Editing Arsenic (section)

== Biological role ==
{{Main|Arsenic biochemistry}}

=== Bacteria ===
Some species of bacteria obtain their energy in the absence of oxygen by [[redox|oxidizing]] various fuels while [[redox|reducing]] arsenate to arsenite. Under oxidative environmental conditions some bacteria use arsenite as fuel, which they oxidize to arsenate.<ref>{{cite journal|last1 = Stolz|first1 = John F.|last2 = Basu|first2 = Partha|last3 = Santini|first3 = Joanne M.|last4 = Oremland|first4 = Ronald S.|s2cid = 2575554|title = Arsenic and Selenium in Microbial Metabolism|journal = Annual Review of Microbiology|volume = 60|pages = 107–130|date = 2006|doi = 10.1146/annurev.micro.60.080805.142053|pmid=16704340| bibcode=2006ARvMb..60..107S }}</ref> The [[enzyme]]s involved are known as [[Arsenate reductase (glutaredoxin)|arsenate reductases]] (Arr).<ref>{{cite journal |doi = 10.1111/j.1574-6976.2002.tb00617.x |title = Microbial arsenic: From geocycles to genes and enzymes |date = 2002 |last1 = Mukhopadhyay |first1 = Rita |last2 = Rosen |first2 = Barry P. |last3 = Phung |first3 = Le T. |last4 = Silver |first4 = Simon |journal = FEMS Microbiology Reviews |volume = 26 |issue = 3 |pages = 311–325 |pmid = 12165430| doi-access = free }}</ref>

In 2008, bacteria were discovered that employ a version of [[photosynthesis]] in the absence of oxygen with arsenites as [[electron donor]]s, producing arsenates (just as ordinary photosynthesis uses water as electron donor, producing molecular oxygen). Researchers conjecture that, over the course of history, these photosynthesizing organisms produced the arsenates that allowed the arsenate-reducing bacteria to thrive. One [[strain (biology)|strain]], PHS-1, has been isolated and is related to the [[gammaproteobacterium]] ''[[Ectothiorhodospira shaposhnikovii]]''. The mechanism is unknown, but an encoded Arr enzyme may function in reverse to its known [[homology (biology)|homologues]].<ref>{{cite journal |last1=Kulp |first1=T.R |last2= Hoeft |first2= S.E. |last3= Asao |first3= M. |last4= Madigan |first4= M.T. |last5= Hollibaugh |first5= J.T. |last6= Fisher |first6= J.C. |last7= Stolz |first7= J.F. |last8= Culbertson |first8= C.W. |last9= Miller |first9= L.G.|first10=R.S. |last10=Oremland |display-authors=6 |year = 2008 |title = Arsenic(III) fuels anoxygenic photosynthesis in hot spring biofilms from Mono Lake, California|journal = [[Science (journal)|Science]]|volume = 321 |issue = 5891|pages = 967–970|doi = 10.1126/science.1160799 |pmid= 18703741 |s2cid = 39479754|bibcode = 2008Sci...321..967K}}
:
{{cite magazine |first=Fred |last=Campbell |date=11 August 2008 |title=Arsenic-loving bacteria rewrite photosynthesis rules |magazine=Chemistry World |url=https://www.chemistryworld.com/news/arsenic-loving-bacteria-rewrite-photosynthesis-rules/3000398.article }}</ref>

In 2010, researchers reported the discovery of a strain of the bacterium ''[[Halomonas]]'' (designated GFAJ-1) that was allegedly capable of substituting arsenic for phosphorus in its biomolecules, including DNA, when grown in an arsenic-rich, phosphate-limited environment. This claim, published in ''Science'', suggested that arsenic could potentially serve as a building block of life in place of phosphorus, challenging long-standing assumptions about biochemical requirements for life on Earth.<ref>{{Cite journal |last1=Wolfe-Simon |first1=Felisa |last2=Blum |first2=Jodi Switzer |last3=Kulp |first3=Thomas R. |last4=Gordon |first4=Gwyneth W. |last5=Hoeft |first5=Shelley E. |last6=Pett-Ridge |first6=Jennifer |last7=Stolz |first7=John F. |last8=Webb |first8=Samuel M. |last9=Weber |first9=Peter K. |last10=Davies |first10=Paul C. W. |last11=Anbar |first11=Ariel D. |last12=Oremland |first12=Ronald S. |date=2011-06-03 |title=A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus |url=https://www.science.org/doi/10.1126/science.1197258 |journal=Science |volume=332 |issue=6034 |pages=1163–1166 |doi=10.1126/science.1197258|pmid=21127214 |bibcode=2011Sci...332.1163W }}</ref>

