TOX 4000 Lecture 3: Lecture 3 TOX4000
13 Oct 2018
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Department
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Professor
Lecture 3: Phase 1 reactions Sept. 14
Biotransformation: conversion of compounds from lipophilic to hydrophilic then excretion in
urine or bile
Phase 1: hydrolysis, reduction, oxidation
o Expose or introduce functional group
o Becomes water soluble
Phase 2: conjugation
o New functional group must be nucleophilic or electrophilic
o Addition of new side group
Hydrolysis
Carboxylesterases
Carboxylic ester + H2O → alcohol + carboxylate
CES1
Major liver form, also in other tissues
Hydrolyzes xenobiotics with small alcohol
leaving groups (e.g. quinapril)
CES2
Major intestinal form, also in kidney and brain
Hydrolyzes xenobiotics with large alcohol
leaving groups (e.g. aspirin)
CES3
Brain, liver, colon
CES4A
Brain, lung, kidney
CES5A
Brain, lung, testes
Cholinesterases
Acetylcholinesterase (AChE)
o Brain and muscle (neuromuscular junction)
o Acts on acetylcholine
AChE inhibitors as therapeutics
e.g. rivastigmine, galantamine, donepezil
