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.
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:
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?
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.