Tox Path

Question 1

Phase 1 of liver detoxification

Answer 1

(Cytochrome p450 enzymes)
Oxidation, reduction, hydrolysis, hydration, dehalogenation

Question 2

Phase 2 of liver detoxification

Answer 2

(Conjugation pathways)
Sulfonation, glucuronidation, glutathione conjugation, amino acid conjugation, acetylation, methylation

Question 3

Key enzyme for phase 1 of liver detoxification

Answer 3

Cytochrome p450 enzymes (CYPs)

Question 4

Where do phase 1 reactions take place in liver detoxification?

Answer 4

ER (microsomal fraction)

Question 5

Where are lesions of reactive metabolites most observed in the liver?

Answer 5

Centrilobular (since CYPs are mainly located there)

Question 6

Cofactor and enzyme for glucuronidation

Answer 6

UDPGA
UGTs

Question 7

Cofactor and enzyme for glutathione conjugation

Answer 7

GSH (glutathione)
GSTs

Question 8

Cofactor and enzyme for sulfonation

Answer 8

PAPS
SULTs

Question 9

Carbon monoxide toxicity

Answer 9

Product of carboxyhemoglobin
Cherry red color of skin and mucous membranes

Question 10

Lead toxicity - MOA and physiologic consequences

Answer 10

•Binds to sulfhydryl groups and interferes with Ca metabolism
•Inhibition of ferrochelatase, defect in Hgb synthesis
•CNS: demyelination
•Kidney: tubular necrosis with intranuclear lesions

Question 11

Acetaminophen detoxification occurs in which organ and during which phase?

Answer 11

Liver, phase 2

Question 12

Why are cats susceptible to acetominiphen toxicity?

Answer 12

Low glucuronyl transferases

Question 13

Which enzyme metabolizes the minority of acetaminophen?

Answer 13

CYP2E

Question 14

Acetylsalicylic acid toxicity most often appears in which organ(s) and what is a major consequence?

Answer 14

GIT, kidney
Prevention of platelet aggregation related to COX2 inhibition

Question 15

Acetaminophen (minority) metabolism toxicity steps

Answer 15

CYP2E > NAPQI > lipid peroxidation > necrosis

Question 16

Genetic mutation that predisposes to hyperthermia and process

Answer 16

RYR1
RYR1 > leaking of Ca into sarcoplasm > muscle contraction/heat production

Question 17

UV-B irradiation

Answer 17

Affects pyrimidine dimer formation (cytosine, thymine, uracil)

Question 18

DNA adducts

Answer 18

Any chemical that covalently links to DNA
-aflatoxins, brackenfern, chemotherapeutics, pyrrolizidine alkaloids
-lipid peroxidation, xenobiotic metabolism

Question 19

Bromethalin toxicosis

Answer 19

Non-coagulating, neurotoxin rodenticide
Uncouples oxidative phosphorylation

Question 20

Copper toxicosis

Answer 20

Copper-induced membrane lipid peroxidation and edema secondary to impaired osmoregulation

Question 21

Acetaminophen toxicity

Answer 21

N-acetyl-p-benzoquinone imine binds to glutathione and protein sulfhydryls

Question 22

PA toxicity

Answer 22

Highly reactive DHP alkaloids, bind at guanine and adenine residues

Question 23

Strychnine toxicosis

Answer 23

Inhibits release of neurotransmitter glycine at the postsynaptic neuron

Question 24

Organophosphate toxicity

Answer 24

Inhibition of acetylcholinesterase