6 metals and metalloids II Flashcards
what are the cellular metal detoxification pathways?
why are free ion metals the most toxic?
-most reactive, so will bind to proteins, membranes, etc
MT=metallothioneins
-have many thiols (-SH) and have alot of cysteine (which also has sulfur)
-sulfur has very high affinity for metal ions
-when metals bind, they are no longer in their free ion form
GSH=glutathione
-has lots of sulfur, also binds to free ions
MRG= metal reach granules
all defense mechanisms are highly energetically expensive and can be saturated
what is the graph of the detoxification of metals (granules)?
-type A: can store and accumulate metals bound to MT
-type B: want oxygens, also stored
-type C: specific pathways, transferrin and ferritin are different types of MRGs
what was the case-study of woodlice (oniscus asellus)?
looked at hepatopancreatic cells
-all dots are metal reach granules that are accumulated with metal ions
-invertebrates are very good with metals
what is the spill-over hypothesis of metal toxicity?
BIM
-energetically expensive
-have limits, so can get saturated which leads to spill-over of free metal ions (free to bind)
BAM
-free metal ions will bind to
what are the modes of toxic action?
-alteration of sub-cellular and membrane bound enzyme/protein activities
-generation of toxic reactive oxygen species (ROS)
what is the alteration of sub-cellular and membrane bound enzyme/protein activities?
mode of toxic action
-binding to the active site
-displacing the metal physiologically associated with enzyme molecules
these processes could result in inhibition or inactivation of the enzymes
what is the generation of a toxic reaction oxygen species (ROS)?
toxic mode of action
-some metals (e.g. Fe, Cu, Cr) greatly accelerates ROS generation
-a few metals (e.g. Cd, Hg) depletes ROS scavenging proteins in the cell, and thus allows greater ROS mediated damage
what is the graph of the overwhelming antioxidant machinery?
what are the sources of cadmium?
-natural sources: rock and soils
-Canada produces 1500 tonnes/yr
-by-product of lead/zinc mining
-nickel-cadmium batteries
-electroplating and galvanizing
-cigarette smoke: major source to humans
what is the chemistry and kinetics of cadmium?
-Cd2+ is readily taken up by organisms
-sequestration occurs primarily in kidney and liver
-major storage organ is the kidney
-very high biological residence time (e.g. 10-33 yrs in humans)
what is the mechanism of action of cadmium?
-binds to -SH proteins with very high affinity causing enzyme dysfunction, and depletion of metal chelating (e.g. metallothioneins) and ROS scavenging proteins (e.g. glutathione)
-disrupts calcium regulation in animal systems
what are the effects of cadmium?
-hypocalcemia in aquatic animals
-deposition in bones causing osteomalacia and osteoporosis (bone weakness) in vertebrates
-itai-itai disease in humans
-immuno-suppression and endocrine disruption
-lung irritation, emphysema if inhaled
-kidney damage is a sensitive marker of Cd toxicity
what are the water quality guidelines in Canada of Cadmium?
what are the soil quality guidelines for land use in canada of cadmium?
how has cadmium affected hares?
-the femoral neck shows osteoporotic changes- whereas the metaphysis shows longitudinally sclerosed trabeculae
-the inferior femur shows profound osteoporosis
-severe osteoporosis of the transverse process