Enzymes II: Regulation and Inhibition

Comprehensive vocabulary flashcards covering reversible and irreversible enzyme inhibition, kinetics, allosteric regulation, covalent modifications, induction/repression, and limited proteolysis.

Inhibitor

A substance that can diminish the velocity of an enzyme-catalyzed reaction.

Irreversible inhibition

A form of inhibition where the inhibitor permanently and irreversibly blocks the active center or a binding site of the enzyme, preventing the enzyme from regaining catalytic activity even upon dilution of the enzyme-inhibitor complex.

Diisopropyl fluorophosphate (DFP, DIFP)

An irreversible enzyme inhibitor that permanently blocks active sites and serves as the chemical basis for certain insecticides.

Competitive inhibition

A type of reversible inhibition where a structural analogue of the substrate binds noncovalently exclusively to free enzyme ($E$) at the active center, increasing the apparent $K_m$ (requiring more substrate to reach $\frac{1}{2} V_{\max}$) without altering the maximal velocity ($V_{\max}$).

Noncompetitive inhibition

A type of inhibition where the inhibitor is not a structural analogue of the substrate and binds outside the active center to both free enzyme ($E$) and the enzyme-substrate ($ES$) complex, decreasing $V_{\max}$ while leaving $K_m$ unchanged.

Pravastin

A competitive inhibitor drug used in cholesterol synthesis regulation that acts as a structural analogue to compete with substrate binding.

Enzymes as drugs criteria

The requirements that therapeutic enzyme inhibitors must inhibit an enzyme specific to a particular metabolic pathway (in humans or bacteria) and exhibit minimum toxicity through pathogen specificity.

Allosteric enzymes

Enzymes possessing at least one additional regulatory binding site separate from the active center, typically composed of multiple subunits (quaternary structure) and displaying sigmoidal reaction velocity curves that do not conform to Michaelis-Menten kinetics.

Allosteric effectors (modulators)

Molecules that bind to a regulatory site outside of the active site (sometimes on a non-catalytic subunit) to alter the enzyme's affinity for substrate and/or modify its maximal catalytic activity, classified as positive (increasing activity) or negative (inhibiting activity).

Cooperative effect

A phenomenon in allosteric multi-subunit enzymes where the binding of substrate to one subunit increases the substrate affinity of the remaining subunits, producing a sigmoidal kinetics curve analogous to oxygen binding in hemoglobin.

Homotropic effector

An allosteric effector where the substrate itself functions as the regulatory molecule (most often positive), enhancing the catalytic activity of remaining substrate-binding sites and shifting $V_{\max}$ and/or $K_{0.5}$.

Heterotrophic effector

An allosteric effector molecule whose chemical identity is entirely different from the substrate of the regulated enzyme.

Feedback inhibition (Retroinhibition)

A rapid regulatory mechanism wherein an end product of a metabolic pathway acts as a heterotrophic effector by binding to an allosteric site on an upstream enzyme (typically Enzyme 1), inhibiting the initial irreversible step unique to the pathway.

Reversible covalent modification

A fast regulatory mechanism (seconds or minutes) responding to hormones and neurotransmitters, most frequently involving phosphorylation by protein kinases (transferring a phosphate from $ATP$) or dephosphorylation by phosphoprotein phosphatases (hydrolyzing phosphate as $HPO_4^{2-}$) on specific serine, threonine, or tyrosine residues.

Induction and repression

Mechanisms that regulate the total amount of active enzyme present in the cell by altering rates of enzyme synthesis (or degradation), usually controlling enzymes needed at specific developmental stages or physiological conditions (e.g., insulin inducing key enzymes in glucose metabolism).

Limited proteolysis

The irreversible post-translational activation of an inactive precursor protein (proenzyme or zymogen) into an active enzyme through selective cleavage of specific peptide bonds without complete destruction of the polypeptide chain.

Zymogen (pro-enzyme)

An inactive enzymatic precursor that requires specific irreversible proteolytic cleavage to be converted into its catalytically active form (examples include chymotrypsinogen, trypsinogen, and pepsinogen).