Lecture 6 Flashcards
What is a Phase 1 Reaction?
it introduces a polar functional group into the xenobiotic (foreign) molecule
-OH, -COOH, -NH2, -SH
Which enzyme does most of the Phase 1 reactions?
CYP450
Heme molecules allows what?
It allows the oxygen to come in and oxidize our drug
_________ convert the relatively lipid-soluble xenobiotics to water-soluble (hydrophilic) compounds that can be excreted
Metabolic Reactions
Metabolism leads to compounds that are generally what?
Pharmacologically less active and relatively nontoxic
(also regarded as the detoxification process)
what is a prodrug?
Administers an inactive form of the drug and becomes active when it enters the body
what is the main purpose of phase 1 rxn?
to introduce a polar functional group into the xenobiotic molecule (-OH, -COOH, _NH2, -SH)
What type of reactions are considered phase 1?
-oxidations
-reductions
-hydrolysis
Aromatic Methyl Oxidation
Dehydration
4 types of Privileged positions
-Adjacent to a heteroatom-containing functional groups (S,O,N)
-Benzylic position
-Allylic Position
-Highly Substituted- C-H bonds (so a carbon with 3 R groups and a hydrogen)
Oxidative Dealkylation
you basically lose and akyl group (-CH3) and it attaches a hydrogen
Works on Primary, secondary, and Tertiary Groups
For Oxidative Dealkylation there are two different metabolic pathways
Oxidation & Dealkylation
Deamination
Only works on Primary and Secondary Amines
Converts the amine to either a ketone or aldehyde
N-Oxidation
N-oxidation transforms a basic amino group into a neutral motif, so a neutral group is not ionizable
this is a tertiary amine, so N-oxide
O & S dealkylations occurs in similar fashion to N dealkylations
What are Phase 2 (Conjugation) reactions?
typically attaches the polar and ionizable groups to the phase 1 metabolites or the xenobiotics containing the necessary polar functional groups to form water-soluble conjugated products devoid of activity
Phase 2: The Glutathione conjugation
Main purpose is to protect the body against the chemically reactive metabolites/xenobiotics
ex: acetaminophen
Phase 2: Acetylation
does not increase water solubility significantly
Phase 2: Methylation
does not lead to polar/water soluble metabolites except when a quaternary ammonium derivative is formed
