Enzymes: Function and Classification

Enzymes

• Enzymes are protein catalysts
• They speed up chemical reactions in living organisms
• Enzymes are crucial for life processes
• James B. Sumner isolated and crystallized enzymes in 1926
• All proteins?
• High molecular weight (MW)
• Catalysts (FAST AND FURIOUS)
• Active outside cells
• Water-soluble, amphoteric molecules
• Specificity

Enzyme Action

• Molecules must collide to react
• Collisions must have sufficient kinetic energy to break chemical bonds (activation energy)
• Higher temperatures increase molecular movement and the likelihood of collisions and bond breakage
• Enzymes lower activation energy needed for reactions to proceed
• Enzymes speed up reactions by binding to substrates in the active site
• The active site is specific to a particular substrate

Enzyme Classes

• Oxidoreductases: oxidation-reduction reactions (e.g., cytochrome oxidase, lactate dehydrogenase)
• Transferases: transfer functional groups (e.g., acetate kinase, alanine deaminase)
• Hydrolases: hydrolysis (addition of water) (e.g., lipase, sucrase)
• Lyases: removal of groups of atoms without hydrolysis (e.g., oxalate decarboxylase, isocitrate lyase)
• Isomerases: rearrangement of atoms within a molecule (e.g., glucose-phosphate isomerase, alanine racemase)
• Ligases: joining of two molecules using energy from ATP (e.g., acetyl CoA synthetase, DNA ligase)

Enzyme Activity

• Temperature: optimal temperature for human enzymes is 37°C; most enzymes denature at 70°C
• pH: optimal pH values vary; pepsin (pH 2) and trypsin (near pH 9). Extreme pH values cause denaturation.

Enzyme Inhibitors

• Irreversible inhibitors: permanently bind to the active site (e.g., nerve gases, pesticides)
• Reversible inhibitors: bind temporarily; competitive (compete with substrates) and non-competitive inhibitors.
• Noncompetitive inhibitors: bind to a different site affecting enzyme-substrate binding while not interfering with the substrate.

Cofactors and Coenzymes

• Cofactors: non-protein enzyme helpers (inorganic, organic)
• Coenzymes: organic cofactors (often vitamins)
  • Examples: NAD, FAD, CoA, thiamine pyrophosphate, flavin mononucleotide
• Coenzymes often aid in electron or functional group transfer
• Metal ions also behave as enzyme cofactors

Holoenzymes and Apoenzymes

• Holoenzyme: active enzyme with non-protein component
• Apoenzyme: inactive enzyme without non-protein component
• Cofactors could be metal ions or small organic molecules (coenzymes)

Enzyme Regulation

• Allosteric activation/inhibition: modulator molecules regulate enzyme activity by binding to allosteric sites (modulator site)
• Feedback inhibition: end product of a metabolic pathway shuts down the pathway
• Example: isoleucine synthesis

Zymogens

• Zymogens (pro-enzymes): inactive enzyme forms that need a specific event for activation
• Cleavage of a proteolytic chain is needed to activate the enzymes, it is irreversible
• Example: trypsin, chymotrypsin

Enzyme Localization

• Enzymes are often located in specific parts of cells
• Compartmentalization of enzymes increases efficiency
• E.g., mitochondria contain enzymes for cellular respiration

Additional Notes

• Vmax = maximum rate of reaction
• Km = affinity of an enzyme to substrate (where velocity is half Vmax)