Phase 1 biotransformation Flashcards
what is the main principle of biotransformation
conversion of compounds from lipophilic (non-polar) to hydrophilic (polar) followed by excretion in urine or bile
what are the three types of phase 1 reactions
- hydrolysis
- reduction
- oxication
what is hydrolysis reaction
exposes or introduces a functional group
what is reduction reaction
adds an OH, Nh2, Sh, COOH
what is an oxidation reaction
adds COO- to become water soluble
what is needed for phase 2 reaction to happen
the new functional group added to the molecule must be nucleophilic or electrophilic
what is the main liver form of carboxyesterases, what does it do
CES1
- hydrolyzes xenobiotics with small alcohol leaving groups
what is the main intestinal form of carboxylesterases
CES2
- hydrolyzes xenobiotics with large alcohol leaving groups
what are three examples of cholinesterase’s
- acetylcholinesterase
- AChE inhibitors as therapeutics
- Organophosphates
what moieties can a xenobiotic have that can be reduced in vivo
aldehyde, ketone, disulfide, sulfoxide, quinone
what happens in a carbonyl reduction
carbonyl moieties (R-CHO and R1-CO-R2) reduced by carbonyl reductase
what happens with aldehyde dehydrogenase
oxidation of xenobiotic aldehydes formed from alcohol and non-alcohol molecules
what inhibits acetaldehyde dehydrogenase
disulfiram (antabuse)
what does monoamine oxidase do? (MAOA, MAOB)
oxidative deamination of primary, secondary, and tertiary amines
what enzyme metabolizes serotonin and chatecholamines
monoamine oxisase
what do CYP enzymes transform acetaminophen into
NAPQI
what are three things that reduce CYP activity
- genetic mutations
- environmental factors line infection or inflammation
- a xenobiotic that inhibits or competes with CYP
what are four things that increase CYP activity
- gene duplication
- gene mutation in promoter region
- a xenobiotic that increases activity of existing CYP protein
- a xenobiotic that increases expression of a CYP
describe sex differences in xenobiotic metabolism
- large in some rodents, lower for humans
- idiosynchratic drug reactions are more frequent in females
explain the interplay between intraconazole and carbamazepine and CYP3A4
intraconazole: anti-fungal that inhibits CYP3A4
Carbamazepine: anti-convulsant that induces CYP3A4
