Principles of Catalytic Strategies and Enzyme Mechanisms

Vocabulary practice flashcards covering the principles of catalytic strategies, enzyme classification, kinetics, binding equilibria, cofactors, and mechanisms.

Enzymes

Biological catalysts that accelerate chemical reactions by decreasing their activation energy, achieving rate enhancement factors between $10^6$ to $10^{17}$ while remaining chemically unchanged at the end of the reaction.

What are the six (seven) groups based on the type of reaction catalysed? (Are divided into subgroups and further sub-divided)

1. Oxidoreductases,

2. Transferases,

3. Hydrolases,

4. Lyases,

5. Isomerases,

6. Ligases,

7. Translocases

Oxidoreductases

A large group of enzymes that catalyse oxidation-reduction (redox) reactions

$$AH_2 + B \rightarrow A + BH_2$$

Transferases

Transfer a specific functional group from one substrate to another

$AB + C \rightarrow A + BC$.

Hydrolases

Catalyse the hydrolysis of bonds (cleavage of bonds through the addition of water)

$$AB + H_2O \rightarrow AH + HO\text{-}B$$

Lyases

Cleave C-C, C-O, C-N, and other bonds by elimination, leaving double bonds, or conversely add groups across double bonds

$$AB \rightarrow A + B$$

Isomerases

Catalyse geometric or structural changes within a single molecule

$$A \rightarrow \text{isoA}$$

Ligases

Join two substrate molecules together in a reaction coupled with the hydrolysis of ATP or another nucleoside triphosphate

$$A + B \rightarrow AB$$

Translocases

Catalyses the movement of ions or molecules across biological membranes.

Ribozymes

RNA molecules that possess catalytic activity, i.e. enzymes thar are RNA molecules

Coenzymes

Organic molecules that function as transient carriers of specific atoms or functional groups during enzymatic reactions

• e.g. TPP (thiamine pyrophosphate, FAD, NAD, CoA, PLP, Biotin, and THF

Catalytic Power

The ratio of the rate of the enzyme-catalysed reaction to that of the uncatalyzed reaction ($k_{\text{cat}} / k_{\text{uncat}}$)

• reaching values up to $10^{17}$ in enzymes such as urease.

Specificity (substrate and reaction)

“Preference” of an enzyme for a substrate

• e.g. maltase enzyme is specific for the hydrolysis of maltose and cannot hydrolyse isomaltose

Diffusion-Limited Enzyme

An enzyme whose catalytic rate is so rapid that the rate-limiting step is the physical diffusion of substrate into the active site or product diffusion out (e.g., carbonic anhydrase with a $k_{\text{cat}}$ of $600000\,\text{s}^{-1}$).

The diffusion rate of the substrate limits the

Dissociation Constant ($K_d$)

An equilibrium constant quantifying protein-ligand binding affinity, defined as $K_d = \frac{[P][L]}{[PL]} = \frac{K_{\text{off}}}{K_{\text{on}}} = \frac{1}{K_a}$, where $\Delta G = \Delta H - T\Delta S = -RT\ln(K_d)$.

Induced-Fit Binding Mechanism

A mechanism of molecular recognition where initial ligand binding ($P_1 + L \rightleftharpoons P_1\cdot L$) induces a subsequent conformational change in the enzyme ($P_1\cdot L \rightleftharpoons P_2\cdot L$).

Conformational-Selection Binding Mechanism

A mechanism of molecular recognition where the protein naturally fluctuates between conformational states ($P_1 \rightleftharpoons P_2$), and the ligand selectively binds to and stabilizes (equilibrium favours one side of the reaction) one specific conformation ($P_2 + L \rightleftharpoons P_2\cdot L$).

Transition State

The highest point on the free-energy reaction pathway between substrate and product where chemical bonds are actively forming and breaking, persisting only for approximately the duration of a molecular bond vibration ($10^{-15}\,\text{s}$).

Hammond Postulate

The principle stating that transition states and adjacent reaction intermediates that are close in energy will possess similar molecular structures and geometries.

Enthalpic 'Trapping Out' of Entropy

The mechanism wherein the substantial loss of conformational entropy incurred upon substrate binding is compensated by favorable non-covalent binding interactions formed with the enzyme active site.

Electrostatic Steering

An evolved distribution of electric charges on an enzyme's surface that guides charged substrate molecules directly into the active site cavity, minimizing unproductive collisions.

Aldolase

An enzyme representative of covalent catalysis that catalyses the conversion of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

Alcohol Dehydrogenase

A zinc-requiring ($Zn^{2+}$) enzyme that uses metal-ion catalysis and NAD coenzyme to interconvert ethanol and acetaldehyde.

Chymotrypsin

A serine proteinase (EC 3.4.21.1) that utilizes general acid-base catalysis to cleave peptide bonds on the carboxyl-terminal side of aromatic residues (tryptophan, tyrosine, and phenylalanine).

Allosteric Control

A regulatory mechanism not describable by standard Michaelis-Menten kinetics, where the binding of effectors (activators or inhibitors) at sites distinct from the catalytic center shifts the sigmoidal activity profile of an enzyme.

Arginine Side Chain

A basic, guanidinium-bearing amino acid side chain with a $pK_a$ of approximately $12.5$, remaining positively charged across physiological pH ranges and serving in substrate binding and electrostatic steering.

Aspartic Acid Side Chain

An acidic amino acid side chain possessing a carboxyl group with a $pK_a$ of approximately $3.9$ to $4.0$, participating in acid-base catalysis and electrostatic interactions.

AhpD (Alkylhydroxyperoxidase D)

An alkylhydroxyperoxidase from Mycobacterium tuberculosis having a trimeric quaternary structure and a novel topology, whose catalytic mechanism relies on an active-site network of C130, C133, H132, H137, and E118 to reduce organic hydroperoxides.