detoxification pathways

Question 1

phase I reactions

Answer 1

prepares molecule for phase II, by creating or exposing an OH group. So phase II can attach something to oxygen. Reduction, oxidation, hydroxylation, and hydrolysis. Enzyme: cytochrome p450, monooxyganase

Question 2

phase II

Answer 2

conjugation, more water soluble, excretable. Could be conjugation, sulfating, methylation, glucuronidation. Enzyme: transferases

Question 3

describe a typical phase 1 to phase II reaction

Answer 3

Typical: hydroxylation followed by sulfating. Inactivating original molecule. Detoxifying it and getting it out of the body as a waste product.

Glutatione S transferase (attach through sulfur), to make molecule more water soluble.

Question 4

how does body use phase II reaction to inactivate steroid hormones

Answer 4

Body gets rid of them by conjugating them, attaching groups. Catalyzed by transferases. Often sulfated. Makes more water soluble. Not detoxifying bc toxic, but want to get out of body.

Question 5

what is PAPS

Answer 5

phosphoadenosine phospho sulfate

Question 6

what is PAPS

Answer 6

a sulfate donor

Question 7

where does the sulfate come from in PAPS

Answer 7

cysteine

Question 8

Sulfite vs sulfate (chemical formula)

Answer 8

SO3 and SO4. both neg -2 charge

Question 9

draw PAPS schematic

Answer 9

see notes

Question 10

sulfite oxidase

Answer 10

requires molybdenum in active site. oxidizes sulfite to sulfate. requires ATP

Question 11

what is the oxidizing agent in the sulfite oxidase reaction

Answer 11

cytochrome c. those electrons then go to the electron transport chain

Question 12

3 major sites for biotransformation of xenobiotic compounds

Answer 12

liver, small intestine/enterocytes, and kidney cells

Question 13

how does detoxifcation sometimes back fire

Answer 13

phase 2 proceed phase 1 and turns the compond into something really toxic

Question 14

major Cytochprome p450 enzyme associated with detox pathways

Answer 14

CYP3A4

Question 15

grapefruit juice and metabolism of drugs

Answer 15

CYP3A4 inhibits ( likely dosing will be to high… not enough cyp3a4 to break shit down).

Question 16

drug interaction with st. johns wort

Answer 16

induces CYP3A4… not enough drug, constantly breaking it down.

Question 17

acetaminophen toxicity (toxic dose)

Answer 17

changes into NAPQI and that compound causes liver damage

Question 18

whats the antidote for acetominophen toxicity

Answer 18

NAC n-acetyl cysteine

Question 19

someone who drinks more alcohol and acetominophen dosing

Answer 19

CYP2E1 (MEOS) inducible/more so.. if chronically drinking, converts acetaminophen to NAPQI/affects how well liver cell works.