28 Questions
What plays a crucial role in the formation of GSH conjugates of electrophilic xenobiotics or metabolites?
GSH S-transferases
What is the product of the conjugation reaction between GSH and electrophilic xenobiotics or metabolites?
Mercapturic acids
What type of xenobiotics or metabolites undergo conjugation with GSH?
Electrophilic
What is the role of GSH S-transferases in the conjugation reaction?
To catalyze the conjugation of GSH with electrophilic xenobiotics or metabolites
What is the result of the conversion of GSH conjugates of electrophilic xenobiotics or metabolites?
Formation of mercapturic acids
Which of the following compounds is not a primary amino group, but can still undergo acetylation?
Quaternary ammonium compounds
What is the functional group that undergoes acetylation in primary aromatic amines?
ArNH2
Which of the following statements is true about the acetylation of hydrazines?
It is a specific reaction to primary amino groups
What is the general term for the functional group that undergoes acetylation in sulfonamides?
Primary amino group
Which of the following compounds can undergo acetylation due to the presence of a primary amino group?
Aniline
What is the primary functional group that undergoes sulfation in sulfate conjugation?
Phenols
Which of the following compounds is NOT a common substrate for sulfation?
Glucose
What is the primary step in the sulfate conjugation process?
Activation of inorganic sulfate to PAPS
Which of the following is the order of preference for sulfation?
Phenols > Alcohols > Aromatic amines > N-hydroxyl
Which of the following is a characteristic of sulfate conjugation?
It is a less frequent conjugation method than glucuronidation
What is the role of PAPS in sulfate conjugation?
It is the activated form of inorganic sulfate
What is the result of the process involving γ-glutamylcysteine}
Formation of S-substituted cysteine residue
What is the product of the reaction involving glutathione?
Glutathione adduct
What is the outcome of the enzymatic cleavage of two amino acids?
Removal of glutamic acid and glycine
What is the purpose of N-acetylation in this process?
To stabilize the S-substituted cysteine residue
What is the intermediate formed in the process involving γ-glutamylcysteine?
Glutathione adduct
What is the final product of the process involving γ-glutamylcysteine?
N-acetylated S-substituted cysteine residue
What is the result of regioselective O-demethylation of the 4-OCH3 group in papaverine?
Formation of an alcohol
What has changed significantly in recent years regarding drug metabolites?
The traditional idea of drug metabolites being inactive
What is the current understanding of pharmacologically active metabolites?
They are sometimes active and significant
What is the name of the process by which the 4-OCH3 group in papaverine is converted to an alcohol?
Regioselective O-demethylation
What is the significance of pharmacologically active metabolites in drug therapy?
They are sometimes a desired outcome of drug treatment
What is the implication of increasing evidence on pharmacologically active metabolites?
Drug metabolites are sometimes active and significant
Study Notes
Sulfate Conjugation
- Sulfate conjugation (sulfation) is less frequent compared to glucuronide conjugation (glucuronidation)
- The most common functional groups that undergo sulfation are free OH, NH2, and NHOH
- Phenols (Ph-OH) are the main group of substrates that undergo sulfate conjugation, followed by:
- Alcohols (ROH)
- Aromatic amines (ph-NH)
- N-hydroxyl (N-OH)
Substrates of Sulfate Conjugation
- Sulfation is used to conjugate endogenous compounds, including:
- Steroids
- Heparin
- Chondroitin
- Catecholamines
- Thyroxine
Sulfate Conjugation Process
- The process involves the activation of inorganic sulfate (SO4) to form CoEnzyme 3′-phosphoadenosine-5′-phosphosulfate (PAPS)
GSH Conjugation
- Formation of GSH conjugates of electrophilic xenobiotics or metabolites (E) occurs through enzymatic cleavage of two amino acids (glutamic acid and glycine) from the formed GSH adduct
- Subsequent N-acetylation of the remaining S-substituted cysteine residue forms mercapturic acids
- Conjugation of substrates with GSH is catalyzed by enzymes known as GSH S-transferases
Acetylation
- The functional group undergoing acetylation is the primary amino group (NH2), including:
- Primary aromatic amines (ArNH2)
- Sulfonamides (H2NC6H4SO2NHR)
- Hydrazines (-NHNH2)
Pharmacologically Active Metabolites
- The traditional idea that drug metabolites are inactive and insignificant in drug therapy has changed dramatically in recent years
- Evidence suggests that many drugs undergo biological transformation, leading to pharmacologically active metabolites
Learn about sulfate conjugation, a type of phase II biotransformation, its frequency, and the most common functional groups that undergo sulfation, including phenols and alcohols.
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