PHIL 2130 Lecture Notes - Lecture 12: Polycyclic Aromatic Hydrocarbon, Aromatic Amine, Mephenytoin
6 May 2020
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Document Summary
Classic substrates: polycyclic aromatic hydrocarbons or amines (carcinogens) Induced via the ah (aryl hydrocarbon) receptor and especially by dioxin and pcbs, but also tobacco smoke and omeprazole: cyp1a1- not constitutively in liver but can be induced, cyp1a2-metabolizes caffeine, aromatic amine carcinogens, and aflatoxin. Oxidizes nicotine and likely a significant determinant of abuse potential (rapid metabolizers have to smoke more to sustain nicotine levels and it is harder for them to quit) Cyp2c19- polymorphic; metabolizes mephenytoin, omeprazole, diazepam, and clopidogrel. Polymorphic (7% slow in north america, but only 1% in orientals) Oxidizes small molecules, such as alcohol, acetaminophen and chloroform. Induced by alcohol and this may be a risk factor for acetaminophen toxicity. This isosyme makes up a significant fraction of p450s b weight and it also has the broadest substrate specifity. Its binding pocket is also quite large so it can oxidize a large substrate like cyclosporine.