The claim was met with widespread skepticism. Subsequent studies provided evidence contradicting the initial findings. One follow-up study published in ''Science'' in 2011 demonstrated that GFAJ-1 still requires phosphate to grow and does not incorporate arsenate into its DNA in any biologically significant way.<ref>{{Cite journal |last1=Cotner |first1=James B. |last2=Hall |first2=Edward K. |date=2011-06-03 |title=Comment on "A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus" |url=https://www.science.org/doi/10.1126/science.1201943 |journal=Science |volume=332 |issue=6034 |pages=1149 |doi=10.1126/science.1201943|pmid=21622705 |bibcode=2011Sci...332R1149C }}</ref> Another independent investigation in 2012 used more sensitive techniques to purify and analyze the DNA of GFAJ-1 and found no detectable arsenate incorporated into the DNA backbone. The authors concluded that the original observations were likely due to experimental contamination or insufficient purification methods.<ref>{{Cite journal |last1=Erb |first1=Tobias J. |last2=Kiefer |first2=Patrick |last3=Hattendorf |first3=Bodo |last4=Günther |first4=Detlef |last5=Vorholt |first5=Julia A. |date=2012-07-27 |title=GFAJ-1 Is an Arsenate-Resistant, Phosphate-Dependent Organism |url=https://www.science.org/doi/10.1126/science.1218455 |journal=Science |volume=337 |issue=6093 |pages=467–470 |doi=10.1126/science.1218455|pmid=22773139 |bibcode=2012Sci...337..467E }}</ref> Together, these studies reaffirmed phosphorus as an essential element for all known forms of life.

=== Potential role in higher animals ===

Arsenic may be an essential trace mineral in birds, involved in the synthesis of methionine metabolites.<ref>{{cite journal |last1=Živkov Baloš |first1=M. |last2=Jakšić |first2=S. |last3=Ljubojević Pelić |first3=D. |date=September 2019 |title=The role, importance and toxicity of arsenic in poultry nutrition |journal=World's Poultry Science Journal |volume=75 |issue=3 |pages=375–386 |doi=10.1017/S0043933919000394 }}</ref> However, the role of arsenic in bird nutrition is disputed, as other authors state that arsenic is toxic in small amounts.<ref>{{cite journal | last = Aljohani | first = A.S. | year = 2023 | title=Heavy metal toxicity in poultry: A comprehensive review | journal=Frontiers in Veterinary Science | volume=10 | pmid=37456954 | pmc=10340091 | doi=10.3389/fvets.2023.1161354 | doi-access=free }}</ref>

Some evidence indicates that arsenic is an essential trace mineral in mammals.<ref name=ANut>Anke M. (1986) "Arsenic", pp. 347–372 in Mertz W. (ed.), ''Trace elements in human and Animal Nutrition'', 5th ed. Orlando, FL: Academic Press</ref><ref name=UEssent>
{{cite journal
 |last1=Uthus |first1=Eric O.
 |year=1992
 |title= Evidency for arsenical essentiality
 |journal= Environmental Geochemistry and Health 
 |volume=14 |issue=2 |pages=55–58
 |pmid=24197927  |bibcode=1992EnvGH..14...55U
 |s2cid=22882255 |doi=10.1007/BF01783629
}}
:
{{cite book
 |last=Uthus |first=E.O.
 |year=1994
 |section=Arsenic essentiality and factors affecting its importance
 |editor1-last=Chappell  |editor1-first=W.R.
 |editor2-last=Abernathy |editor2-first=C.O.
 |editor3-last=Cothern   |editor3-first=C.R.
 |title=Arsenic Exposure and Health
 |pages=199–208
 |place=Northwood, UK
 |publisher=Science and Technology Letters
}}
</ref>

Experimental studies in rodents and livestock have shown that arsenic deprivation can lead to impaired growth, reduced reproductive performance, and abnormal glucose metabolism, suggesting it may play a role in essential metabolic processes.<ref>{{Cite book |url=https://nap.nationalacademies.org/catalog/6444/arsenic-in-drinking-water |title=Arsenic in Drinking Water |date=1999-06-14 |publisher=National Academies Press |isbn=978-0-309-06333-3 |location=Washington, D.C.|doi=10.17226/6444 |pmid=25101451 |author1=National Research Council (US) Subcommittee on Arsenic in Drinking Water }}</ref> Arsenic has been proposed to participate in [[methylation]] reactions, possibly influencing gene regulation and detoxification pathways.<ref>{{Cite journal |last1=Abernathy |first1=C O |last2=Liu |first2=Y P |last3=Longfellow |first3=D |last4=Aposhian |first4=H V |last5=Beck |first5=B |last6=Fowler |first6=B |last7=Goyer |first7=R |last8=Menzer |first8=R |last9=Rossman |first9=T |last10=Thompson |first10=C |last11=Waalkes |first11=M |date=July 1999 |title=Arsenic: health effects, mechanisms of actions, and research issues. |journal=Environmental Health Perspectives |volume=107 |issue=7 |pages=593–597 |doi=10.1289/ehp.99107593 |pmc=1566656 |pmid=10379007|bibcode=1999EnvHP.107..593A }}</ref> However, because the threshold between beneficial and toxic exposure is extremely narrow, arsenic is not currently classified as an essential element for humans, and its physiological role in higher animals remains uncertain.<ref>{{Cite journal |last=Hughes |first=Michael F. |date=2002-07-07 |title=Arsenic toxicity and potential mechanisms of action |url=https://pubmed.ncbi.nlm.nih.gov/12076506 |journal=Toxicology Letters |volume=133 |issue=1 |pages=1–16 |doi=10.1016/s0378-4274(02)00084-x |issn=0378-4274 |pmid=12076506}}</ref>

