ANSWERS GUARANTEE A+
✔✔explain the CYP enzyme naming conventions in terms of CYP2D6 - ✔✔in CYP
family 2, subfamily D, gene number 6
✔✔phase I metabolism of lipophiles involves what kind of reactions, which enzymes -
✔✔oxidation, degradation, catalyzed by CYP450
✔✔phase II metabolism of lipophiles involves what kind of reaction - ✔✔conjugation - to
make them more hydrophilic compounds to enable excretion via kidney or liver
✔✔describe the typical changes in lipophilicity during biotransformation in terms of log
Kow - ✔✔log Kow will decrease! because it's becoming more hydrophilic
✔✔can metabolism occur in non-hepatic tissues - ✔✔yes! it can happen in the bladder,
kidneys, intestines, lungs etc.
✔✔phase III metabolism - ✔✔active transport elimination, reactions are often coupled
with efflux pumps to pump metabolite out
✔✔explain how a pesticide like malathion can be selectively toxic to insects but not
mammals and birds - ✔✔insects rely on P450s to metabolize it and P450s have MFOs
which form a toxic metabolite (malaoxon) while mammals and birds rely more on
esterases which form an inactive metabolite, the pathway in mammals is not CYP450
dependent
✔✔CYP1A1: location, substrates, bioactivation, inducible? - ✔✔many tissues especially
lung; PAHs, arenes, compounds with 2+ benzene rings, aromatic steroids; often makes
aryl epoxides; yes it's inducible
✔✔CYP1A2: location, substrates, bioactivation, inducible? - ✔✔mainly liver; PAHs,
arenes, compounds with 2+ benzene rings, aromatic steroids; often makes aryl
epoxides; yes it's inducible
✔✔regioselectivity - ✔✔preferential formation of one constitutional isomer over another,
but
functional group can be inserted on different regions of parent compound
✔✔stereoselectivity - ✔✔preference for the formation of one stereoisomer, but
substituent group can be inserted above or below ring
✔✔what is formed when a large compound covalently bonds with DNA, impacting
structure and function - ✔✔a bulky adduct
, ✔✔CYP2E1: location, substrates, bioactivation, inducible? - ✔✔in hepatic and non-
hepatic tissues; mainly small aliphatic compounds; oxidizes small straight or branched
chain compounds and benzene to form reactive metabolites; yes, upregulated by small
aliphatic compounds
✔✔nucleophilic - ✔✔electron rich, ex. DNA
✔✔electrophilic - ✔✔electron seeking, ex. toxic metabolites which eventually bind to
DNA and form DNA adducts
✔✔CYP3A4: location, substrates, bioactivation, inducible? - ✔✔hepatocytes and
enterocytes; prefers ringed aliphatic and mono-aromatic compounds; oxidizes drugs
and steroid compounds; moderately inducibly by substrates but can also be inhibited by
some food constituents
✔✔aflatoxins - ✔✔carcinogens produced in fungus-infected grains and nut products,
can cause acute hepatotoxicity but chronic exposure leads to liver cancer
✔✔epoxides and epoxy hydrase (EH) relationship - ✔✔phase I metabolism often
produces epoxides as toxic reactive metabolites, EH transforms epoxides into diols
allowing for rapid detoxification
✔✔epoxides (4) - ✔✔toxic metabolites produced by phase I metabolism, possible
carcinogenic to many tissues and is very electrophilic, they cannot be conjugated until
the epoxide ring is broken by hydrolysis
✔✔epoxy hydrase - ✔✔essential enzyme, transforms epoxides to diols for rapid
detoxification, considered potential anti-cancer
✔✔amygdalin - ✔✔cyanogenic glycoside (sugar molecule coupled to functional group
by glycosidic bond that releases cyanide when cleaved), releases cyanide into GI tract
where it binds to cytochrome A to stop ATP prod + inhibits selenoenzymes, found in
cassava almonds, lima beans
✔✔laetrile - ✔✔purified form of amygdalin sold as a "cancer treatment" by a fake doctor,
was not effective whatsoever and was obviously toxic
✔✔in what organelle(s) does phase I metabolism occur - ✔✔SER
✔✔in what organelle(s) does phase II metabolism occur - ✔✔SER, mitochondria,
cytoplasm