Transcript Arsenic - UNM Biology

Presented by Bennette King, Matt Segura, Matt Simmons,
and Sarah Matte
 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.
 Arsenic is a naturally occurring silver metalloid
 Two main types: organic and inorganic
 Accumulates in Earth’s crust: gets into food and water
sources
 Is also present in small concentrations in the
atmosphere.
Image from: http://www.galleries.com/Arsenic
 Organic arsenic is a naturally present element in
Earth’s 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.
 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.
Arsenate being the more reactive and toxic
http://www.2the4.net/assets/images/MOLECUL
E.GIF
http://www.sciencedirect.com/scienc
e/article/pii/S037842740200084X
 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://3.bp.blogspot.com/_QdDgbVlfeAg/TAGA
Kc165nI/AAAAAAAAAZM/0_BczlPbaug/s1600/a
rsenic-hands.jpg
http://students.cis.uab.edu/fauzia/arsenic1.jpg
 Arsenic has been used for years as…
 Pesticide
 Chemotherapy agent
 Treatment for eczema, psoriasis, malaria, and syphilis
 Homicidal agent (poison)
 Arsenic’s toxic use really
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became popularized in the
Middle Ages
Dubbed “King of Poisons”
Used by Florence’s Medici
Family to eradicate rivals
Arsenic was the element used
to kill French Emperor
Napoleon Bonaparte
http://farm9.staticflickr.com/8188/8127555423_a3082b0fda_z.jpg
Used by Madam LaFarge
whose was charged with
poisoning her husband via
“arsenic cakes”
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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.
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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
 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.
 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)
 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://www.undercurrentnews.com/2012/11/14/danish-shrimp-trawlers-on-enhancedcontrol-in-russia/
http://upload.wikimedia.org/wikipedia/commons/thumb/a/a3/ArsenobetainePIC.svg/
160px-ArsenobetainePIC.svg.png
 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.
 It is metabolized by
reduction/methylation,
catalyzed by glutathione-Stransferase omega-1 (GSTO1) and
arsenic (III) methyltransferase.
 GSTO1 reduces Arsenate 
http://fc00.deviantart.net/fs43/i/2009/075/e/b/La
b_Rat_by_OralGiacomini.jpg
Arsenite
 Arsenite is detoxified by arsenic
(III) methyltransferase (liver) 
methylarsonate and
dimethylarsinate
 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 γphosphate 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/300pxAtp_synthase.PNG
 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/wpcontent/uploads/2010/02/glycolysi
s-simple.png
• Leads to Chromosome aberration and defects.
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.
 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-6phosphate dehydrogenase and can inhibit hexokinase.
 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.
 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
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Therefore every organ system is effected
We'll cover the fun ones
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Heart
GI/Hepatic
Reproductive
Neurologic
Renal
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Cardiogenic Shock
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↑ Vascular
permeability
Cardiomyopathy
Hypertension (chronic
exposure)
Arsenic in gas form causes
Hemolysis
evateuling.blogspot.c
om
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Hemorrhagic
Gastroenteritis
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↑Permeability
Hepatitis
Hepatic Necrosis
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acute exposures
medicaldictionary.thefreedictionary.com
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Encephelopathy
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Hepatic failure
↑permeability
(yet again)
Neuropathy
Axon Destruction
Pain/numbness to
limbs
Loss of vision
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Acute Renal Failure
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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
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Toxic to fetus
'Spontaneous' abortions
Tetrogenic effects (most fetuses don't make it to
birth)
 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.
 Arsenic in your food. 11.2012. ConsumerReport.org.
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<http:wwwmconsumereport.org/cro/magazine/2012/11/arsenicin-your-food/indexing>
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. <www.osha.gov/SLTC/arsenic/.>
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, 3603–3612.
Hughes M.F. 2002. Arsenic toxicity and potential mechanisms of
action. Elsevier;Toxicology Letters. Volume 133, Issue 1: 1–16.
Pelicano H., Martin D.S., Xu R-H., Huang P. 2006. Glycolysis
inhibition for anticancer treatment. Nature Publishing group:
Oncogene. 25, 4633–4646.