Enzymes: Structure and Function

• Enzymes are organic compounds acting as catalysts for biochemical reactions
• Catalysts increase reaction rates without being consumed
• Greek roots of enzyme are "en" (in) and "zyme" (yeast)
• Each human cell possesses thousands of specific enzymes for cellular reactions
• Enzymes accelerate cellular reactions up to millions of times faster
• Enzymes are not consumed

Enzyme Structure

• Enzymes have two general structure classes: simple and conjugated
• Simple enzymes consist solely of protein
• Conjugated enzymes incorporate a nonprotein part in addition to a protein
• Apoenzyme is the protein part of a conjugated enzyme
• Cofactor is the nonprotein part, which can be a small organic molecule or inorganic ion
• Metal ions such as Zn2+, Mg2+, Mn2+, and Fe2+, or nonmetal ions like Cl- can be cofactors
• Coenzyme is a small organic molecule serving as a cofactor
• A biochemically active enzyme results from the combination of an apoenzyme and cofactor
• A holoenzyme is a biochemically active conjugated enzyme

Enzyme Nomenclature and Classification

• Enzymes typically use a naming system providing functional information
• The nomenclature focuses on the reaction type and substrate identity
• The substrate is the enzyme-catalyzed reaction reactant
• The suffix "-ase" identifies a substance as an enzyme
• Some early-studied digestive enzymes still have names with the "-in" suffix
• Prefixes denote the type of reaction catalyzed
• "oxidase" indicates an oxidation reaction, while "hydrolase" indicates a hydrolysis reaction
• The substrate's identity is often added to the type of reaction, such as in glucose oxidase

Six Major Enzyme Classes

• Enzymes are classified based on the reactions they catalyze:
• Oxidoreductase catalyzes oxidation-reduction reactions.
• These require a coenzyme to be oxidized or reduced with the substrate.
• Lactate dehydrogenase removes hydrogen atoms as an oxidoreductase
• Transferase transfers functional groups between molecules
• Transaminases catalyze amino group transfers
• Kinases catalyze phosphate group transfers from ATP
• This yields ADP and a phosphorylated product
• Hydrolase catalyze hydrolysis reactions using water to break bonds
• Carbohydrases break glycosidic bonds
• Proteases break peptide linkages in proteins
• Lipases break ester linkages in triacylglycerols
• Lyase adds groups to double bonds or forms double bonds without hydrolysis or oxidation
• Dehydratase removes water components to form a double bond
• Hydratase adds water to a double bond
• Isomerase catalyzes the rearrangement of atoms within a molecule
• This converts the substrate into an isomeric form of itself
• There is only one reactant and product in isomerization
• Ligase joins two molecules into one, using ATP to participate

Models of Enzyme Action

• Enzymes act through an active site, a small portion where interaction occurs
• The active site is a 3D entity from different protein chain parts
• An enzyme-substrate complex is an intermediate formed when a substrate binds to the enzyme's active site

Lock-and-Key Model

• Lock-and-Key entails a fixed, rigid geometrical conformation at the enzyme's active site
• Only substrates with complementary geometry can be accommodated, common for numerous enzymes

Induced-Fit Model

• Induced-Fit incorporates flexibility in the enzyme's shape
• This allows small active site changes to accommodate the substrate
• Electrostatic interactions, hydrogen bonds, and hydrophobic interactions attract and bind substrate molecules

Enzyme Specificity

• Absolute Specificity: an enzyme acts on only one substrate, uncommon
• For example, Urease
• Stereochemical specificity involves distinguishing between stereoisomers
• L-amino-acid oxidase acts on L-amino acids but not D-amino acids
• Group specificity involves similar compounds with the same functional groups
• For example, Carboxypeptidase cleaves amino acids from the carboxyl end of the peptide chain
• Linkage specificity acts on a particular bond type
• Regardless of the structural features, phosphatases hydrolyze phosphate-ester bonds

Factors Affecting Enzyme Activity

• Temperature: reaction rate increases with temperature, but denatures past a certain point
• pH: enzymes have a narrow optimal pH range or denaturation occurs
• Substrate Concentration: reaction rate increases until full saturation, then levels off
• Enzyme Concentration: reaction rate increases with concentration, assuming substrate is more abundant

Enzyme Inhibition

• Inhibitors reduce rates of enzyme-catalyzed reactions
• Enzyme inhibitors slow or stop enzyme catalytic function by binding to it
• There are three modes of inhibition:
• Reversible competitive, reversible noncompetitive, and irreversible

Reversible Competitive Inhibition

• It involves inhibitors resembling the substrate, competing for the enzyme's active site
• Binding is temporary, preventing substrate occupancy and blocking the reaction
• Weak interactions maintain the complex, which breaks, freeing the active site over time
• Substrate and inhibitor compete

Reversible Noncompetitive Inhibition

• The inhibitor binds to a site other than the active site, decreasing enzyme activity
• The substrate still occupies the active site, but an enzyme structure change prevents proper catalysis

Irreversible Inhibition

• It involves inhibitors forming strong covalent bonds to active site amino acid side-chains, inactivating the enzyme
• These inhibitors often do not have structures similar to the enzyme's normal substrate

Allosteric Enzymes

• These enzymes have multiple protein chains (quaternary structure) and two binding sites: substrate and regulator
• Regulators, substances binding at the regulatory sites, are either positive or negative
• Positive regulators increase enzyme activity, and negative regulators decrease it

Regulation of Enzyme Activity

• Feedback Control involves product-controlled activation/inhibition of the first reaction in a sequence
• Proteolytic Enzymes and Zymogens: inactive precursors require an enzyme-controlled reaction to remove parts of their structure
• The proteolytic enzyme is the active form of a zymogen Covalent Modification of Enzymes happens through the attachment/removal of a chemical group to/from particular amino acids