Glutathione-S-transferases and conjugation

• What is the main focus of Part 2 of the study material?

  Glutathione - S-transferase and conjugation
• What are the structures of glutathione composed of?

  • Glutamate
  • Cysteine
  • Glycine
• Why is glutathione important for cells?

  It maintains a reducing environment for proteins.
• Where is glutathione found in high concentrations?

  In the liver.
• What triggers oxidation in the context of glutathione?

  Oxidation occurs from electrophilic species.
• How does glutathione interact with electrophiles?

  Glutathione reacts with electrophiles.
• What is the name of the enzyme that facilitates the reaction of glutathione with electrophiles?

  Glutathione - S - transferase.
• What are the three diverse superfamilies of glutathione - S - transferase enzymes in humans?

  • Isocytolic
  • Mitochondrial
  • Lysosomal & microsomal
• Why are hydroxyl and minogeneous groups important in drug metabolism?

  They are imperative for drug metabolism.
• What do microsomal enzymes primarily metabolize?

  Arachidonic acid (eicosanoid).
• What is the role of glutathione in detoxification?

  Glutathione is used to detoxify electrophiles.
• What type of addition occurs with α,β-unsaturated double bonds in the context of glutathione reactions?

  Conjugate addition.
• What is required for conjugate addition to proceed?

  An electron-withdrawing group (usually C=O).
• What intermediate is formed during the conjugate addition reaction?

  An enolate intermediate.
• What type of addition does paracetamol metabolism involve?

  1,6-conjugate addition.
• What produces the reactive intermediate in paracetamol metabolism?

  The CYP450 enzyme followed by dehydrogenases.
• What is routinely pooled in the nature of glucuronide?

  Glucuronide pool.
• What occurs during the conversion of conjugates to mercapturates?

  • Processing occurs in the liver and kidneys.
  • Results in negatively charged mercapturates.
  • Pathway involves glutamyl and glycyl residues.
• What is the role of cysteine in the conversion of mercapturates?

  Cysteine is involved in the removal of glycyl and glutamyl residues.
• What forms of catabolic enzymes exist?

  Hetero and homo forms.
• How many autowerenow exist in humans?

  20.
• What does the expression of glutathione enzymes depend on?

  It varies widely based on specific conditions.
• What induces the expression of glutathione enzymes?

  Physiological conditions.
• What is the consequence of polymorphisms in glutathione enzymes?

  They lead to altered metabolic rates.
• How do polymorphisms affect cancer chemotherapy?

  They can alter the effectiveness of drugs that target nucleophiles.
• What do drugs often react with in cancer chemotherapy?

  DNA and other nucleophiles.
• What is the effect of polymorphisms on metabolic rates?

  They can lead to altered metabolic rates.