Detoxification Pathways Practice Questions

Q: Trilene is degraded by:

Cytochrome P450 oxidation. ***Cytochrome P450 oxidation*** - **Trichloroethylene (Trilene)** was historically used as an inhalational anesthetic and industrial solvent - In humans, it undergoes **hepatic metabolism primarily through cytochrome P450 enzymes**, particularly **CYP2E1** - The oxidation pathway produces metabolites including **chloral hydrate, trichloroethanol, and trichloroacetic acid** - This is a classic example of **Phase I detoxification** involving oxidative biotransformation - The metabolites are then conjugated (Phase II) or excreted renally *Glutathione conjugation* - While some chlorinated compounds undergo glutathione conjugation as a Phase II reaction - For trichloroethylene, **oxidation by CYP450 is the primary metabolic pathway**, not direct glutathione conjugation - GSH conjugation may occur with some metabolites but is not the main degradation route *Direct renal excretion* - Trilene is **lipophilic** and requires hepatic metabolism before elimination - Direct renal excretion without biotransformation is **minimal** - Metabolites (after oxidation) are excreted via kidneys *Acetylation* - **Acetylation** is a Phase II conjugation reaction typically for compounds with **amino or sulfonamide groups** - Trichloroethylene lacks the appropriate functional groups for acetylation - This pathway is **not involved** in Trilene metabolism

Q: The cytochrome involved in monooxygenase-mediated detoxification of drugs is:

Cyt P 450. ***Cyt P 450*** - **Cytochrome P450 (CYP450)** enzymes are a superfamily of heme-containing monooxygenases primarily responsible for the **metabolism of xenobiotics**, including the detoxification of drugs. - They catalyze oxidation reactions, introducing a hydroxyl group to substrates, which typically increases their **hydrophilicity** and facilitates excretion. *Cytochrome c* - **Cytochrome c** is a component of the **electron transport chain** in mitochondria, primarily involved in cellular respiration and energy production. - It acts as an **electron carrier** between Complex III and Complex IV, not directly in drug detoxification. *Cytochrome b5* - **Cytochrome b5** participates in various metabolic reactions, including **fatty acid desaturation** and cholesterol biosynthesis, and can sometimes assist CYP450 enzymes. - However, it does not function as a primary monooxygenase for drug detoxification itself. *Cytochrome oxidase* - **Cytochrome oxidase** (Complex IV) is the terminal enzyme in the **electron transport chain**, responsible for the reduction of oxygen to water. - Its main role is in cellular respiration, and it is not directly involved in drug monooxygenation or detoxification.

Q: Which amino acid primarily conjugates with benzoic acid during its detoxification?

Glycine. ***Glycine*** - **Benzoic acid** is detoxified in the liver by conjugation with **glycine**, forming **hippuric acid**, which is then excreted in the urine. - This is a well-known Phase II detoxification reaction, enhancing the water solubility and elimination of the xenobiotic. *Alanine* - **Alanine** is involved in **gluconeogenesis** via the **glucose-alanine cycle** and protein synthesis. - It is not primarily involved in the conjugation of benzoic acid for detoxification. *Tyrosine* - **Tyrosine** is a precursor for **catecholamines**, thyroid hormones, and melanin. - It does not participate in the detoxification pathway of benzoic acid. *Leucine* - **Leucine** is a **branched-chain amino acid (BCAA)** essential for protein synthesis and muscle repair. - It has no known role in the conjugation or detoxification of benzoic acid.

Q: In liver, ethanol is converted to?

Acetaldehyde. ***Acetaldehyde*** - In the liver, **ethanol** is primarily metabolized by **alcohol dehydrogenase (ADH)** into **acetaldehyde**. - **Acetaldehyde** is a highly toxic compound responsible for many of the adverse effects associated with alcohol consumption. *Methanol* - **Methanol** is a different type of alcohol (wood alcohol) and is not a product of ethanol metabolism. - Methanol is metabolized to **formaldehyde** and then **formic acid**, which are highly toxic. *Lactate* - **Lactate** is a product of anaerobic glycolysis and is not directly formed from ethanol metabolism. - While heavy alcohol consumption can lead to **lactic acidosis**, lactate itself is not the immediate, direct conversion product of ethanol. *Citric acid* - **Citric acid** is a key intermediate in the **Krebs cycle (citric acid cycle)**, involved in aerobic respiration. - It is not a direct product of ethanol metabolism; rather, **acetyl-CoA** (derived from acetaldehyde metabolism) can enter the Krebs cycle.

Question 1

Trilene is degraded by:

Accepted Answer

Cytochrome P450 oxidation

Answer

Glutathione conjugation

Answer

Direct renal excretion

Answer

Acetylation

Question 2

Biological role of metallothioneins is to sequester harmful metal ions. These bind which of the following ions?

Accepted Answer

Cadmium (Cd++), Copper (Cu++), and Zinc (Zn++)

Answer

Iron (Fe+++), Manganese (Mn++), and Chromium (Cr++)

Answer

Aluminum (Al+++), Mercury (Hg++), and Nickel (Ni++)

Answer

Platinum (Pt++), Arsenic (As+++), and Lead (Pb++)

Question 3

The cytochrome involved in monooxygenase-mediated detoxification of drugs is:

Accepted Answer

Cyt P 450

Answer

Cytochrome b5

Answer

Cytochrome c

Answer

Cytochrome oxidase

Question 4

Which amino acid primarily conjugates with benzoic acid during its detoxification?

Accepted Answer

Glycine

Answer

Alanine

Answer

Tyrosine

Answer

Leucine

Question 5

In liver, ethanol is converted to?

Accepted Answer

Acetaldehyde

Answer

Methanol

Answer

Lactate

Answer

Citric acid

Detoxification Pathways — MCQs

Detoxification Pathways — MCQs

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