Exam 4 - Metals Flashcards
What role do metals play in biology?
Vital biochemical processes require energy inputs and catalysts
Where are thiols found in biomolecules and why are they important in the mechanism of action of many metals and metalloids?
Thiols are present on cysteine, tripeptide glutathione, and cysteine residues of proteins & enzymes
located within the active sites of many enzymes and directly involved in catalysis
they are molecular targets of class B and intermediate elements
What is metallothionein and what role does it play in the mammalian cell?
metal binding protein - detoxifies metals
1 molecule can bind 7 Cd & other metals
sequesters heavy metals and prevents oxidation of critical protein or nonprotein thiols
What “form” of mercury is considered the most significant with regards to toxicity and what specifically about the molecular makeup allows it to access the CNS?
methyl mercury MeHg
resembles amino acid methionine so amino acid transporter helps cysteine-MeHg cross the BBB through “molecular mimicry”
Mercury toxicity treatment
DMSA/succimer
exposure to Cadmium
sewer sludge pastures with cattle
what metal toxicities are enhanced by a Calcium deficiency
Cadmium
Lead
what does Cadmium replace at binding sites and what can this result in
replaces Cu & Zn
Cu deficiency
What effective treatments exist for cadmium toxicosis?
minimize/reduce exposure
EDTA
NO BAL - increase nephrotoxicity
NO DMSA/succimer - ineffective
How do the different forms of arsenic differentially target metabolism
As3+ binds lipoic acid (in TCA cycle) affecting energy metabolism
As5+ uncouples oxidative phosphorylation
what is the common exposure of arsenic toxicity
contaminated ashes or water in cattle
what is the selectivity of target tissues to arsenic toxicosis?
targets tissues with high oxidative energy use (actively dividing cells) – intestinal epithelium, liver, kidney, spleen, epidermis
What is the most likely source of lead poisoning in cattle in North America?
Lead-acid batteries found on pasture
what metal has the greatest frequency of toxicosis and in what species
lead - primarily dogs & cattle
What treatment options are available for acute lead poisoning?
Remove lead objects from GI tract
Ca-EDTA
DMA/Succimer
What form of chromium is considered to contribute most to observed toxicosis?
Cr6+/CrVI is responsible for toxicity
exposure to Chromium for toxicosis
cattle exposed to oil sludge or drip + dermal contamination
What role does copper disposition play in susceptibility to copper toxicity
Normally [Cu] in the cell are kept low through Cu-binding proteins, but when too high the “free Cu ions” undergo redox rxn forming ROS
it can also accumulate in the liver = hepatotoxicity
what role does genetics play in Cu toxicity
Dogs with inherited/genetic metabolic defects impair biliary Cu excretion
bedlington terriers - COMMD1 gene
doberman pinscher - ATP7A & 7B mutation
Labs ATP7B polymorphism and RETN mutations
clinical signs of Mercury toxicity
MeHg - neurologic
inorganic - GI & kidney
elemental Hg0 - kidney
clinical signs of Cadmium toxicity
diffuse signs (aggression, anxiety, GI disturbance, mild anemia)
clinical signs of Arsenic toxicity
sudden death, diarrhea, ataxia, dehydration, resp distress
clinical signs of Lead toxicity
sudden blindness, aggression, head pressing, circling, roaring, anorexia, anemia, tonic-clonic epileptic seizures
clinical signs of Chromium toxicity
inflam/damage to GI, kidney, liver, gastroenteritis, dermatitis
