal of a phosphate group), which serve as on/off switches for enzyme activity and are often mediated by other enzymes like kinases and phosphatases.

Multiple regulatory strategies exist to modulate enzyme function, including enzyme isozymes for tissue-specific action and adaptive responses to metabolic demands. Allosteric effects and reversible covalent modifications are central to controlling enzyme activity efficiently, allowing organisms to respond to environmental changes and maintain homeostasis effectively.