Editing Carbon monoxide (section)

==Biological and physiological properties==

===Physiology===
{{Main|Gasotransmitter}}

{{see also|Carboxyhemoglobin}}
Carbon monoxide is a bioactive molecule which acts as a [[Gaseous signaling molecules|gaseous signaling molecule]]. It is naturally produced by many enzymatic and non-enzymatic pathways,<ref name="Hopper-2020" /> the best understood of which is the catabolic action of [[heme oxygenase]] on the [[heme]] derived from [[hemoprotein]]s such as [[hemoglobin]].<ref>{{Cite journal|last1=Ryter|first1=Stefan W.|last2=Alam|first2=Jawed|last3=Choi|first3=Augustine M. K.|date=2006-04-01|title=Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications|url=https://journals.physiology.org/doi/full/10.1152/physrev.00011.2005|journal=Physiological Reviews|volume=86|issue=2|pages=583–650|doi=10.1152/physrev.00011.2005|pmid=16601269|issn=0031-9333}}</ref> Following the first report that carbon monoxide is a normal neurotransmitter in 1993,<ref name="Hopper2021" /> carbon monoxide has received significant clinical attention as a biological regulator.

Because of carbon monoxide's role in the body, abnormalities in its metabolism have been linked to a variety of diseases, including neurodegenerations, hypertension, heart failure, and pathological inflammation.<ref name="endogenous_co">{{Cite journal|last1=Wu|first1=L|last2=Wang|first2=R|date=December 2005|title=Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications|journal=Pharmacol Rev|volume=57|issue=4|pages=585–630|doi=10.1124/pr.57.4.3|pmid=16382109|s2cid=17538129}}</ref> In many tissues, carbon monoxide acts as [[anti-inflammatories|anti-inflammatory]], [[vasodilators|vasodilatory]], and encouragers of [[neovascular]] growth.<ref>{{Cite journal|last1=Campbell|first1=Nicole K.|last2=Fitzgerald|first2=Hannah K.|last3=Dunne|first3=Aisling|date=2021-01-29|title=Regulation of inflammation by the antioxidant haem oxygenase 1|url=https://www.nature.com/articles/s41577-020-00491-x|journal=Nature Reviews Immunology|volume=21|issue=7|language=en|pages=411–425|doi=10.1038/s41577-020-00491-x|pmid=33514947|s2cid=231762031|issn=1474-1741}}</ref> In animal model studies, carbon monoxide reduced the severity of experimentally induced bacterial [[sepsis]], pancreatitis, hepatic [[ischemia/reperfusion injury]], colitis, osteoarthritis, lung injury, lung transplantation rejection, and neuropathic pain while promoting skin wound healing. Therefore, there is significant interest in the therapeutic potential of carbon monoxide becoming pharmaceutical agent and clinical standard of care.<ref name="Motterlini-2010">{{Cite journal|last1=Motterlini|first1=Roberto|last2=Otterbein|first2=Leo E.|date=2010|title=The therapeutic potential of carbon monoxide|url=https://www.nature.com/articles/nrd3228|journal=Nature Reviews Drug Discovery|language=en|volume=9|issue=9|pages=728–743|doi=10.1038/nrd3228|pmid=20811383|s2cid=205477130|issn=1474-1784}}</ref>

====Medicine====
{{Main|Carbon monoxide-releasing molecules}}

Studies involving carbon monoxide have been conducted in many laboratories throughout the world for its anti-inflammatory and cytoprotective properties.<ref>{{Cite journal|last1=Motterlini|first1=Roberto|last2=Foresti|first2=Roberta|date=2017-01-11|title=Biological signaling by carbon monoxide and carbon monoxide-releasing molecules|journal=American Journal of Physiology. Cell Physiology|volume=312|issue=3|pages=C302–C313|doi=10.1152/ajpcell.00360.2016|pmid=28077358|issn=0363-6143|doi-access=free}}</ref> These properties have the potential to be used to prevent the development of a series of pathological conditions including ischemia reperfusion injury, transplant rejection, atherosclerosis, severe sepsis, severe malaria, or autoimmunity.<ref name="Motterlini-2010" /> Many pharmaceutical drug delivery initiatives have developed methods to safely administer carbon monoxide, and subsequent controlled clinical trials have evaluated the therapeutic effect of carbon monoxide.<ref>{{Cite journal|last1=Hopper|first1=Christopher P.|last2=Meinel|first2=Lorenz|last3=Steiger|first3=Christoph|last4=Otterbein|first4=Leo E.|date=2018-10-11|title=Where is the Clinical Breakthrough of Heme Oxygenase-1 / Carbon Monoxide Therapeutics?|url=https://www.eurekaselect.com/164002/article|journal=Current Pharmaceutical Design|language=en|volume=24|issue=20|pages=2264–2282|doi=10.2174/1381612824666180723161811|pmid=30039755|s2cid=51712930}}</ref>

