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70 Cards in this Set

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