Statistics for forensic toxicology - mechanisms of toxicity

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  • The average score is 48 of 48

Answer Stats

HintAnswer% Correct
activation of Ca2+-dependent hydrolytic enzymes (leads to disintegration of membranes, proteins etc.)
100%
activation of Ca2+-dependent proteases (convert xanthine dehydrogenase to xanthine oxidase, which also produces superoxide and hydrogen peroxide)
100%
activation of constitutively-expressed nitric oxide synthases in neuronal and endothelial cells (increases NO production, which reacts with superoxide to form highly reactive peroxynitrite)
100%
how are these species generated indirectly?activation of cytochrome P450, increased intracellular Ca2+
100%
how do these species cause oxidative stress?activation of dehydrogenases in the TCA cycle (increases electron output via the electron transport chain, causing increased production of superoxide)
100%
what is Ca2+ involved in?activation of enzymes (e.g. TCA cycle), cytoskeletal polymerisation, muscle contraction, neurotransmission, regulation of signal transduction and exocytosis, transporters
100%
how are these species generated directly?activation of foreign compounds (e.g. benzene), redox cycling (e.g. paraquat), transition metals, inhibition of mitochondrial electron transport (blocking the electron transport chain)
100%
what do we need ATP for?active transport, especially ion transport, biosynthetic reactions, cell division, cell morphology, cytoskeletal polymerisation, essential part of DNA, muscle contraction, regulation of signal transduction
100%
what other issues can these species cause?affecting the function of oxidise proteins, mutate DNA causing cellular dysfunction and reducing ATP synthesis, lipid peroxidation, cell swelling, cell lysis
100%
when does calcium become toxic in the cytoplasm?at high levels
100%
what are the 3 primary causes of necrosis?ATP depletion
100%
why are the levels of calcium ions tightly regulated within a cell?because it is so important and so reactive
100%
what are four consequences of
excitotoxicity?
depletion of ATP (Mitochondrial ATP production is decreased; activation of Ca2+ ATPase uses ATP)
100%
what kind of 'essential function disruption' are these causes?disruption to energy generation & protein synthesis
100%
what do these species do to ATP?drain the ATP reserves
100%
endoplasmic reticulum Ca2+ ATPase
100%
what eventuates?eventually the lipid fragments release reactive aldehydes and more free radicals
100%
excitotoxicity
100%
what is the consequence of increased intracellular Ca2+?excitotoxicity
100%
what are the 4 mechanisms of calcium removal from the cell?extracellular Ca2+ ATPase
100%
extracellular Na+/Ca2+ exchanger
100%
what will dying cells do during apoptosis?fragment into membrane-bound apoptotic bodies
100%
inhibition of ADP phosphorylation (eg. DDT)
100%
what are the 4 key mechanisms by which ATP can be depleted?inhibition of electron transport (eg. cyanide inhibits cytochrome oxidase)
100%
inhibition of oxygen delivery to the ETC (eg. cocaine, carbon monoxide)
100%
how can oxidative stress be avoided within a cell?it can be quenched by enzymes
100%
what affect will this have on neighbouring cells?it can trigger an inflammatory response or long term inflammation
100%
how does it stop oxidative stress?it converts the superoxide radical (O2-) into H2O2 using metals such as Cu, Fe, Mn, or Ni. H2O2 is then degraded to H2O by catalase
100%
what is the role of ion gradients in necrosis?it sets off a positive feedback loop of Na+ and Ca2+ entering the cell, opening voltage-gated channels, which lets more ions enter etc.
100%
what does this ion gradient cause that leads to necrosis?loss of volume control: water influx & cell swelling until the cell lyses (dies)
100%
what do dying cells do during necrosis?membrane integrity is lost and the cell body swells and bursts open
100%
microfilament dysfunction (disrupted morphology and function, impaired motility)
100%
mitochondrial Ca2+ uniporter
100%
what are oxidants?molecules that can accept an electron
100%
what are antioxidants?molecules that can donate an electron
100%
what affect will this have on neighbouring cells?none, the membrane makes it so cellular contents are not released, so cannot effect neighbouring cells
100%
what is necrosis?non-programmed cell death
100%
which is more reactive?oxidants
100%
oxidative stress
100%
what is lipid peroxidation?peroxidative degradation of lipids by removal of hydrogen from fatty acids, producing a lipid radical.
100%
physical damage to mitochondria (eg. chronic ethanol abuse)
100%
production of reaction oxygen and nitrogen species (leads to disintegration of membranes, proteins etc.)
100%
what is apoptosis?programmed cell death
100%
what causes oxidative stress?reactive oxygen (ROS) and reactive nitrogen (RNS) species
100%
which is most important?superoxide dismutase (SOD)
100%
what is narcosis?the bigger picture, downstream cellular effects that toxins can have
100%
how is this further broken down?this can be further broken down by reaction w oxygen, forming a lipid peroxyl radical
100%
what is oxidative stress?when the balance of oxidants and antioxidants is disrupted, meaning that more oxidants are present
100%

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