Tox Path Flashcards
Phase 1 of liver detoxification
(Cytochrome p450 enzymes)
Oxidation, reduction, hydrolysis, hydration, dehalogenation
Phase 2 of liver detoxification
(Conjugation pathways)
Sulfonation, glucuronidation, glutathione conjugation, amino acid conjugation, acetylation, methylation
Key enzyme for phase 1 of liver detoxification
Cytochrome p450 enzymes (CYPs)
Where do phase 1 reactions take place in liver detoxification?
ER (microsomal fraction)
Where are lesions of reactive metabolites most observed in the liver?
Centrilobular (since CYPs are mainly located there)
Cofactor and enzyme for glucuronidation
UDPGA
UGTs
Cofactor and enzyme for glutathione conjugation
GSH (glutathione)
GSTs
Cofactor and enzyme for sulfonation
PAPS
SULTs
Carbon monoxide toxicity
Product of carboxyhemoglobin
Cherry red color of skin and mucous membranes
Lead toxicity - MOA and physiologic consequences
•Binds to sulfhydryl groups and interferes with Ca metabolism
•Inhibition of ferrochelatase, defect in Hgb synthesis
•CNS: demyelination
•Kidney: tubular necrosis with intranuclear lesions
Acetaminophen detoxification occurs in which organ and during which phase?
Liver, phase 2
Why are cats susceptible to acetominiphen toxicity?
Low glucuronyl transferases
Which enzyme metabolizes the minority of acetaminophen?
CYP2E
Acetylsalicylic acid toxicity most often appears in which organ(s) and what is a major consequence?
GIT, kidney
Prevention of platelet aggregation related to COX2 inhibition
Acetaminophen (minority) metabolism toxicity steps
CYP2E > NAPQI > lipid peroxidation > necrosis
Genetic mutation that predisposes to hyperthermia and process
RYR1
RYR1 > leaking of Ca into sarcoplasm > muscle contraction/heat production
UV-B irradiation
Affects pyrimidine dimer formation (cytosine, thymine, uracil)
DNA adducts
Any chemical that covalently links to DNA
-aflatoxins, brackenfern, chemotherapeutics, pyrrolizidine alkaloids
-lipid peroxidation, xenobiotic metabolism
Bromethalin toxicosis
Non-coagulating, neurotoxin rodenticide
Uncouples oxidative phosphorylation
Copper toxicosis
Copper-induced membrane lipid peroxidation and edema secondary to impaired osmoregulation
Acetaminophen toxicity
N-acetyl-p-benzoquinone imine binds to glutathione and protein sulfhydryls
PA toxicity
Highly reactive DHP alkaloids, bind at guanine and adenine residues
Strychnine toxicosis
Inhibits release of neurotransmitter glycine at the postsynaptic neuron
Organophosphate toxicity
Inhibition of acetylcholinesterase
