Detoxification Flashcards Preview

Liver + Friends Physiology > Detoxification > Flashcards

Flashcards in Detoxification Deck (15):

What are xenobiotics?

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


What is a microsome?

A fragment of ER and attached ribosomes. q


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

Microsomal enzymes are found in SER.

Cytochrome P450


What are phase I reactions?

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


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.


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

Found in cytoplasm and mitochondria.

Protein oxidases, transferase, alcohol dehydrogenase


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.


Where do phase I and phase II reactions occur?

In the liver


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


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


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

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


Which enzymes and coenzymes are used in glucuronidation?

Enzyme: Glucuronosyltransferase
Coenzyme: UDPGA

Products of this reaction are called glucuronides.


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.


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.


Describe alcohol metabolism.

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

ADH = alcohol dehydrogenase

ALDH = aldehyde dehydrogenase