Week 5: Enzyme Kinetics, Inhibition Mechanisms, and Allosteric Regulation

Vocabulary practice flashcards covering enzyme catalysis, kinetics, Michaelis-Menten parameters, Lineweaver-Burk analysis, reversible and irreversible inhibition mechanisms, and allosteric enzyme regulation based on MD-101 lecture notes.

Catalyst

A substance that accelerates the rate of a chemical reaction without being consumed or changed at the end of the reaction, enabling the system to reach equilibrium much faster.

Enzyme Specificity

The ability of an enzyme to distinguish its specific substrate from other molecules that possess similar chemical structures.

Trypsin

A proteolytic enzyme that cleaves peptide bonds specifically after Lys or Arg residues, unless the Lys or Arg residue is directly followed by Pro.

Thrombin

A protease that hydrolyzes Arg-Gly peptide bonds specifically and exclusively within the amino acid sequence Lys-Val-Pro-Arg-Gly-Ser.

"Lock and key" Model

A model of enzyme-substrate binding proposed by Emil Fischer in 1890 stating that the active site of the enzyme and the substrate possess complementary geometric shapes that fit precisely together.

Induced Fit Model

A model of enzyme-substrate binding proposed by Daniel E. Koshland Jr in 1958 stating that the active site undergoes conformational changes upon substrate binding to form the active enzyme-substrate complex.

First-Order Reaction

A chemical reaction whose rate is directly proportional to the concentration of a single reactant.

Pseudo-First-Order Reaction

A second-order reaction involving two reactants that behaves kinetically as a first-order reaction because the concentration of one substrate is in vast excess relative to the other.

Turnover Number ($k_{\text{cat}}$/Catalytic Constant)

The rate constant ($k_2$) of the rate-limiting step in an enzymatic reaction, representing the number of substrate molecules converted to product per unit of time by a single enzyme molecule when saturated with substrate.

Maximal Velocity ($V_{\max}$)

The maximum initial reaction velocity achieved when all enzyme active sites are completely saturated with substrate.

Michaelis Constant ($K_M$)

The substrate concentration at which the reaction velocity is half of its maximal velocity ($\frac{1}{2}V_{\max}$); defined as $K_M = \frac{k_{-1} + k_2}{k_1}$, where a low value indicates strong binding and a high value indicates weak binding.

Lineweaver-Burk Plot

A double-reciprocal plot of $\frac{1}{V_0}$ versus $\frac{1}{[S]}$ displaying a linear relationship with a slope of $\frac{K_M}{V_{\max}}$, a y-intercept of $\frac{1}{V_{\max}}$, and an x-intercept of $-\frac{1}{K_M}$.

Irreversible Inhibitor

An inhibitor that dissociates very slowly from its target enzyme because it binds tightly through covalent or strong noncovalent interactions, permanently inactivating the enzyme.

Penicillin

An irreversible inhibitor that acts by covalently modifying the bacterial enzyme transpeptidase, preventing bacterial cell wall synthesis.

Aspirin

An irreversible inhibitor that covalently modifies the enzyme cyclooxygenase, reducing the synthesis of inflammatory signaling molecules.

Competitive Inhibitor

A reversible inhibitor structurally similar to the substrate that binds directly to the enzyme active site, increasing the apparent $K_M$ while leaving $V_{\max}$ unchanged, which can be overcome by increasing substrate concentration.

Inhibition Constant ($K_I$)

The equilibrium dissociation constant describing the interaction between an enzyme and an inhibitor, defined as $K_I = \frac{[E][I]}{[EI]}$.

Uncompetitive Inhibitor

A reversible inhibitor that binds exclusively to the enzyme-substrate ($ES$) complex at a site distinct from the active site, resulting in a decrease in both $V_{\max}$ and the apparent $K_M$.

Noncompetitive Inhibitor

A reversible inhibitor that binds to both the free enzyme ($E$) and the enzyme-substrate ($ES$) complex at a distinct regulatory site, decreasing $V_{\max}$ while leaving $K_M$ unchanged.

Half Maximal Inhibitory Concentration ($\text{IC}_{50}$)

The concentration of an inhibitor required to reduce an enzymatic or biological response to $50\%$ of its baseline value measured in the absence of the inhibitor.

Cheng–Prusoff Equation

An equation formulated by Yung-Chi Cheng and William Prusoff defining the relationship between the $\text{IC}_{50}$ and the inhibition constant ($K_i$) for a competitive inhibitor: $\text{IC}_{50} = K_i\left(1 + \frac{[S]}{K_M}\right)$.

Suicide Inhibitor

A specialized class of irreversible active-site inhibitors that are processed through the initial steps of the normal enzymatic reaction to generate a highly reactive compound that binds irreversibly to the enzyme, such as the anticancer drug fluoro-uracil.

Allosteric Enzymes

Regulatory enzymes that undergo conformational changes upon reversible, non-covalent binding of effectors at sites other than the active site, displaying sigmoidal kinetics that diverge from hyperbolic Michaelis-Menten kinetics.

Homotropic Enzyme

A regulatory allosteric enzyme for which the natural substrate and the regulatory modulator are identical molecules.

Heterotropic Enzyme

An allosteric enzyme whose regulatory modulator is a molecule distinct from the enzyme's substrate.

$$K_{0.5}$$

The substrate concentration required to achieve half-maximal reaction velocity ($\frac{1}{2}V_{\max}$) in an allosteric enzyme, which shifts to lower concentrations with a positive modulator and higher concentrations with a negative modulator.