Biotransformation of Xenobiotics Flashcards
Xenobiotic biotransformation is performed by multiple enzymes in multiple subcellular
locations. Where would one of these enzymes most likely NOT be located?
a. cytosol.
b. Golgi apparatus.
c. lysosome.
d. mitochondria.
e. microsome.
Correct Answer: b. Golgi apparatus
Explanation: Biotransformation enzymes are found in the cytosol, microsomes (ER fragments), mitochondria, and lysosomes. The Golgi apparatus is mainly involved in protein packaging and secretion, not metabolic transformation.
All of the following statements regarding hydrolysis, reduction, and oxidation
biotransformations are true EXCEPT:
a. The xenobiotic can be hydrolyzed.
b. The xenobiotic can be reduced.
c. There is a large increase in hydrophilicity.
d. The reactions introduce a functional group to the molecule.
e. The xenobiotic can be oxidized.
Correct Answer: c. There is a large increase in hydrophilicity.
Explanation: Oxidation, reduction, and hydrolysis (Phase I reactions) often introduce or expose polar functional groups, but they do not drastically increase hydrophilicity—this occurs more in Phase II.
a, b, d, e are true for Phase I.
Which of the following is often conjugated to xenobiotics during phase II
biotransformations?
a. alcohol group.
b. sulfhydryl group.
c. sulfate group.
d. aldehyde group.
e. carbonyl group.
Correct Answer: c. Sulfate group
Explanation: Sulfation is a common Phase II conjugation reaction. Alcohol, aldehyde, and carbonyl groups are functional groups on xenobiotics, not conjugates. Sulfhydryl groups are rarely added (they’re usually involved in the structure of glutathione itself).C
Which of the following is a true statement about the bio-transformation of ethanol?
a. Alcohol dehydrogenase is only present in the liver.
b. Ethanol is reduced to acetaldehyde by alcohol dehydrogenase.
c. Ethanol and hydrogen peroxide combine to form acetaldehyde with the aid of catalase.
d. In spite of its catalytic versatility, cytochrome P450 does not aid in ethanol oxidation.
e. Acetaldehyde is oxidized to acetic acid in the mitochondria by aldehyde dehydrogenase.
Correct Answer: e. Acetaldehyde is oxidized to acetic acid in the mitochondria by aldehyde dehydrogenase.
Explanation: Ethanol is metabolized by:
Alcohol dehydrogenase: ethanol → acetaldehyde
Aldehyde dehydrogenase (in mitochondria): acetaldehyde → acetic acid
The other options are false or misleading.
Which of the following enzymes is responsible for the bio-transformation and elimination of
serotonin?
a. cytochrome P450.
b. monoamine oxidase.
c. flavin monooxygenase.
d. xanthine oxidase.
e. paraoxonase.
Correct Answer: b. Monoamine oxidase
Explanation: Monoamine oxidase (MAO) deaminates and metabolizes serotonin and other monoamines in the brain and liver.
Which of the following reactions would likely NOT be catalyzed by cytochrome P450?
a. dehydrogenation.
b. oxidative group transfer.
c. epoxidation.
d. reductive dehalogenation.
e. ester cleavage.
E
Explanation:
Cytochrome P450 enzymes are a superfamily of heme-containing monooxygenases primarily involved in oxidative metabolism. Let’s walk through each option:
a. dehydrogenation – TRUE (P450 can do this)
Cytochrome P450 enzymes can catalyze dehydrogenation reactions, especially on alcohols and amines, converting them into aldehydes, ketones, or imines.
b. oxidative group transfer – TRUE
This is a classic P450 function, such as hydroxylation of alkanes to alcohols or N-/O-dealkylation.
c. epoxidation – TRUE
Cytochrome P450s are heavily involved in epoxidation reactions, particularly with alkenes forming arene oxides and epoxides.
d. reductive dehalogenation – TRUE (less common, but still possible)
While P450s mostly carry out oxidative reactions, under low oxygen or anaerobic conditions, some P450s can catalyze reductive reactions like dehalogenation.
e. ester cleavage – FALSE (NOT catalyzed by P450)
This is NOT a typical P450-catalyzed reaction. Ester hydrolysis is typically mediated by esterases or hydrolases, not by cytochrome P450.
All of the following statements regarding cytochrome P450 are true EXCEPT:
a. Poor metabolism or biotransformation of xenobiotics is often due to a genetic
deficiency in cytochrome P450.
b. Cytochrome P450 can be inhibited by both competitive and noncompetitive inhibitors.
c. Certain cytochrome P450 enzymes can be induced by one’s diet.
d. Increased activity of cytochrome P450 always slows the rate of xenobiotic activation.
e. Induction of cytochrome P450 can lead to increased drug tolerance.
Correct Answer: d. Increased activity of cytochrome P450 always slows the rate of xenobiotic activation.
Explanation: Increased CYP450 activity can actually increase the rate of activation of pro-toxicants, sometimes making them more harmful.
a, b, c, and e are all true statements.
Which of the following statements regarding phase II bio-transformation (conjugation)
reactions is true?
a. Phase II reactions greatly increase the hydrophilicity of the xenobiotic.
b. Phase II reactions are usually the rate-determining step in the biotransformation and
excretion of xenobiotics.
c. Carboxyl groups are very common additions of phase II reactions.
d. Most phase II reactions occur spontaneously.
e. Increased phase II reactions result in increased xenobiotic storage in adipocytes.
Correct Answer: a. Phase II reactions greatly increase the hydrophilicity of the xenobiotic.
Explanation: The purpose of Phase II conjugation (e.g., glucuronidation, sulfation) is to increase solubility for excretion.
b is incorrect; Phase I is usually rate-limiting.
c is false; carboxyl groups aren’t commonly added.
d is false; these reactions are enzyme-catalyzed.
e is incorrect; there is no link to xenobiotic storage in adipose.A
Where do most phase II biotransformations take place?
a. mitochondria.
b. ER.
c. blood.
d. nucleus.
e. cytoplasm.
Correct Answer: e. Cytoplasm
Explanation: Many Phase II enzymes (e.g., transferases like UGT, SULT) are cytoplasmic, although some are microsomal.
ER (b) is also relevant but not the most correct general location.
Mitochondria, nucleus, and blood are incorrect.
Which of the following is not an important cosubstrate for phase II biotransformation
reactions?
a. UDP-glucuronic acid.
b. 3′-phosphoadenosine-5′-phosphosulfate (PAPS).
c. S-adenosylmethionine (SAM).
d. N-nitrosodiethylamine.
e. acetyl CoA.
Correct Answer: d. N-nitrosodiethylamine
Explanation: N-nitrosodiethylamine is a carcinogenic xenobiotic, not a cosubstrate.
Correct Phase II cosubstrates include:
UDP-glucuronic acid (for glucuronidation)
PAPS (for sulfation)
SAM (for methylation)
Acetyl CoA (for acetylation)
