ANSWERS GUARANTEE A+
✔✔metabolism or biotransformation typically alters chemicals from
(lipophilic/hydrophilic) to (lipophilic/hydrophilic) - ✔✔lipophilic;hydrophilic
✔✔which one favours absorption across biological membranes: (lipophilic/hydrophilic) -
✔✔lipophilic
✔✔which one favours elimination in urine or bile: (lipophilic/hydrophilic) - ✔✔hydrophilic
✔✔metabolism byproducts are ___, metabolism increasing toxicity is ___, metabolism
decreasing toxicity is ___ - ✔✔metabolites; bioactivation; detoxification
✔✔enzyme induction (2 points) - ✔✔xenobiotics stimulate the synthesis of enzymes
involved in the metabolic process, adaptive and reversible response to xenobiotic
exposure
✔✔T or F: enzyme induction enables some xenobiotics to accelerate their own
biotransformation and elimination from the body - ✔✔true
✔✔four categories of enzyme systems, based on reaction they catalyze - ✔✔hydrolysis,
reduction, oxidation, conjugation
✔✔the ___ contains the largest and most diverse source of biotransforming enzymes -
✔✔liver
✔✔beyond the liver, where else are biotransforming enzymes largely found (5) -
✔✔skin, lung, nasal mucosa, eye, GI tract - note! they exist elsewhere as well, these
locations just have significant amounts
✔✔T or F: intestinal microflora play an important role in the biotransformation of certain
xenobiotics - ✔✔true
✔✔within liver cells and most other organs, metabolic enzymes are primarily located in
which organelles? (2 major ones, 3 minor ones) - ✔✔endoplasmic reticulum & soluble
fraction in cytoplasm; others include mitochondria, nuclei, lysosomes
✔✔phase I metabolic reactions (3) - ✔✔functionalization (oxidative, hydrolytic,
reductive)
✔✔purpose of phase I reactions - ✔✔chemical modifications that introduce or uncover
functional groups on xenobiotic to provide sites for phase II
, ✔✔does phase I always happen before phase II? - ✔✔no! they can happen in parallel,
or phase I can be skipped entirely
✔✔phase II metabolic reactions (6) - ✔✔glucuronidation, sulfation, acetylation,
methylation, amino acid conjugation, glutathione conjugation
✔✔purpose of phase II reactions (2 main points) - ✔✔synthetic reaction of xenobiotic
(or phase I xenobiotic metabolite) with an endogenous substance, introduces
polar/ionizable groups to enhance hydrophilicity and excretion
✔✔what phase frees functional groups for further bonding - ✔✔phase I
✔✔if phase I is slow and phase II is fast, in most cases there is (higher/lower) toxicity -
✔✔lower
✔✔if phase I is fast and phase II is slow, in most cases there is (higher/lower) toxicity -
✔✔higher
✔✔T or F: phase I metabolism of lipophiles is primarily comprised of oxidation reactions
- ✔✔true
✔✔phase I metabolic reactions are primarily catalyzed by which enzymes -
✔✔cytochrome P450 enzymes
✔✔functionalization - ✔✔creates a new functional side group on molecule
✔✔degradation - ✔✔creates pathway for xenobiotic excretion
✔✔are cytochrome P450s hemoproteins; are many of them inducible - ✔✔yes; yes
✔✔which class of enzymes is present in the highest amount in liver and small
intestines, mainly in the membranes of the smooth ER - ✔✔cytochrome P450s
✔✔why are cytochrome P450 enzymes so common in phase I reactions (2) - ✔✔they
have a mixed-function oxidase complex which is insoluble and embedded within a
phospholipid membrane, this system can oxidize a wide spectrum of lipophilic
substrates including endobiotics and xenobiotics
✔✔CYP450 enzymes can create oxidized metabolites, is this always the case? - ✔✔no!
although they tend to form oxidized metabolites, they can also create non-oxygenated
metabolites via unmasking reactions (de-)