Xenobiotics: Sources

Question 1

What is a xenobiotic?

Answer 1

A xenobiotic is any foreign compound to the body, including toxins, drugs, food additives, and environmental pollutants.

Question 2

Name some sources of environmental pollutants.

Answer 2

1. Pesticides (e.g., DDT, parathion)
2. Industrial Chemicals (e.g., polychlorobiphenyls, methanol)
3. Air Pollutants (e.g., carbon monoxide, smog)
4. Food Toxins (e.g., cyanide in food, alkaloids in mushrooms)

Question 3

What is biotransformation?

Answer 3

Biotransformation is the chemical modification of substances in the body, often turning harmful substances into more water-soluble, less harmful forms, or sometimes more toxic forms (bioactivation).

Question 4

What happens in Phase I metabolism?

Answer 4

Phase I reactions involve oxidation, reduction, hydrolysis, or hydration to add functional groups (like –OH, –NH₂) for Phase II conjugation.

Question 5

What does the cytochrome P450 (CYP450) system do in Phase I?

Answer 5

CYP450 enzymes carry out oxidation reactions, adding oxygen to xenobiotics. This includes reactions like hydroxylation, epoxidation, and N-dealkylation.

Question 6

Give an example of a substrate for aromatic hydroxylation in Phase I metabolism.

Answer 6

Lignocaine (local anesthetic) undergoes aromatic hydroxylation.

Question 7

What is an example of aliphatic hydroxylation?

Answer 7

Pentobarbitone (barbiturate) undergoes aliphatic hydroxylation.

Question 8

What happens during Phase II metabolism?

Answer 8

Phase II involves conjugation, where an endogenous molecule (e.g., glucuronic acid, sulfate, acetate) is added to Phase I metabolites to make them more water-soluble and easier to excrete.

Question 9

What are the main enzymes involved in Phase II conjugation?

Answer 9

1. UDP-glucuronosyltransferase (for glucuronidation)
2. Sulfotransferase (for sulfation)
3. Methyltransferase (for methylation)
4. Acetyltransferase (for acetylation)
5. Glutathione-S-transferase (for glutathione conjugation)

Question 10

What enzyme and cofactor are involved in glucuronidation?

Answer 10

Enzyme: UDP-glucuronosyltransferase (UGT)

Cofactor: UDP-glucuronic acid

Question 11

What is the first step in the metabolism of naphthalene?

Answer 11

Phase I: Oxidation by cytochrome P450, forming a reactive intermediate.

Question 12

What happens in Phase II of naphthalene metabolism?

Answer 12

Glutathione attaches to the intermediate, forming a glutathione conjugate for excretion.

Question 13

How do species affect drug metabolism?

Answer 13

Different species metabolize drugs at different rates or by different pathways. For example, humans metabolize caffeine differently than monkeys or rats.

Question 14

How do genetic differences affect drug metabolism in humans?

Answer 14

Some people are fast acetylators (process drugs quickly), while others are slow acetylators. This can affect how drugs like isoniazid work in the body.

Question 15

How does grapefruit juice affect drug metabolism?

Answer 15

Grapefruit juice inhibits CYP3A4 enzymes, increasing drug bioavailability and possibly causing more adverse effects.

Question 16

What is bioactivation in xenobiotic metabolism?

Answer 16

Bioactivation is when a non-toxic compound is converted to a toxic metabolite during metabolism — often during Phase I.

Question 17

Give an example of a compound that becomes toxic through bioactivation.

Answer 17

Parathion is bioactivated to paraoxon (a potent acetylcholinesterase inhibitor).

Question 18

What is the role of glutathione in detoxification?

Answer 18

Glutathione (GSH) binds to toxic electrophilic metabolites, neutralizing them and making them safe for excretion.

Question 19

Which toxic compound is detoxified by glutathione?

Answer 19

The toxic intermediate NAPQI from paracetamol metabolism is detoxified by glutathione.

Question 20

What are microsomes in drug metabolism?

Answer 20

Microsomes are vesicles formed from the smooth endoplasmic reticulum; they contain CYP450 enzymes and are used in lab tests to study metabolism.

Question 21

Name 3 enzymes involved in xenobiotic metabolism that are non-microsomal.

Answer 21

1. Alcohol dehydrogenase
2. Aldehyde dehydrogenase
3. Monoamine oxidase (MAO)

Question 22

Give an example of oxidation not catalyzed by cytochrome P450.

Answer 22

Ethanol oxidation by alcohol dehydrogenase (not CYP450) → produces acetaldehyde.

Question 23

What happens in Phase I reduction reactions?

Answer 23

Oxygen is removed or hydrogen is added to a xenobiotic, usually under low oxygen (anaerobic) conditions.

Question 24

Give an example of a drug that undergoes reduction.

Answer 24

Chloral hydrate is reduced to trichloroethanol (its active form).

Question 25

What are the three main steps in naphthalene detoxification?

Answer 25

1. Oxidation (by CYP450) 2. Glutathione conjugation 3. Conversion to mercapturic acid (non-toxic, excreted in urine)

Question 26

What types of functional groups do Phase II enzymes act on?

Answer 26

–OH, –COOH, –NH₂, –SH, and other nucleophilic groups.

Question 27

Why can Phase I metabolism sometimes be dangerous?

Answer 27

It can form toxic reactive intermediates like epoxides, free radicals, or quinones.

Question 28

What is a conjugation reaction in metabolism?

Answer 28

It is when a body-made molecule (e.g., glucuronic acid, sulfate, glutathione) is attached to the xenobiotic, making it non-toxic and water-soluble.

Question 29

Give a drug that undergoes amino acid conjugation.

Answer 29

Salicylic acid (from aspirin) is conjugated with glycine.

Question 30

What is the purpose of fatty acid conjugation in metabolism?

Answer 30

It forms lipid-soluble metabolites (e.g., lipid amides), often to allow storage or delayed release in tissues.

Question 31

What is a condensation reaction in xenobiotic metabolism?

Answer 31

It is a Phase II reaction where a toxic intermediate reacts with a body molecule to form a stable, non-toxic product — not as common, and often overlaps with glutathione or amino acid pathways.

Question 32

Why is xenobiotic metabolism important for everyday Nigerians?

Answer 32

Because of exposure to pesticides, herbal mixtures (agbo), mothballs (naphthalene), smoke, drugs, and counterfeit products — knowing how the body handles toxins saves lives.