Arsenic Flashcards
what are a few uses for arsenic today
pesticides, herbicides, metal production, leukemia drug
where is arsenic found
naturally or can contaminate water and fish
what are 2 common forms of arsenic
trivalent (arsenite) and pentavalent (arsenate) forms
what happens to arsenate in the body
arsenate reductase turns it into arsenite
what happens to arsenite in the body
arsenite methyltransferase (AS3MT) turns it into MMA5+
what happens to MMA5+ in the body
arsenite methyltransferase (AS3MT) turns it into MMA3+
what happens to MMA3+ in the body
arsenite methyltransferase (AS3MT) turns it into DMA5+
what happens to DMA5+ in the body
arsenite methyltransferase (AS3MT) turns it into DMA3+
what happens to DMA3+ in the body
arsenite methyltransferase (AS3MT) turns it into TMAO
what is the order of compounds in arsenic breakdown (7)
arsenate arsenite MMA5+ MMA3+ DMA5+ DMA3+ TMAO
what is the order of toxicity of these compounds
arsenate arsenite MMA5+ MMA3+ DMA5+
MMA3+ >> arsenite > arsenate > MMA5+ = DMA5+
is TMAO toxic
no
is MMA5+ or MMA3+ more toxic
MMA3+ much more toxic
is arsenite or arsenate more toxic
arsenite
how is inorganic arsenic absorbed best + %
through GI 80-90%
how is inorganic arsenic absorbed inneficiently + %
through skin, but you can still get toxicity
what are 3 ways you can absorb arsenic
GI skin and inhalation
what type of arsenic is best absorbed via inhalation
arsene, trivalent arsenic oxide
where does arsenic concentrate
hair and fingernails
how much arsenic ingestion is fatal
70-180mg
what are symptoms of acute poisoning of arsenic (6)
fever, anorexia, hepatomegaly, cardiac arrhythmia, GI damage, sensory loss
what can acute poisoning of arsenic damage
mucous membranes of GI tract
what happens to sensory system with acute arsenic + how long
sensory loss 1-2 weeks after initial exposure but often reversible
what is a major target for chronic arsenic exposure
skin
what happens to skin with chronic arsenic exposure
pigmentation changes, hyperkeratosis, alopecia
what blood things happen with chronic arsenic exposure
bone marrow suppression, anemia
what happens to nerves with chronic arsenic exposure
symmetrical sensorimotor polyneuropathy (tingling and loss of sensation)
what is the classic symptom of chronic arsenic exposure
symmetrical sensorimotor polyneuropathy
what kind of cancers happen with chronic arsenic exposure
skin lung liver GI
what is the main mechanism of trivalent As toxicity
highly reactive with protein sulfhydryl groups
how does trivalent As react highly with protein sulfhydryl groups
interferes with pyruvate dehydrogenase complex so then acetylCoA formation is inhibited
what happens once trivalent As interferes with pyruvate dehydrogenase complex
acetylCoA formation from pyruvate is inhibited
what happens once trivalent As interrupts oxidative phosphorylation (2)
less ATP is formed so then ROS production
what happens with pentavalent forms of As (general)
it replaces phosphate
what is arsenolysis
arsenic ions replace phosphate in high energy compounds, so instead of ATP fomring you get ADP-arsenate
what happens with ATP levels in arsenolysis + result
they decrease, leading to cell death
how many enzymes can arsenic inhibit
over 200 diff ones
what kind of cell death does arsenic cause
induce MPT to cause apoptosis or necrosis
how does arsenic cause cancer + which type of arsenic mostly
trivalent species, alters DNA methylation and repair, chromosomal abnormalities
what do you use for cute arsenic poisoning
penicillamine or DMSA to chelate arsenic and promote renal excretion
what do you do for chronic arsenic poisoning
reduce exposure, maybe DMPS may help symptoms
does chelation help symptoms of chronic arsenic exposure
no evidence that it will