Biotransformation and Excretion of Toxicants

Phase I of xenobiotic metabolism = Introduces a polar group into the molecule Phase II of xenobiotic metabolism = Conjugates the xenobiotic to make it more water-soluble Hydrophilic metabolites = Reduced ability to cross membranes Lipophilic xenobiotics = Can penetrate lipid membranes

Biotransformation = Changes substances from hydrophobic to hydrophilic Introduction of a polar group in phase I = Increases water solubility of xenobiotics Reduced reabsorption by cells in elimination organs = Associated with altered toxicant distribution to tissues Lipoproteins in body fluids = Transport lipophilic xenobiotics

Chemically distinct metabolites = Result from biotransformation Increased hydrophilicity after biotransformation = Reduces membrane crossing ability Nonspecific enzymes in xenobiotic metabolism = Carry out the metabolism in two phases Introducing a polar group in phase I = Makes xenobiotics suitable for phase II reactions

<p>Skin = Low capacity Intestines = Medium capacity Liver = Highest capacity Lungs = Medium capacity</p> Signup and view all the answers

<p>Microsomal enzymes = Associated with phase I reactions Cytosolic enzymes = Associated with phase II reactions Cytochrome P-450 = Catalyzes phase I reactions Glucuronidation = Process in phase II reactions</p> Signup and view all the answers

<p>Activation mechanism = Intermediates or final products are more toxic than the parent compound Detoxication mechanism = Generally a detoxication process but can lead to more toxic products in some cases Conjugation product = Water-soluble product of phase II reactions Conjugation reactions = Phase II reactions that produce a more water-soluble metabolite</p> Signup and view all the answers

<p>Age, gender, nutrition, disease, time of day = Factors affecting biotransformation effectiveness Nutritional status = Affects biotransformation as seen in nonhuman studies Hepatitis = Reduces hepatic biotransformation capacity Liver impairment = Poses serious health consequences due to reduced biotransformation capacity</p> Signup and view all the answers

<p>Oxidation = Toxicant loses electrons in phase I reactions Reduction = Toxicant gains electrons in phase I reactions Hydrolysis = Process that cleaves toxicant into simpler molecules in phase I reactions Glucuronidation = Addition of glucuronide to toxicant or phase I metabolite in phase II reactions</p> Signup and view all the answers