Cytochrome P450 Questions: Trivia Quiz!

1. What is the reaction scheme of P450?

DOH + NADPH + O2 --> DH + NADP + H20

DH + NADPH + O2 --> DOH + NADP + H2O

DH + NADP + H2O --> DOH + NADP + 02

The correct answer is DH + NADPH + O2 --> DOH + NADP + H2O. This reaction scheme shows the conversion of DH (a substrate) into DOH (a product) in the presence of NADPH and O2. The reaction also produces NADP and H2O as byproducts.

Explanation

The correct answer is DH + NADPH + O2 --> DOH + NADP + H2O. This reaction scheme shows the conversion of DH (a substrate) into DOH (a product) in the presence of NADPH and O2. The reaction also produces NADP and H2O as byproducts.

2. What are the main functions of P450?

Xenobiotic metabolism; steroid, fatty acid and vitamin reduction; steroid synthesis

Xenobiotic metabolism; steroid, fatty acid and vitamin oxidation; steroid biosynthesis

Xenobiotic metabolism; steroid, fatty acid and acetaldehyde oxidation; steroid biosynthesis

The main functions of P450 include xenobiotic metabolism, which involves the breakdown and elimination of foreign substances in the body, such as drugs and toxins. P450 also plays a role in the oxidation of steroids, fatty acids, and vitamins, which is important for various physiological processes. Additionally, P450 is involved in the biosynthesis of steroids, which are essential for various functions in the body.

Explanation

The main functions of P450 include xenobiotic metabolism, which involves the breakdown and elimination of foreign substances in the body, such as drugs and toxins. P450 also plays a role in the oxidation of steroids, fatty acids, and vitamins, which is important for various physiological processes. Additionally, P450 is involved in the biosynthesis of steroids, which are essential for various functions in the body.

3. Which of these statements best describes the properties of CYP3A4 substrates; and which are CYP3A4 substrates?

Large binding site allowing for considerable structural diversity in substrates, majority of binding involves ionic bonding; rifampicin, penicillin

Large binding site allowing for considerable structural diversity in substrates, majority of binding involving hydrophobic interactions; erythromycin, lidocaine, tamoxifen

Large binding site allowing for considerable structural diversity in substrates, majority of binding involves Hydrogen bonding; erythromycin, rifampicin

The correct answer states that CYP3A4 substrates have a large binding site that allows for a wide range of structural diversity in substrates. The majority of the binding between CYP3A4 and its substrates occurs through hydrophobic interactions. The specific substrates mentioned in the answer are erythromycin, lidocaine, and tamoxifen.

Explanation

The correct answer states that CYP3A4 substrates have a large binding site that allows for a wide range of structural diversity in substrates. The majority of the binding between CYP3A4 and its substrates occurs through hydrophobic interactions. The specific substrates mentioned in the answer are erythromycin, lidocaine, and tamoxifen.

4. Which P450 isoforms, in order, are resposible for imipramine metabolism?

CYP2D6, CYPA12, CYP3A4; CYP2C9

CYP2C19, CYP1A2, CYP3A4; CYP2D6

CYP2C9, CYPA12, CYP3A4; CYP2D6

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Explanation

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5. Which of these statements best describes the properties of CYP2D6 substrates; and which are CYP2D6 substrates?

The correct answer describes the properties of CYP2D6 substrates as having a basic nitrogen that is mainly ionized at physiological pH and a hydrophobic region. These substrates undergo oxidation usually 5-7 A from the basic nitrogen. The examples given, such as propanolol, debrisoquine, amitriptyline, and clozapine, are mostly cardiovascular and psychoactive agents.

Explanation

The correct answer describes the properties of CYP2D6 substrates as having a basic nitrogen that is mainly ionized at physiological pH and a hydrophobic region. These substrates undergo oxidation usually 5-7 A from the basic nitrogen. The examples given, such as propanolol, debrisoquine, amitriptyline, and clozapine, are mostly cardiovascular and psychoactive agents.

