Biotransformation 1 Flashcards
what needs to happen for a compound to be excreted
it needs to be changed from lipophilic to hydrophilic
three reasons to get rid of lipophilic xenobiotics
narcotic effect
accumulation
toxic effects
two different kinds of substrates
endogenous
xenobiotics
four consequences of biotransformation
increase of hydrophilicity
change of biological activity
increase in molecular weight
activation of compound
three principles of biotransformation
enzymatic reactions
often broad substrate specificity
tissue specific expression
changes compounds from one form to another
biotransformation
process of generating energy from a food source
can be interchanged with biotransformation
metabolism
what is being formed during biotransformation
metabolites
phase one of biotransformation
introduce, expose a functional group through oxidation hydrolysis and reduction
adding a functional group doesn’t really _____
increase hydrophilicity
phase two of biotransformation
add hydrophilic group through conjugation reactions
reactive functional group added to compounds
epoxide groups
six characteristics for cytochrome p450 enzymes
very important group
large number of isoforms
mostly in liver, but found in other tissues
functions: biosynthesis, detoxification, activation
located on ER
all contain heme group at active site
two things always needed for basic CYP reaction
oxygen and energy
what is located by CYP and provides energy
NADPH cytochrome P450 reductase
families 1,2 and 3 CYP deal with
mostly xenobiotics
families 4 and up CYP deal with
mostly endogenous substrates
inducible, important for metabolism of aromatic hydrocarbons, activation of procarcinogens, EROD assay as specific substrate
CYP1A family
induction by phenobarbital
CYP2B
oxidation of ethanol, inducible, also uses acetaminophen
CYP2E1
high constitutive expression, inducible, very important, numerous substrates, inhibition by grapefruit juice
CYP3A4
how does inhibition of CYP happen
through drug-drug interactions
what can sometimes form from inhibition of CYP
ROS species
explain Ah receptor and CYP1A induction
ligand binding to receptor
changes the AhR conformation
AhR moves into the nucleus which binds with ARNT
binds to DNA at promoter
leads to transcription of mRNA
leads to production of proteins that run phase I and II
PCB’s that are _____bind to AhR
in the same plane
anther type of aromatic compound can also bind to AhR receptors and disrupt homeostasis
bromine compounds
alcohols get broken down into
acids
four characteristics of flavin monooxygenases
similar to CYPs but have a flavin group instead
need NADPH and oxygen to run
active at high pH range (8-10)
substrates can often be used by CYPs
types of substrates that flavin groups take
mostly secondary and tertiary N, S, and P groups
deficiency in FMO3 leads to
fish-odor syndrome, no breakdown of trimethylamine
other phase I enzymes that perform hydrolysis
esterases
epoxide hydrolase
other phase I enzymes that perform reduction
azo/nitro reduction
quinone reduction
reductive dehalogenation
