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1.) fate of xenobiotic -- central role of metabolism

1.) fate of xenobiotic -- central role of metabolism Uptake/Transport --------> Metabolism -------------> Excretion Or Storage 2.) xenobiotic converted by 2-step process (a.) Phase I biotransformations yield primary metabolite -- oxidation -- reduction

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1.) fate of xenobiotic -- central role of metabolism

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  1. 1.) fate of xenobiotic -- central role of metabolism Uptake/Transport --------> Metabolism -------------> Excretion Or Storage 2.) xenobiotic converted by 2-step process (a.) Phase I biotransformations yield primary metabolite -- oxidation -- reduction -- hydrolysis (b.) Phase II conjugations yield product destined for excretion -- glycine -- glutamine -- glutathione -- glucuronate

  2. 3.) Phase I biotransformations (a.) oxidations -- hydroxylation -- dealkylation -- deamination -- sulfoxide formation

  3. (b.) reductions -- hydrogenation -- azo reduction

  4. (c.) hydrolysis -- spltting of ester bonds -- splitting of amide bonds

  5. 4.) Phase II conjugations (a.) primary metabolite/endogenous substance/increased water solubility

  6. 5.) Phase I biotransformations (a.) occur mostly in the liver (b.) mediated by MFOs called cytochromes P450 (c.) occur in endoplasmic reticulum (liver microsomes) (d.) mechanism (e.) very broad range of substrates accomodated -- aliphatic hydroxylation -- aromatic hydroxylation -- aliphatic epoxidation -- aromatic epoxidation -- N-oxidation -- sulfoxidation -- dealkylation -- deamination -- dehalogenation 6.) Phase II conjugations (a.) occur in cytosol

  7. 7.) Phase I reactions generate reactive electrophiles (a.) problem with halogenated alkenes or carbon tetrachloride (b.) electrophiles react with nucleophiles - binding to cellular constituents (c.) endogenous antioxidants act as free radical scavengers -- vitamin C -- vitamin E -- glutathione (d.) reactive oxygen species can be handled enzymatically -- superoxide dismutase -- catalase -- glutathione reductase

  8. 8.) Bacteria can use organic compounds as carbon source for growth (a.) differentiate from detoxification (b.) benzene conversion to acetaldehyde+pyruvate; yield CO2+H2O (c.) general metabolic mechanisms -- direct oxidative, reductive or hydrolytic attack -- cometabolic transformation (TCE epoxidation, e.g.) -- respiratory electron transfer 9.) Goals of bioremediation as a strategy in toxicity reduction

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