03_Biochem_physiol_effects_1_S09

03_Biochem_physiol_effects_1_S09 - Bruce Greenberg B2-154...

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Bruce Greenberg B2-154 Ext: 33209 [email protected]
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Identifying the key mechanism can be a challenge
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Biochemical and Physiological Effects of Chemicals – Part 1 Chapters 6, 7 and 14 Metals and Radioactive isotopes 1. Types of effects 2. Negative and positive effects of contaminants on a chemical class basis 3. Modifying factors
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Types of mechanisms (P. 113) Negative effects Narcosis: Membrane damage Biochemical toxicity: Enzyme inhibition Reactive oxygen species: Oxidative damage Endocrine toxicity: Hormone mimic Genotoxicity: Mutation, Stop replication Positive (or protective) effects Detoxification: Degradation and excretion Acclimation: Defense responses Toxic effects begin with interactions with biomolecules Biochemical effects are important
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Variables in toxicity mechanisms 1. Organism 2. Chemical 3. Concentration/dose 4. Modifying factors Chemical approach
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Metals Negative impacts: 1. Dose dependant: Different mechanisms function at different levels of the metals. All metals are toxic in excess 2. Metal dependant: Metabolic vs. non-metabolic Divalent vs. monovalent Different mechanisms in general: Hg much different than Pb Different toxicities: e.g. Class A vs. Class B 3. Environment dependent: Binding in aquatic systems Organometallics: Methyl mercury, tributyl tin
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Classes of Metals Required nutrients Metabolic Nutrients Iron, Calcium, Zinc*, (Sodium, Potasium) Trace nutrients (micro nutrients) Selenium*, Copper*, Cobalt, Magnesium, Manganese Non-metabolic Lead*, Cadmium*, Tin*, Mercury* *Metals that are toxic and prevalent: Therefore, of environmental concern
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Classification of Metals by Biologically Relevant Properties H He Li Be B C N O F Ne Na Mg Al Si S Cl Ar K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po AT Rn Fr Ra Ac Rf Ha Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Lu Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr from Nieboer and Richardson 1980 blue = Class A metals red = Class B metals yellow = borderline between A and B pink = Class B or borderline, depending on oxidation state
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Functions of Metals in Metabolism Enzyme co-factors Redox active centers in many enzymes Fe: Electron transport, SOD, Cytochrome P450 Zn: SOD Mg, Mn: Photosynthesis Cu: Electron transport Ca: Cell signaling Ca, Na, etc: Substrates in ion pumps Structural components of enzymes Fe: Hemoglobin, Cell structure Zn: Zn fingers in transcription factors Ca: Bone structure, Cell structure
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metal metabolic function (P. 126, 127, 135, 145) Block essential function of biomolecules e.g. Ion pumps: Divalent metals inhibit Ca pumps Displace essential metal co-factors e.g. Cd can replace Cu in electron transport enzymes Modify configuration of biomolcules: Zn can be replaced by Cd in Zn fingers DNA: metal binding to nucleotide bases. Base mismatching and chromosomal damage
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This note was uploaded on 07/10/2010 for the course BIOL 354 taught by Professor Brucegreenberg during the Spring '09 term at Waterloo.

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03_Biochem_physiol_effects_1_S09 - Bruce Greenberg B2-154...

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