liver detoxification

Question 1

what is a xenobiotic?.

Answer 1

a foreign chemical substance that can be absorbed across the lungs, skin or ingested.

drugs are considered xenobiotics for a drug to be pharmacologically active it must be lipophilc

Question 2

what is a microsomal enzyme?

Answer 2

• an enzyme located on smooth endoplasmic reticulum mainly involved in phase 1 reactions but phase 2 reaction = glucuronidation
• activity can be induced and inhibited

Question 3

what is a non-microsomal enzyme?

Answer 3

located in the cytoplasm and mitochondria

• non-specific so can be involved in phase 1 and 2
• all conjugation reactions apart from glucuronidation
• non-inducable

Question 4

why do we metabolise drugs?

Answer 4

because most drugs are excreted by the kidney& lipophilic molecules aren’t effectively removed so metabolising them makes them more polar and easier to excrete in the liver

Question 5

what takes place in phase 1 reactions?

Answer 5

functionalisation

• non-synthetic catabolic reactions
• oxidation, reduction, hydrolysis
• introduces reactive group
• small increase in hydrophilicity

Question 6

what is the main enzyme involved in phase 1 reactions? & what does it do?

Answer 6

cytochrome P450

it’s a type of microsomal enzyme with a haem group to oxidise substances which has many different isoforms for different specific reactions

Question 7

what do phase 1 reactions do to a drug?

Answer 7

-inactivate drug
-further activate drug
activate durg from pro-drug
-make a drug into a reactive intermediate (could be toxic or carcinogenic)

Question 8

what are phase 2 reactions?

Answer 8

synthetic anabolic reactions

• known as conjugation reactions
• catalysed by transferases
• causes a significant increase in hydrophilicity

Question 9

describe glucuronidation.

Answer 9

glucuronosyltransferase (UGT) a microsomal enzyme attaches a molecule of glucuronic acid to a molecule