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70 Cards in this Set
- Front
- Back
List routes of entry of toxins into the body
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produced in the body, absorbed through GIT, absorbed through the lungs, absorbed through the skin, absorbed into blood via wounds
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List some factors which can affect the toxicity of a substance
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pathway of administration, time of exposure, number of exposures, physical form of toxin, genetic makeup of an individual
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what factors determine the toxicity of a substance?
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toxins are inherintly toxic or can be toxic metabolic products
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list the two broad classes of toxic substances
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can exert effects by binding to protiens or DNA or as analouges of essential chemicals
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list three means by which a toxin can exert its effect
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phase I: desulphuration, methylation, oxidation and epoxide foration
phase II: conjugation and glucuronidation |
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what is the most common conjugate used in phase II reactions
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glucuronate
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What is the purpose of phase II reactions
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to make substances more polar and water soluble
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What metal ion is important for cytochrome p450 enzyme activity?
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Fe
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What is the end product of ethanol degradation
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acetly CoA
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Name two porphyrin-based, naturally occurring chelates
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haem and chlorphyll
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Name two diseases of copper metabolism
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Wilsons disease and Menke's disease
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What are bone seeking isotops also called?
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radionuclides
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Why is curare toxic?
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because it is an acetylcholine analogue which binds to acetylcholine receptors, thus preventing it from having an effect
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where in the body are fat soluble toxins sometimes stored?
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in any fatty tissue: eg adipose tissue, nervous system tissue, and bones
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What type of reactions are phase I reactions? Give two examples
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transformations: eg. oxidation, reduction, hydroxylation, methylation, desulphuration
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What type of reactions are phase II reactions? Give an example
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conjugations eg. glucuronidation
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Where in the cell do phase I reactions occur?
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smooth ER of hepatocytes
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What two substances do phase I reactions need?
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oxygen and NADPH
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What type of enzymes catalyses phase II reactions
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Transferases catalyse phase II reactions
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What enables cytochrome P450 enzymes to catalyse redox reactions?
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Haem containing Fe catalyse redox reactions
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Which part of protein molecules facilitates their chelating action
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Excess copper produces iron overload and increases susceptibility to free radical attack.
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Explain the toxicity of radionuclides
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Radionuclides can form cations similar to calcium and so are incorporated into bone where they undergo radioactive decay and emit radiation causing mutation in nearby cells.
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Define Toxicology
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the study of poisonous substances and their effect on the body
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Define Xenobiochemistry
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study of foreign substances and their effect on the body
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Define a Xenobiotic
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a foreign substance having no known biological value
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What does a protein binding substance do?
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Binds to an enzyme, this inactivating it and its particular metabolic pathway
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What does an analogue of a natural substance do?
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Prevents that natural substance from having its normal effect
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Give an example of an analogue
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Dicoumarol os a vit. K analogue that causes bleeding disorders by blocking vit. K's action.
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What is Biotransformation?
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Detoxification and elimination of foreign substances
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Where does biotransformation occur?
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predominantly in the liver
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T/F Phase 1 of detoxification often results in a more active chemical than the original
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True
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T/F Metabolism by the liver generally results in a substance which is more water soluble and often more acidic
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True
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List the Phase 1 reactions:
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Transformation reactions: (oxidation, reduction, or hydrolysis)
Hydroxylation Epoxide formation Dealkylation Deamination Reduction Methylation Desulphuration |
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List the Phase 2 reactions:
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Conjugate Formation:
Glucuronidation Esterification with Sulphate Amidation with Gly & Glu |
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Where is the conjugate secreted?
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In the bile or the urine
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What is the result of phase 1 reactions?
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usually increase in the polarity and often a decrease in the biological activity or toxicity of the substance
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Where do Phase 1 reactions occur?
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In the smooth endoplasmic reticulum of hepatocytes
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What is a common catalyst of the oxidative reactions of Phase 1?
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cytochrome P450
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What do the reactions of phase 1 require to act as a reducing agent?
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molecular oxygen and NADPH
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What do Phase 2 reactions result in?
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formation of conjugates.
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What enzymes are involved in Phase 2 reactions?
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transferases
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Define Glucuronidation
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the addition of glucuronic acid
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T/F Glucuronate is highly polar
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True
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What is cytochrome P450?
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a class of enzymes that contain a haem group as the redox-active coenzyme
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Name some metabolic processes that cytochrome P450 systems are involved in:
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biosynthesis of steroid hormones, leukotrines, prostaglandins, and UFAs
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The degredation of .................. in the liver uses the cytochrome P450 system
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ethanol
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How is ethanol excreted?
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through the lungs, kidney, and skin, with most being oxidised in the liver by alcohol dehydrogenae
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How is ethanol converted to ethenal?
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Via alcohol dehydrogenase, or by the cytochrome P450 system.
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What is Ethanal oxidised to?
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acetate
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T/F Acetate can not be used as an energy source
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False
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Describe why ethanal is able to be used as an energy source
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It is converted to acetyl-CoA by acetate-CoA ligase
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What are the effects of high levels of acetyl-CoA and NADH?
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they inhibit the citric acid cycle,a dn stimulate the synthesis of neutral fats and cholesterol.
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What substances are able to form coordination complexes?
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Ammonia and Phosphates
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What does a donor molecule (lignand) do?
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Donates electrons to stabalise metal ions
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If two ligand molecules are bound together they are known as ....
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chelates (bidentate, tridentate, tec).
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Because chelates have a high affinity for calcium, they may provoke...
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hypocalcaemia
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List 2 naturally occuring chelates
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Porphyrins such as haem (chelates with iron) and chlorophyll (chelates with magnesium)
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What is metallothioneine?
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A cysteine-rich proteins found in the liver with a high affinity for divalent ions.
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What is copper required for?
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certain oxido-reductases incl. cytochrome oxidases, superoxide dismutase, tyrosinase, dopamine b-hydroxylase, and lysly oxidase
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What is caeruloplasmin?
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a copper binding protein formed in the liver.
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What is the function of caeruloplasm?
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transports copper to the liver, and catalyses the oxidation of Fe(II) to Fe(III).
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List some ways that mercury is able to enter the body
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through the lungs, skin, and via the digestive system
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Where is metallothionein found?
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In the Kidneys
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What is the function of metallothionein?
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to bind mercury tightly until it is excreted.
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How is lead able to enter the cells?
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via hormone or voltage gated calcium channels.
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How might lead cause anaemia?
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Inhibiting the biosynthesis of haem by acting on several of the enzymes which are essential to haems production
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What is the most abundant metal?
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Aluminium
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T/F Aluminium readily forms complexes with amino acids
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True
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What are radionuclides?
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a group of metals that cause mutation to bone cells
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What disease is Caesium-137 linked with?
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Leukaemia
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