===Microbiology===
Microbiota may also utilize carbon monoxide as a [[gasotransmitter]].<ref>{{Cite journal|last1=Wareham|first1=Lauren K.|last2=Southam|first2=Hannah M.|last3=Poole|first3=Robert K.|date=2018-09-06|title=Do nitric oxide, carbon monoxide and hydrogen sulfide really qualify as 'gasotransmitters' in bacteria?|url= |journal=Biochemical Society Transactions|volume=46|issue=5|pages=1107–1118|doi=10.1042/BST20170311|pmid=30190328|pmc=6195638|issn=0300-5127}}</ref> Carbon monoxide sensing is a signaling pathway facilitated by proteins such as [[CooA]].<ref>{{Cite journal|author1=Roberts, G. P. |author2=Youn, H. |author3=Kerby, R. L. |title=CO-Sensing Mechanisms|journal=Microbiology and Molecular Biology Reviews|year=2004|volume=68|pages=453–473|doi=10.1128/MMBR.68.3.453-473.2004|pmid=15353565|issue=3|pmc=515253}}</ref><ref>{{Cite journal|last1=Shimizu|first1=Toru|last2=Lengalova|first2=Alzbeta|last3=Martínek|first3=Václav|last4=Martínková|first4=Markéta|date=2019-12-09|title=Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres|url=https://pubs.rsc.org/en/content/articlelanding/2019/cs/c9cs00268e|journal=Chemical Society Reviews|language=en|volume=48|issue=24|pages=5624–5657|doi=10.1039/C9CS00268E|pmid=31748766|s2cid=208217502|issn=1460-4744}}</ref><ref>{{Cite journal|last1=Shimizu|first1=Toru|last2=Huang|first2=Dongyang|last3=Yan|first3=Fang|last4=Stranava|first4=Martin|last5=Bartosova|first5=Martina|last6=Fojtíková|first6=Veronika|last7=Martínková|first7=Markéta|date=2015-07-08|title=Gaseous O2, NO, and CO in Signal Transduction: Structure and Function Relationships of Heme-Based Gas Sensors and Heme-Redox Sensors|url=https://doi.org/10.1021/acs.chemrev.5b00018|journal=Chemical Reviews|volume=115|issue=13|pages=6491–6533|doi=10.1021/acs.chemrev.5b00018|pmid=26021768|issn=0009-2665}}</ref> The scope of the biological roles for carbon monoxide sensing is still unknown.

The human microbiome produces, consumes, and responds to carbon monoxide.<ref name="Hopper-2020">{{Cite journal|last1=Hopper|first1=Christopher P.|last2=De La Cruz|first2=Ladie Kimberly|last3=Lyles|first3=Kristin V.|last4=Wareham|first4=Lauren K.|last5=Gilbert|first5=Jack A.|last6=Eichenbaum|first6=Zehava|last7=Magierowski|first7=Marcin|last8=Poole|first8=Robert K.|last9=Wollborn|first9=Jakob|last10=Wang|first10=Binghe|date=2020-12-23|title=Role of Carbon Monoxide in Host–Gut Microbiome Communication|url=https://doi.org/10.1021/acs.chemrev.0c00586|journal=Chemical Reviews|volume=120|issue=24|pages=13273–13311|doi=10.1021/acs.chemrev.0c00586|pmid=33089988|s2cid=224824871|issn=0009-2665}}</ref> For example, in certain bacteria, carbon monoxide is produced via the [[redox|reduction]] of carbon dioxide by the enzyme [[carbon monoxide dehydrogenase]] with favorable [[bioenergetics]] to power downstream cellular operations.<ref>{{Cite book|title=Bioorganometallics: Biomolecules, Labeling, Medicine|editor=Jaouen, G.|publisher=Wiley-VCH|location=Weinheim|year=2006|isbn=978-3-527-30990-0}}</ref><ref name="Hopper-2020" /> In another example, carbon monoxide is a nutrient for [[methanogen]]ic archaea which reduce it to methane using hydrogen.<ref>{{Cite journal|author=Thauer, R. K. |title=Biochemistry of methanogenesis: a tribute to Marjory Stephenson. 1998 Marjory Stephenson Prize Lecture|year=1998|journal=[[Microbiology (journal)|Microbiology]]|volume=144|issue=9|pages=2377–2406|url=http://mic.microbiologyresearch.org/deliver/fulltext/micro/144/9/mic-144-9-2377.pdf?itemId=/content/journal/micro/10.1099/00221287-144-9-2377|format=Free|doi=10.1099/00221287-144-9-2377|pmid=9782487|doi-access=free}}</ref>

