Phase 2 drug metabolism Flashcards
what is phase 2 biotranformation
synthesis rxn. in which the endogenous substance combines with functional group
*** 6 types of phase 2 biotransformation conjugations
- glucuronide
- sulfate
- glutathione
- acetyl group
- methyl group
- amino acids
what do all phase 2 enzymes require
co-substrates (co-factors)
substrate for glucuronidation
UDP-GA
substrate for sulfination
PAPS
substrate for acetylation
caetyl CoA
substrate for methylation
SAM
what is sequence of phase 1 and 2 rxns
2 often follows 1, but not always - some don’t require 1 or either
what is glucouronidation
addition of glucouronic acid
what is code of glucouronidation
UGT___
how is glucounonic acid attached
indirect pathway
what are gilberts and crigler-najjars?
gilberts - only 20% of UGT works - jaundice
CN - 0% works
what is sulfation
reaction of phenols to produce highy ionic and polar sufuric acid esters
code for sulfation
SULT
what is glucatione conjugation
adds glucatione
code for glucatione
GST
what is important substrate for GST
NAPQI
what is acetylation
masks an amine with a non-ionizable group, so less water soluble
what is acetylation code
NAT
what is metylation
addition of a methyl group to
what is AA conjucation (2)
- conjucation ocarboxylic acid
2. conj of aromatic groups
6 factos that affect biotranformaiton
- species
- genetics
- age
- sex and hormones
- disease states
- diet, environmnt
what role do genetics play in metabolism
leads to functionally slow or fast metabolizers
what is effect of age
- neonates often have immature enzymes - hyperbilirubinemia
2. old people have lower liver mass and blood flow
how does sex effect
not generall clincally relevant, but hormones can play a role - alc less metabolized by women
how does disease effect (3)
- liver disease
- CVD - less perfusion of liver
- thyroid issues can change metabolism
what does St. johns wort do?
induces enzyme (CYP3A4) that breaks down cyclosporine, which is an immunosuppresant
