ADME 7 Flashcards
what is Phase I Metabolism Functionalization?
Introduction of polar functional groups into molecules- usually by addition of oxygen
what does phase 1 metabolism functionalization require?
Require NADH or NADPH (electron source) and O2as cofactors
•NADPH-P450 reductase(or cytochrome b5) enzyme used as electron carrier
where are Mixed function oxidases or monooxygenase located?
liver- in the endoplasmic reticulum
where does oxidation most dominantly occur in aromatic rings?
in electron rich system- OH usually introduced in para position
what prevents or slows oxidation?
electron withdrawing groups (e.g. Cl, N+R3, COOH, SO2NHR) slow or prevent oxidation
what is Benzo[a]pyrene?
Polycyclic aromatics –common constituents of soot, tars, car exhausts, burnt foods–Benzo[a]pyrene
–the first isolated carcinogen
what are the oxidation of alcohols and aldehydes catalyzed by?
Catalysed by non-microsomal dehydrogenases–alcohol dehydrogenase
–aldehyde dehydrogenase
what is a benzylic carbon?
benzne ring with a carbon directly attached
if you oxadize a primary methyl benzylic what do you get?
primary alcohol
what is an allylic carbon?
C adjacent to a C=C
what is a saturated carbon?
Occurs in drugs with straight or branched alkyl chains
where does oxidation occur in a saturated carbon?
Oxidation at terminal methyl groups –“omega” (w)
•Oxidation at the next to the last carbon –“omega –1” (w-1)
inserts a hydroxyl
what happens in the oxidation of a carbon to a heteroatom?
Oxidation of carbon attached to O, S, N
–also termed N-, O-,S-dealkylation
–note initial oxidation of C-H followed by elimination
what are secondary amines subject to?
Secondary amines subject to N-dealkylations, oxidative deamination, and N-oxidations
•N-dealkylation proceeds similar to tertiary amines
what does Insertion of oxygen into an N-H bond leads to?
N-oxidation
