Exam 4: Metals I & II Flashcards
What role do metals play in biology?
Vital biochemical processes require energy inputs and catalysts. Cells evolved mechanisms to obtain required elements (metals), maintain them at physiological levels, and detoxify non-essential elements
Where are thiols found in biomolecules and why are they important in the mechanism of action of many metals and metalloids?
manly in cysteine, tripeptide glutathione. thiols are located within the active sites of many enzymes and acts as a catalysis.
What is metallothionein and what role does it play in the mammalian cell?
A ubiquitous, low molecular weight protein. MT can sequester heavy metals and prevent oxidation of critical protein or non-protein thiols.
What is the primary source for exposure to the metals/metalloids discussed in this lecture?
Emissions sources include mining, coal combustion, and volcanic eruptions
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?
The structure of cysteine-MeHg resembles the essential amino acid methionine
An amino acid transporter helps cysteine-MeHg cross the blood-brain barrier through “Molecular mimicry”
What effective treatments exist for cadmium toxicosis?
dunno. ethylenediaminetetraacetic acid (EDTA), British anti-Lewisite (BAL or dimercaprol), or dimercaptosuccinic acid (DMSA, or Succimer) have generally not proven effective
How do the different forms of arsenic differentially target metabolism and what is the selectivity of target tissues to arsenic toxicosis?
Arsenite (As+3) - Binds with lipoic acid (cofactor in the TCA cycle) thus effecting energy metabolism
Arsenate (As+5) - Uncouples oxidative phosphorylation because it competes with phosphate during conversion of ADP to ATP
Target tissues are those 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?
The foremost point source of lead poisoning in North American cattle appears to be lead-acid batteries found on agricultural pasture land
What treatment options are available for acute lead poisoning?
Remove Pb objects from GI tract
Ca-EDTA
Dimercaptosuccinic acid (DMSA, or Succimer)
What form of chromium is considered to contribute most to observed toxicosis?
Hexavalent chromium (CrVI/Cr6+) is a recognized carcinogen
What role does copper disposition play is susceptibility to copper toxicity and what role does genetics play in this process?
Inherited metabolic defect resulting in impaired biliary copper excretion
Gene responsible is COMMD1
Humans have a genetic pre-disposition to copper toxicity associated with mutations in ATP7B (Wilson disease)
What is the primary mechanism by which metals exert toxicosis? What clinical signs predominate for each of the metals?
What treatments are available for metal poisonings? How are they similar and how are they different for each metal?
What is the basis for the interaction of copper, molybdenum and sulfate in ruminants? What role does this play in potential toxicities?
Molybdenum and sulfur form thiomolybdate in the rumen and form an insoluble complex with copper. Therefore, adding molybdenum and sulfur to the diet of ruminants decreases copper availability.
How does iron “exist” in living systems?
Incorporated into many proteins where it plays a critical role:
Hemoglobin – binds O2 in the blood
Myoglobin – binds O2 in muscle
P450 enzymes – critical role in metabolism
Electron transport proteins in the mitochondria – energy formation