=== Heredity ===

Arsenic has been linked to [[epigenetics|epigenetic changes]], heritable changes in gene expression that occur without changes in [[DNA sequence]]. These include DNA methylation, histone modification, and [[RNA]] interference. Toxic levels of arsenic cause significant DNA hypermethylation of tumor suppressor genes [[p16 (gene)|p16]] and [[p53]], thus increasing risk of [[carcinogenesis]]. These epigenetic events have been studied ''in vitro'' using human [[kidney]] cells and ''in vivo'' using rat [[liver]] cells and peripheral blood [[leukocytes]] in humans.<ref>{{cite journal|last1=Baccarelli|first1=A.|date=2009|title=Epigenetics and environmental chemicals|journal=Current Opinion in Pediatrics |issue=2 |volume=21 |pages=243–251 |doi=10.1097/MOP.0b013e32832925cc |pmid=19663042|last2=Bollati|first2=V.|pmc=3035853}}</ref> [[Inductively coupled plasma mass spectrometry]] (ICP-MS) is used to detect precise levels of intracellular arsenic and other arsenic bases involved in epigenetic modification of DNA.<ref>{{cite journal|last1=Nicholis|first1=I.|date=2009|title=Arsenite medicinal use, metabolism, pharmacokinetics and monitoring in human hair| journal=Biochimie| pmid=19527769| doi=10.1016/j.biochi.2009.06.003 |last2=Curis |last3=Deschamps|last4=Bénazeth|volume=91|first2=E.|first3=P.|first4=S.|issue=10|pages=1260–1267}}</ref> Studies investigating arsenic as an epigenetic factor can be used to develop precise biomarkers of exposure and susceptibility.

The Chinese brake fern (''[[Pteris vittata]]'') hyperaccumulates arsenic from the soil into its leaves and has a proposed use in [[phytoremediation]].<ref>{{Cite journal
| volume = 156
| journal = New Phytologist
| title = Arsenic Distribution and Speciation in the Fronds of the Hyperaccumulator Pteris vittata
| issue = 2
| pages = 195–203
| jstor = 1514012
| doi = 10.1046/j.1469-8137.2002.00512.x
| year = 2002 |first5 = S. P.
| last5 = McGrath
 |first2 = F.-J.
| last2 = Zhao
| first1 = E.
| last3 = Fuhrmann |first3 = M. |first4 = L. Q.
| last4 = Ma
| last1 = Lombi
| pmid = 33873285
| doi-access = free
| bibcode = 2002NewPh.156..195L
}}
</ref>

=== Biomethylation ===
[[File:ArsenobetainePIC.svg|thumb|[[Arsenobetaine]]]]

Inorganic arsenic and its compounds, upon entering the [[food chain]], are progressively metabolized through a process of [[methylation]].<ref name="Biomethylation">{{cite journal|title = Biomethylation of Arsenic is Essentially Detoxicating Event|journal = Journal of Health Science|date = 2003|first1 = Teruaki Sakurai|volume = 49|issue = 3|pages = 171–178| doi = 10.1248/jhs.49.171|last1 = Sakurai|doi-access = free}}</ref><ref>{{cite book|last=Reimer|first=K. J.|author2=Koch, I.|author3=Cullen, W.R.|date=2010|title=Organoarsenicals. Distribution and transformation in the environment|volume=7 |pages=165–229|isbn=978-1-84755-177-1|pmid=20877808|doi=10.1039/9781849730822-00165|series=Metal Ions in Life Sciences}}</ref> For example, the mold ''[[Scopulariopsis brevicaulis]]'' produces [[trimethylarsine]] if inorganic arsenic is present.<ref>{{cite journal |first1 = Ronald |last1 = Bentley |last2 = Chasteen |first2 = T.G. |year = 2002 |title = Microbial methylation of metalloids: Arsenic, antimony, and bismuth |journal = Microbiology and Molecular Biology Reviews |volume = 66 |issue = 2 |pages = 250–271 |doi = 10.1128/MMBR.66.2.250-271.2002 |pmid = 12040126 |pmc = 120786}}</ref> The organic compound [[arsenobetaine]] is found in some marine foods such as fish and algae, and also in mushrooms in larger concentrations. The average person's intake is about 10–50&nbsp;μg/day. Values about 1000&nbsp;μg are not unusual following consumption of fish or mushrooms, but there is little danger in eating fish because this arsenic compound is nearly non-toxic.<ref>{{cite journal |first1 = William R. |last1 = Cullen |last2 = Reimer |first2 = Kenneth J. |year = 1989 | title = Arsenic speciation in the environment |journal = Chemical Reviews |volume = 89|issue = 4|pages =713–764|doi = 10.1021/cr00094a002 |hdl = 10214/2162|hdl-access = free}}</ref>