Presented by Bennette King, Matt Segura, Matt Simmons, and
Sarah Matte
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This presentation will cover: Basic geologic and biological
implications of Arsenic Historical significance Natural and man
made sources Kinetics regarding absorption and excretion And the
mechanisms of action and the effects on body tissues and
organs.
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Arsenic is a naturally occurring silver metalloid Two main
types: organic and inorganic Accumulates in Earths crust: gets into
food and water sources Is also present in small concentrations in
the atmosphere. Image from: http://www.galleries.com/Arsenic
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Organic arsenic is a naturally present element in Earths crust,
mineral deposits, and local bedrock Due to many stable oxidative
states of organic arsenic, it can dwell in many minerals at
different pHs. Gold mining releases arsenic to the environment due
to the fact that they co-reside together in mineral deposits.
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Synthesized by laboratory means Has extremely long half-life Is
utilized in fertilizers Those fertilizers are then used to nourish
food crops. One crop that has extremely high concentrations of
inorganic arsenic is rice Water supplies that are used to hydrate
crops foster the absorption of water-soluble arsenic into the root,
and eventually the hulls of the rice grains during growth.
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http://www.sciencedirect.com/scienc
e/article/pii/S037842740200084X Arsenate being the more reactive
and toxic http://www.2the4.net/assets/images/MOLECUL E.GIF
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Inorganic arsenic is contaminating food sources through out the
world. Pesticide run off soaks into the rock layer where the water
table dwells, contaminating water sources as well as food. Arsenic,
both organic and inorganic forms, is toxic
http://students.cis.uab.edu/fauzia/arsenic1.jpg
http://3.bp.blogspot.com/_QdDgbVlfeAg/TAGA
Kc165nI/AAAAAAAAAZM/0_BczlPbaug/s1600/a rsenic-hands.jpg
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Arsenic has been used for years as Pesticide Chemotherapy agent
Treatment for eczema, psoriasis, malaria, and syphilis Homicidal
agent (poison)
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Arsenics toxic use really became popularized in the Middle Ages
Dubbed King of Poisons Used by Florences Medici Family to eradicate
rivals Arsenic was the element used to kill French Emperor Napoleon
Bonaparte Used by Madam LaFarge whose was charged with poisoning
her husband via arsenic cakes
http://farm9.staticflickr.com/8188/8127555423_a3082b0fda_z.jpg
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Arsenic, as a basic element, is toxic to most organic life by
itself, however it is extremely reactive and produces many chemical
species that are even more toxic, such as Arsine. Arsenic and its
derivatives are toxic by ingestion, injection (both subcutaneous
and intramuscular) and by inhalation of arsenic dust. The rate of
absorption via the respiratory tract is based on the size of the
particles and the ease that they cross over into the blood stream
due to solubility factors. Arsenic oxidizes readily when heated in
air, conditions easily found in labs or mining operations, and
produces toxic fumes that are very quickly absorbed within the
respiratory system. Arsenic is also able to enter the body via
dermal absorption, with different levels of effective absorption
based on chemical species of the arsenic compound. Arsine (AsH3)
image taken from: http://upload.wikimedia.org/wikipedia
/commons/4/44/Arsine.png
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Inorganic arsenic compounds are metabolized using two main
reaction types: These reactions process the arsenic into DMA and
MMA (mono- and di- methyl arsenic), which are easily processed in
the kidneys to the urine.
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Most inorganic arsenic is processed and eliminated via the
urine in most animal species via the kidneys. In adult males,
45-75% of ingested arsenic is reported to have been excreted in
urine within the first day to within a week. Fecal matter is also a
major route of excretion, as some arsenic material is never
absorbed in the gastro intestinal tract (different rates of
absorption between arsenic species is mainly determined by the
compounds solubility, with highly soluble molecules being absorbed
more readily) Sweat, to a very minor degree, as well as breast milk
in lactating females also play a very small role in excreting
arsenic. Arsenic tends to accumulate in keratin tissues, such as
hair, nails, and skin, isolating the compounds away from the blood
stream and serving as a containment/excreting system (to a very
small degree)
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Commonly ingested as Arsenobetaine, or fish arsenic, in humans
after eating any number of marine fish or crustaceans. Unlike
inorganic arsenic compounds, organic arsenicals are rapidly and
almost entirely absorbed via the gastrointestinal tract. Very
little data exists concerning the dermal or inhalation routes of
arsenic exposure, however laboratory animals have shown that
organic arsenic is also absorbed via these routes, although to a
much less degree. Images taken from:
http://steelturman.typepad.com/photos/uncategorized/arsenic_fish_carp_poison_war
ning.png
http://steelturman.typepad.com/photos/uncategorized/arsenic_fish_carp_poison_war
ning.png
http://www.undercurrentnews.com/2012/11/14/danish-shrimp-trawlers-on-enhanced-
control-in-russia/
http://upload.wikimedia.org/wikipedia/commons/thumb/a/a3/ArsenobetainePIC.svg/
160px-ArsenobetainePIC.svg.png
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Most organic arsenicals in the forms of MMA and DMA are
excreted as it, or processed by further methylation into DMA and
TMA (in limited amounts) to also be excreted via urine TMA is also
subjected to in vivo redox reactions to yield TMAO, which is
rapidly excreted out in urine. Additionally, some TMA is excreted
with exhaled air, but this amount is unquantified and under further
investigation. Arsenobetaine is excreted in urine normally, without
demethylation or any noted biotransformation. In fact, some other
organic arsenics are extensively processed to arsenobetaine to be
eliminated.