6. Which of these statements best describes the properties of CYP2C9 substrates; and which are CYP2C9 substrates?

The correct answer states that CYP2C9 substrates have areas of strong H bond/ion forming potential 5 - 10 A from the site of metabolism. These substrates mainly include NSAIDs (nonsteroidal anti-inflammatory drugs) such as ibuprofen, as well as S-warfarin, tolbutamide, and paracetamol. This means that these drugs have the ability to form strong hydrogen bonds or ionic interactions within a specific distance from the site of metabolism, which is important for their interaction with the CYP2C9 enzyme.

Explanation

The correct answer states that CYP2C9 substrates have areas of strong H bond/ion forming potential 5 - 10 A from the site of metabolism. These substrates mainly include NSAIDs (nonsteroidal anti-inflammatory drugs) such as ibuprofen, as well as S-warfarin, tolbutamide, and paracetamol. This means that these drugs have the ability to form strong hydrogen bonds or ionic interactions within a specific distance from the site of metabolism, which is important for their interaction with the CYP2C9 enzyme.

7. Which of the statements best describes the properties of the P450 enzymes?

Dimeric proteins, 40 - 50,000 MW; haem group with F2 in 2+ state

Multimeric proteins, 40 - 45,000 MW; protoporphyrin XI haem group

Monomeric proteins 40 - 50,000 MW; protoporhyrin IX haem prosthetic group

The P450 enzymes are monomeric proteins with a molecular weight of 40 - 50,000 MW. They contain a protoporhyrin IX haem prosthetic group.

Explanation

The P450 enzymes are monomeric proteins with a molecular weight of 40 - 50,000 MW. They contain a protoporhyrin IX haem prosthetic group.

8. Which of these statements best describes the distribution of P450?

Highest levels in liver; lower levels in kidney and lung; some forms e.g. CYP1A1 only extrahepatic

Highest levels in liver; lower levels in kidney and intestine; some forms e.g. CYP3A1 only extrahepatic

Highest levels in liver; lower levels in gut and duodenum; some forms e.g. CYP1A2 only extrahepatic

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Explanation

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9. How is the half life of diclofenac increased by P450 metabolism?

Fl atom moved from position 4 to 6 - preferential site of oxidation lost - shorter T1/2

Cl atom moved from position 6 to 4 - preferential site of reduction lost - longer T1/2

Cl atom moved from position 4 to 6 - preferential site of oxidation lost - longer T1/2

The movement of the Cl atom from position 4 to 6 in diclofenac leads to the loss of the preferential site of oxidation. This means that the drug is less susceptible to being metabolized by P450 enzymes, resulting in a longer half-life (T1/2). Therefore, the correct answer is that the Cl atom moved from position 4 to 6, leading to the loss of the preferential site of oxidation and a longer half-life.

Explanation

The movement of the Cl atom from position 4 to 6 in diclofenac leads to the loss of the preferential site of oxidation. This means that the drug is less susceptible to being metabolized by P450 enzymes, resulting in a longer half-life (T1/2). Therefore, the correct answer is that the Cl atom moved from position 4 to 6, leading to the loss of the preferential site of oxidation and a longer half-life.

10. Which three factors contribute to determining metabolism by specific isoforms?

Topography of P450 active site; degree of steric hindrance of access to Fe-O complex; how easily substrate will react

Topography of substrate active site; degree of steric hindrance of access to P450 active site; ease of reaction

The three factors that contribute to determining metabolism by specific isoforms are the topography of the P450 active site, the degree of steric hindrance of access to the Fe-O complex, and how easily the substrate will react. These factors affect the binding and accessibility of the substrate to the active site, as well as the ease with which the reaction can occur.

Explanation

The three factors that contribute to determining metabolism by specific isoforms are the topography of the P450 active site, the degree of steric hindrance of access to the Fe-O complex, and how easily the substrate will react. These factors affect the binding and accessibility of the substrate to the active site, as well as the ease with which the reaction can occur.