Cytochromes P450

Question 1

What general reaction does a P450 system catalyze?

Answer 1

Hydroxylation

Question 2

What prosthetic group is found in all P450 enzymes?

Answer 2

Heme (Fe^3+)

Question 3

Name four biological molecules that are substrates for P450 enzymes.

Answer 3

Long-chain fatty acids, steroids, bile salts, cholecalciferol (Vitamin D), Heme

Question 4

Name four xenobiotics (general categories are o.k.) that are substrates for P450’s.

Answer 4

Pesticides, Defoliants, Aromatic Hydrocarbons and Drugs such as:

Analgesics (tylenol)
Psychotropics
Anesthetics
Diuretics
Receptor ligands

Question 5

Define the term “induction” in the context of P450 biology.

Answer 5

The synthesizing of P450 enzymes in response to the presence of their substrate.

Question 6

Describe the ways in which drugs can change the activities of P450 enzymes.

Answer 6

…? Not sure if this is correct?

CYP450 makes formerly lipid soluble substrates more polar (water soluble) and more receptive to derivitization (because of hydroxyl)

Question 7

Discuss the importance of P450 systems in

drug metabolism. Include consideration of patient lifestyle and polypharmacy (many drugs)

Answer 7

CYP450 is central to drug metabolism, determining half-lives and extent of drug activation. Most importantly, there can be considerable cross-reactivity betweeh CYP450s (due to lack of substrate specificity), that leads to undesirable drug interactions.

Question 8

What is the subcellular location of P450 systems in the liver?…in the adrenal?

Answer 8

Liver (and all other L things) = Smooth ER

Adrenal = Mitochondrial membrane

Question 9

Discuss the factors that govern the levels of P450 activity.

Answer 9

Because of the idiosyncrasies of drug metabolism, personal factors, such as genetic background, sex, age, pregnancy, nutritional status, and diseases govern P450 activity.

Question 10

Patient X is given a pill that only works as a therapeutic agent after it has been metabolized, what category does the original pill fall under?

Answer 10

a prodrug

Question 11

True or False: Cytochrome P450 is inducible by substrates and specific to the substrate?

Answer 11

False: CYP450 synthesis IS inducible by substrates, but it tends to be Promiscuous (not very specific) with regard to substrate.

Question 12

What are the three metabolic types for Cytochrome P450?

Answer 12

Poor Metabolizer (PM). Extensive Metabolizer (EM), Ultra-Rapid Metabolizer (URM)

Question 13

Acetaminophen when taken a therapeutic doses can be convered to it’s conjugated metabolite and what other unfortunate substance?

Answer 13

a hepatotoxic metabolite