Enzyme Induction and Repression

Enzyme Synthesis Control - Regulating the Enzyme Factory

• Cells precisely control enzyme concentrations by modulating their synthesis (gene expression) or degradation rates, crucial for metabolic adaptation.
• Follows Central Dogma: $DNA \rightarrow mRNA \rightarrow Protein (Enzyme)$.
• Key Regulation Levels:
  • Enzyme Quantity Control: Regulates total enzyme amount. Involves altering gene expression (induction/repression). Slower, long-term response.
  • Enzyme Activity Control: Modifies function of pre-existing enzymes (e.g., allosteric, covalent). Faster, immediate response.

⭐ Regulation of enzyme quantity (induction/repression) is a slower, long-term adaptive response compared to allosteric regulation of enzyme activity.

Enzyme Induction - Crank Up the Volume!

• Definition: ↑ synthesis of enzyme protein due to an inducer.
• Mechanism:
  • Inducer (substrate, drug, hormone) binds regulatory protein (activator/de-repressor).
  • Alters protein conformation, ↑ gene transcription (mRNA synthesis).
  • Results in ↑ enzyme synthesis.
• Examples:
  • Lac Operon (E. coli): Lactose (inducer) → ↑ β-galactosidase.
  • CYP450 Enzymes: Drug-induced; affects drug metabolism.
    • 📌 Phenytoin, Rifampicin, Alcohol (chronic), Carbamazepine, St. John's Wort, Griseofulvin, Phenobarbital Smoke (tobacco) induce CYP enzymes. (CRAPS GPS + Smoke)

⭐ Rifampicin, a potent inducer of CYP3A4, can lead to therapeutic failure of drugs like oral contraceptives and warfarin.

Enzyme Repression - Mute the Messengers!

• Definition: ↓ enzyme synthesis rate due to a signal, typically the pathway's end-product (feedback repression). Primarily affects anabolic enzymes.
• Mechanism:
  • Corepressor: Signal molecule (e.g., end-product) binding the aporepressor.
  • Aporepressor: Inactive repressor protein; activated by corepressor.
  • Corepressor + Aporepressor → Active Repressor Complex.
  • Active repressor binds to the operator gene on DNA.
  • Blocks RNA polymerase → ↓ mRNA transcription → ↓ enzyme synthesis.

• Key Examples:
  • Tryptophan (Trp) Operon: Tryptophan is the corepressor.

    ⭐ In the Tryptophan operon, tryptophan itself acts as a corepressor, leading to feedback inhibition of its own synthesis pathway.

  • Heme Synthesis: Heme (end-product) represses ALA synthase (δ-aminolevulinate synthase), its pathway's rate-limiting enzyme.

Clinical Correlates - Doctor's Dilemma: Enzyme Flux

• Induction: ↑ enzyme (e.g., CYP450) synthesis by drugs → accelerated metabolism.
  • Impact: ↓ drug efficacy, ↑ toxic metabolites, interactions.
  • Therapeutic use: Phenobarbital: Crigler-Najjar II, neonatal jaundice (induces UGT).
• Repression: ↓ enzyme synthesis → ↓ metabolism.
  • Impact: ↑ drug toxicity, ↓ active drug formation.
• Faulty Regulation: Faulty induction/repression (genetics, disease) → metabolic disorders.

Key Drug Inducers & Clinical Impact

High‑Yield Points - ⚡ Biggest Takeaways

Error: Failed to generate content for this concept group.