Enzyme Classification

Enzyme Classification

Enzymes are biological catalysts — proteins (mostly) that accelerate chemical reactions by lowering the activation energy without being consumed. They are highly specific (substrate specificity, reaction specificity, stereospecificity) and regulated.

IUBMB Classification (6 Major Classes)

  • 1. Oxidoreductases: Catalyze oxidation-reduction reactions. Transfer of electrons (H or O). Key examples: Lactate dehydrogenase (LDH), Glucose-6-phosphate dehydrogenase (G6PD), Cytochrome oxidase. Coenzymes: NAD+, NADP+, FAD.
  • 2. Transferases: Transfer functional groups (methyl, phosphate, amino, acyl) from donor to acceptor. Examples: Aminotransferases (ALT, AST — used in LFTs), Hexokinase, Kinases (phosphate transfer). Coenzyme: PLP for aminotransferases.
  • 3. Hydrolases: Cleave bonds using water (hydrolysis). Digestive enzymes — Proteases (pepsin, trypsin, chymotrypsin), Lipases (pancreatic lipase), Amylase, Nucleases. Also ATPases, Phosphatases.
  • 4. Lyases: Cleave bonds WITHOUT water or oxidation; can form double bonds or rings. Examples: Pyruvate decarboxylase, Aldolase (cleaves fructose-1,6-bisphosphate), Carbonic anhydrase (adds CO₂ to water).
  • 5. Isomerases: Interconvert structural isomers/stereoisomers. Examples: Phosphoglucose isomerase (glycolysis), Triose phosphate isomerase, Epimerases, Mutases. No coenzyme required usually.
  • 6. Ligases (Synthetases): Join two molecules using energy from ATP hydrolysis. Examples: DNA Ligase, Pyruvate carboxylase, Acetyl-CoA Carboxylase, Aminoacyl-tRNA Synthetases.

Nomenclature System

Each enzyme is assigned a 4-number EC number: EC [class].[subclass].[sub-subclass].[serial number]. Example: Lactate dehydrogenase = EC 1.1.1.27 (class 1 = oxidoreductase; acts on CH-OH groups; NAD+ as acceptor).

Enzyme Specificity

  • Absolute specificity: Acts on only one substrate (Urease → urea only)
  • Group specificity: Acts on substrates with a particular group (Hexokinase → phosphorylates any hexose)
  • Bond specificity: Acts on a particular type of bond (any peptide bond → protease)
  • Stereospecificity: Distinguishes between optical isomers (L-amino acid oxidase acts only on L-forms)

Cofactors and Coenzymes

Apoenzyme (protein part) + Cofactor = Holoenzyme (active form). Cofactors may be: Metal ions (Mg²⁺ in kinases, Zn²⁺ in carbonic anhydrase, Fe²⁺ in catalase), or Coenzymes (organic, often derived from vitamins — NAD+, FAD, CoA, PLP).

Clinical Applications

  • Serum enzyme levels indicate organ damage (enzyme leak from damaged cells)
  • Enzyme replacement therapy (Gaucher's disease — recombinant glucocerebrosidase)
  • Enzymes as drug targets (Statins inhibit HMG-CoA reductase; ACE inhibitors block angiotensin-converting enzyme)