Detoxification Flashcards Preview

Liver + Friends Physiology > Detoxification > Flashcards

Flashcards in Detoxification Deck (15):
1

What are xenobiotics?

Foreign chemical substances not normally found in the body and cannot be used for energy requirements e.g. drugs.

2

What is a microsome?

A fragment of ER and attached ribosomes. q

3

Name a microsomal enzyme. Which organelle are they found in?

Microsomal enzymes are found in SER.

Cytochrome P450

4

What are phase I reactions?

Biotransform substances via oxidation, reduction and hydrolysis to make them more polar.
Most use microsomal enzymes.

5

What are phase II reactions?

Glucuronidation - addition of glucuronic acid, acetylation and sulfation. These are conjugation reactions that increase water solubility (more hydrophilic) of drug substances.
Most use non-microsomal enzymes.

6

Name a non-microsomal enzyme. Which organelles are they found in?

Found in cytoplasm and mitochondria.

Protein oxidases, transferase, alcohol dehydrogenase

7

What is the purpose of phase I and phase II reactions?

They metabolise drugs by making them more polar so they cannot pass through cell membranes and are excreted instead.

8

Where do phase I and phase II reactions occur?

In the liver

9

Describe what happens in a phase I reaction in relation to drugs.

Aims to make drug more hydrophilic so it can be excreted by the kidneys. Does this by adding a hydroxyl group to the drug. This can have the following effects:
Inactivate drug
Further activate drug
Make a drug into a reactive intermediate

10

Describe the characteristics of cytochrome P45 enzymes.

They are a type of microsomal enzyme involved in phase I reactions.
Examples: CYP 1A2

1st Number = family of enzyme
Letter = indicates subfamily
2nd Number = Individual genes involved

11

Give the overall reaction for the action of cytochrome P450 reductase.

NADPH + H+ +O2 + RH > NADP+ +H2O + R-OH

12

Which enzymes and coenzymes are used in glucuronidation?

Enzyme: Glucuronosyltransferase
Coenzyme: UDPGA

Products of this reaction are called glucuronides.

13

Describe aspirin metabolism.

Phase I: Aspirin is a pro-drug so is activated upon metabolism.
Aspirin + H2O > Salcylic acid + Ethanoic acid

Phase II: Conjugated with glycine or glucuronic acid. Forms a range of ionised metabolites than won't be passively absorbed and can be excreted by the kidney.

14

Describe paracetamol metabolism, including what happens in an overdose.

Predominantly metabolised via Phase II = conjugated with glucuronic acid + sulphate.

However, if levels of glucuronic acid + sulphate are low, paracetamol will undergo Phase I metabolism via oxidation to produce toxic NAPQI. This is removed with glutathione, however in overdoses, glutathione stores run low, resulting in toxicity.

15

Describe alcohol metabolism.

Ethanol (ADH) > Acetaldehyde (ALDH) > Acetate > CO2 + H2O

ADH = alcohol dehydrogenase

ALDH = aldehyde dehydrogenase