Phase II Metabolism Flashcards
What is Phase II drug metabolism?
Phase II metabolism involves conjugation reactions that attach polar groups to Phase I metabolites, increasing their water solubility for easier excretion.
What are the main types of Phase II reactions?
The main Phase II reactions include glucuronidation, sulphation, amino acid conjugation, glutathione conjugation, acetylation, and methylation.
What is glucuronidation?
Glucuronidation involves transferring a glucuronyl group to a substrate, making it more polar and excretable. It is catalyzed by UDP-glucuronosyl transferase (UGT) using UDP-glucuronic acid (UDPGA) as a donor molecule.
What are examples of glucuronidation?
Salicylic acid undergoes O-glucuronidation to form salicyl phenolic glucuronide, and sulphanilamide undergoes N-glucuronidation to form sulphanilamide glucuronide.
What functional groups are targeted in glucuronidation?
Functional groups include hydroxyl (-OH), carboxyl (-COOH), amino (-NH2), and thiol (-SH) groups.
What is sulphation?
Sulphation involves transferring a sulphate group to a substrate, catalyzed by sulfotransferase using 3’-phosphoadenosine-5’-phosphosulfate (PAPS) as a donor molecule.
What are examples of sulphation?
Paracetamol undergoes sulphation to form paracetamol sulphate.
What functional groups are targeted in sulphation?
Functional groups include hydroxyl (-OH), amino (-NH2), and phenolic groups.
What is amino acid conjugation?
Amino acid conjugation attaches amino acids, such as glycine or glutamine, to carboxylic acids in drugs. It is catalyzed by N-acyl transferase after activation of the drug to an acyl-CoA intermediate.
What are examples of amino acid conjugation?
Salicylic acid undergoes glycine conjugation to form salicyluric acid.
What functional groups are targeted in amino acid conjugation?
Carboxylic acids (-COOH) are the primary targets.
What is glutathione conjugation?
Glutathione conjugation attaches a tripeptide (glu-cys-gly) to reactive electrophilic substrates. It is catalyzed by glutathione S-transferase (GST).
What are examples of glutathione conjugation?
N-acetyl-p-benzoquinoneimine (NAPQI), a toxic paracetamol metabolite, is conjugated with glutathione to form a glutathione conjugate.
What functional groups are targeted in glutathione conjugation?
Electrophilic groups like epoxides, quinones, and halides are targeted.
What is acetylation?
Acetylation involves transferring an acetyl group to a substrate, catalyzed by N-acetyl transferase (NAT) using acetyl-CoA as a donor.
What are examples of acetylation?
Sulphanilamide is acetylated to form N-acetyl sulphanilamide.
What functional groups are targeted in acetylation?
Amino (-NH2) and hydroxyl (-OH) groups are common targets.
What is methylation?
Methylation involves adding a methyl group to a substrate, catalyzed by methyltransferases using S-adenosyl methionine (SAM) as a donor.
What are examples of methylation?
L-DOPA undergoes O-methylation by catechol-O-methyltransferase (COMT) to form methyl-L-DOPA. 6-mercaptopurine undergoes S-methylation by thiopurine S-methyltransferase (TPMT) to form methyl-6-mercaptopurine.
What functional groups are targeted in methylation?
Common targets include phenolic (-OH), catecholic, amino (-NH2), and thiol (-SH) groups.
What is the significance of glucuronidation and sulphation interplay?
Glucuronidation and sulphation are competing pathways. Sulphation predominates at low substrate concentrations, while glucuronidation predominates at higher concentrations due to limited PAPS availability.
What is the clinical relevance of Phase II metabolism?
Phase II metabolism reduces the pharmacological activity and toxicity of drugs, aiding in their elimination. Exceptions include acetylation and methylation, which may mask polar groups, reducing water solubility.
