HLTH340 Lecture Notes - Lecture 2: Cyp2D6, Mptp, Paraquat

• School: University of Waterloo
• Department: Health Studies
• Course: HLTH340
• Professor: Brian Laird

Document Summary

Induced by mptp toxicity to the sn (substantia nigra) Mptp: toxic to brain neurons in brainstem sn, contaminated synthetic heroine in fentanyl, dopamine (da) producing neurons in sn = damaged/destroyed, can cause cell death. *ion trapping of mptp/mpp+ at the blood brain barrier via mao-b oxidation* Mptp -> cyp2d6 (removes m) -> ptp (non-toxic) Mptp -> mao-b (toxic, removes t) -> mpp+ (toxic) -> cyp2d6 (removes m) -> pp (non-toxic: bioactivation, unintentionally making mptp more toxic by converting to mpp, less of mpp+ to cause cell death. Mpp: can mimic dopamine (da, bioactivated metabolite of mptp, bbb -> passive diffusion, neurotoxic via complex i inhibition, ros, parkinsonism. In vesicle: mpp+ through da, oxidation of da, cell membrane damage. Complex i in mitochondrion makes mpp+ very toxic -> disrupt etc. Da neuron uptake of mpp+ or agricultural toxicants (rotenone, paraquat) affects mitochondrial etc -> no atp produced. Rotenone: pesticide, bbb -> passive diffusion, neurotoxic via complex i inhibitor, ros.