L3 (NATs) Flashcards
True or false ?
Acetylation of Xenobiotic Substrates by NAT Enzymes.
Cytosolic NATs utilize the cofactor acetyl coenzyme A to acetylate drugs and xenobiotics that contain amino and hydrazine substituents to the
corresponding amides and hydrazides, respectively.
True ✅
True or false?
There are two NATs: NAT1 and NAT2; that mediate not only the N-acetylation but also the O-acetylation of suitable substrates.
True ✅
True or false?
NAT1 is widely expressed in most human tissues. NAT2 exhibits a more restricted distribution in liver, small intestine, and colon.
True ✅
True or false ?
The active center of NAT1 is smaller than that of NAT2, which suggests that a more limited range of substrates is accommodated by the enzyme
True ✅
Complete:
Substrates of NAT1 include….
1/ p-amino benzoic acid,
2/p-amino salicylic acid,
3/the folate metabolite p-amino benzoyl glutamate.
Complete:
A wide range of drug substrates for NAT2 has been described, including:
1/sulfamethazine,
2/procainamide,
3/dapsone,
4/ isoniazid,
5/many xenobiotic arylamines.
True or false ?
The “acetylation polymorphism” is probably the best established example of a genetic defect in drug biotransformation that precipitates drug toxicity. This polymorphism was initially recognized in tuberculous patients who received the hydrazine drug (isoniazid) that is eliminated principally by
acetylation.
True ✅
True or false ?
“Rapid acetylators” were competent in isoniazid acetylation, whereas the
“slow acetylators” cleared drug slowly, which led to its accumulation in
serum.
True ✅
True or false ?
Decreased rates of isoniazid acetylation in slow metabolizers promoted
the formation of neurotoxic metabolites .
True ✅
True or false ?
The incidence of systemic lupus erythematosus is increased in slow
acetylators who received hydralazine or procainamide.
True ✅
True or false ?
Hemolytic anemia and inflammatory bowel disease were more frequent in
slow acetylators who received sulfasalazine.
True ✅
True or false?
Hepatotoxicity is increased in slow acetylators.
True ✅
