Non Cyp Phase 1 Flashcards
What enzymes cause oxidation reactions
Flavin linked monooxygenases (FMO)
Prostaglandin H synthase dependent co oxidation
Amine oxidase
Oxidoreductase
What enzymes cause hydrolysis
Esterases
Epoxide hydrolases
Where are FMOs found
ER
What do FMOs oxidise
Nucleophilic N, P or S centres
What does FMO require
NADPH, O2 and FAD prosthetic group
FMO reaction mechanism
- NADPH reduces FAD —> FADH2
- O2 binds NAPD+-FADH2 complex
- Forms FADH-OOH
- Reacts with nucleophile substrate
- One O is incorporated into substrate and the other into water
- H2O and NADP+ is released
How many isoforms of FMO is there
5 - show 50-55% identity with each other
Give 2 examples of FMO catalysed reactions
N-deacetyl ketaconozole —> N-deacetyl-N-hydroxyketaconozole
Tamoxifen —> Tamoxifen-N-oxide
Which FMO is found at high levels in the human liver
FMO3
Which FMO is found in the human kidney
FMO1
Which FMO is found in rat liver
FMO1
Which FMOs are found in rat kidney
FMO1 FMO3 FMO4
Explain the co-oxidation quality of PGHS
COX activity (arachidonic acid —> PGG2)
Peroxidase activity (PGG2 —> PGH2)
What is PGHS’s role in paracetamol overdose
High doses of paracetamol can be converted to the toxic N-acetylquinoneimime in the kidney
What do amine oxidases oxidise
Monoamine
Diamines
Polyamines