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It is metabolized by reduction/methylation, catalyzed by
glutathione-S- transferase omega-1 (GSTO1) and arsenic (III)
methyltransferase. GSTO1 reduces Arsenate Arsenite Arsenite is
detoxified by arsenic (III) methyltransferase (liver)
methylarsonate and dimethylarsinate
http://fc00.deviantart.net/fs43/i/2009/075/e/b/La
b_Rat_by_OralGiacomini.jpg
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ATP synthase is a multi-subunit, protein complex that catalyzes
the phosphorylation of ADP to ATP at the expense of a protons
generated by an electron transport chain in energy generating
membranes. Arsenate mimics the - phosphate of ATP. It inhibits ATP
synthesis at the active site of ATP synthase by competing with
phosphate. http://upload.wikimedia.org/wikipedia/comm
ons/thumb/0/00/Atp_synthase.PNG/300px- Atp_synthase.PNG
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Arsenate blocks the Pi H2O exchange and also the ATP Pi
exchange catalyzed by ATP. Thus arsenics binding to an ADP molecule
or competing with the gamma subunit of ATP will prevent cellular
respiration from occurring properly, resulting in energy loss and
possibly cell death. http://biochem.co/wp-
content/uploads/2010/02/glycolysi s-simple.png
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Leads to Chromosome aberration and defects.
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Conversion of pyruvate to acetyl CoA is used during tissue
respiration via: pyruvate dehydrogenase complex. Arsenic alters the
enzymes in this complex so that Acetyl CoA and CoASH do not
form.
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arsenate reacts with glucose and gluconate to form
glucose-6-arsenate and 6-arsenogluconate. These compounds resemble
glucose-6-phosphate and 6-phosphogluconate. Glucose-6-arsenate is a
substrate for glucose-6- phosphate dehydrogenase and can inhibit
hexokinase.
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The Janus kinase (JAK)-signal transducer and activator of
transcription (STAT) pathway is vital for facilitating normal
functions of different cytokines within the hematopoietic and
immune system.
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Sodium Arsenite directly inactivates the JAK tyrosine kinase
protein, thus inhibiting STAT 3 activation, which regulates
tyrosine phosphorylation. It activates map K activity How this
affects tissues is not completely known.
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Arsenic attacks at the cellular level in a very nonspecific way
Therefore every organ system is effected We'll cover the fun ones
Heart GI/Hepatic Reproductive Neurologic Renal
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Cardiogenic Shock Vascular permeability Cardiomyopathy
Hypertension (chronic exposure) Arsenic in gas form causes
Hemolysis evateuling.blogspot.c om
Encephelopathy Hepatic failure permeability (yet again)
Neuropathy Axon Destruction Pain/numbness to limbs Loss of
vision
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Acute Renal Failure Tubular necrosis perfusion due to
cardiovascular symptoms High As accumulations leads to cancers
www.osmonicwater.c om
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As easily crosses the Placenta Toxic to fetus 'Spontaneous'
abortions Tetrogenic effects (most fetuses don't make it to
birth)
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Hopefully this presentation provided you with more information
concerning this poisonous element, particularly in the areas of:
Natural sources and forms of Arsenic Historical use and
significance Kinetics concerning absorption and excretion
Metabolism The effects of arsenical compounds on the bodies tissues
and organs.
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Arsenic in your food. 11.2012. ConsumerReport.org. Arsenic.
Mechanics and Kinetics. April 16, 2013. Wikipedia: The Free
Encyclopedia. http://en.wikipedia.org/wiki/Arsenic. Arsenic:
Occupational Safety and Health Administration. 03.21.2012. OSHA.
Cheng H.Y., Li. P., David M., Smithgall T.E., Feng L. Lieberman
M.W. 2004. Arsenic inhibition of the JAK-STAT pathway. Nature
Publishing group: Oncogene. 23, 36033612. Hughes M.F. 2002. Arsenic
toxicity and potential mechanisms of action. Elsevier;Toxicology
Letters. Volume 133, Issue 1: 116. Pelicano H., Martin D.S., Xu
R-H., Huang P. 2006. Glycolysis inhibition for anticancer
treatment. Nature Publishing group: Oncogene. 25, 46334646.