Carbon monoxide has certain antimicrobial properties which have been studied to treat against infectious diseases.<ref name="Hopper-2020" />

====Food science====
Carbon monoxide is used in [[modified atmosphere]] packaging systems in the US, mainly with fresh meat products such as beef, pork, and fish to keep them looking fresh. The benefit is two-fold: carbon monoxide protects against microbial spoilage and it enhances the meat color for consumer appeal.<ref name="Van Rooyen">{{Cite journal|last1=Van Rooyen|first1=Lauren Anne|last2=Allen|first2=Paul|last3=O'Connor|first3=David I.|date=October 2017|title=The application of carbon monoxide in meat packaging needs to be re-evaluated within the EU: An overview|journal=Meat Science|language=en|volume=132|pages=179–188|doi=10.1016/j.meatsci.2017.03.016|pmid=28465017|doi-access=free}}</ref> The carbon monoxide combines with [[myoglobin]] to form carboxymyoglobin, a bright-cherry-red pigment. Carboxymyoglobin is more stable than the oxygenated form of myoglobin, oxymyoglobin, which can become oxidized to the brown pigment [[metmyoglobin]]. This stable red color can persist much longer than in normally packaged meat. Typical levels of carbon monoxide used in the facilities that use this process are between 0.4% and 0.5%.<ref name="Van Rooyen" />

The technology was first given "[[generally recognized as safe]]" (GRAS) status by the [[U.S. Food and Drug Administration]] (FDA) in 2002 for use as a secondary packaging system, and does not require labeling. In 2004, the FDA approved CO as primary packaging method, declaring that CO does not mask spoilage odor.<ref name="Meatsci2005_eilert">{{Cite journal|author=Eilert EJ|year=2005|title=New packaging technologies for the 21st century|journal=Journal of Meat Science|volume=71|issue=1|pages=122–127|doi=10.1016/j.meatsci.2005.04.003|pmid=22064057}}</ref> The process is currently unauthorized in many other countries, including Japan, [[Singapore]], and the [[European Union]].<ref>{{Cite news|date=November 14, 2007|title=Proof in the Pink? Meat Treated to Give It Fresh Look|agency=ABC News|url=https://abcnews.go.com/GMA/Consumer/Story?id=3863064&page=1|access-date=May 5, 2009}}</ref><ref>{{Cite book|url=http://www.meatami.com/ht/a/GetDocumentAction/i/40141|title=Carbon Monoxide in Meat Packaging: Myths and Facts|publisher=American Meat Institute|year=2008|access-date=May 5, 2009|archive-url=https://web.archive.org/web/20110714064101/http://www.meatami.com/ht/a/GetDocumentAction/i/40141|archive-date=2011-07-14|url-status=dead}}</ref><ref>{{Cite web|title=CO in packaged meat|url=http://www.carbonmonoxidekills.com/packages_meat.htm|url-status=dead|archive-url=https://web.archive.org/web/20100926055707/http://www.carbonmonoxidekills.com/packages_meat.htm|archive-date=September 26, 2010|access-date=May 5, 2009|publisher=Carbon Monoxide Kills Campaign}}</ref>

=== Weaponization ===
In ancient history, [[Hannibal]] executed [[Ancient Rome|Roman]] prisoners with coal fumes during the [[Second Punic War]].<ref name="Hopper2021" />

Carbon monoxide had been used for [[genocide]] during [[the Holocaust]] at some [[Extermination camps in the Holocaust|extermination camps]], the most notable by [[Nazi gas van|gas van]]s in [[Chełmno extermination camp|Chełmno]], and in the [[Action T4]] "[[euthanasia]]" program.<ref>{{Cite book|author=Kitchen, Martin|url=https://books.google.com/books?id=_04R6DoPxLoC&pg=PT323|title=A history of modern Germany, 1800–2000|publisher=Wiley-Blackwell|year=2006|isbn=978-1-4051-0041-0|page=323}}</ref>