Editing Propionic acid (section)

==Biology==
Propionic acid is produced biologically as its coenzyme A ester, [[propionyl-CoA]], from the [[metabolism|metabolic]] breakdown of fatty acids containing [[odd number]]s of [[carbon]] atoms, and also from the breakdown of some [[amino acid]]s. Bacteria of the genus ''[[Propionibacterium]]'' produce propionic acid as the end-product of their [[anaerobic respiration|anaerobic]] metabolism.  This class of bacteria is commonly found in the stomachs of [[ruminant]]s and the [[Cutibacterium acnes|sweat glands of humans]], and their activity is partially responsible for the odor of [[Emmental cheese]], [[Swiss cheese (North America)|American "Swiss cheese"]] and [[sweat]].

The metabolism of propionic acid begins with its conversion to propionyl [[coenzyme A]], the usual first step in the metabolism of [[carboxylic acid]]s.  Since propionic acid has three carbons, propionyl-CoA cannot directly enter either [[beta oxidation]] or the [[citric acid cycle]]s.  In most [[vertebrate]]s, propionyl-CoA is [[carboxylation|carboxylated]] to <small>D</small>-[[methylmalonyl-CoA]], which is [[Isomerisation|isomerised]] to <small>L</small>-methylmalonyl-CoA. A [[vitamin B12|vitamin B<sub>12</sub>]]-dependent enzyme catalyzes rearrangement of <small>L</small>-methylmalonyl-CoA to [[succinyl-CoA]], which is an intermediate of the citric acid cycle and can be readily incorporated there.<ref>{{Cite book|last=Lehninger, Albert L.|url=https://www.worldcat.org/oclc/55476414|title=Lehninger principles of biochemistry|date=2005|publisher=W.H. Freeman|others=Nelson, David L. (David Lee), 1942-, Cox, Michael M.|isbn=0-7167-4339-6|edition=Fourth|location=New York|oclc=55476414}}</ref>

Propionic acid serves as a substrate for [[hepatic]] [[gluconeogenesis]] via conversion to succinyl-CoA.<ref>{{cite journal|last1=Aschenbach|first1=JR|last2=Kristensen|first2=NB|last3=Donkin|first3=SS|last4=Hammon|first4=HM|last5=Penner|first5=GB|date=December 2010|title=Gluconeogenesis in dairy cows: the secret of making sweet milk from sour dough.|journal=IUBMB Life|volume=62|issue=12|pages=869–77|doi=10.1002/iub.400|pmid=21171012|doi-access=free|s2cid=21117076}}</ref><ref>{{Cite journal|last1=Perry|first1=Rachel J.|last2=Borders|first2=Candace B.|last3=Cline|first3=Gary W.|last4=Zhang|first4=Xian-Man|last5=Alves|first5=Tiago C.|last6=Petersen|first6=Kitt Falk|last7=Rothman|first7=Douglas L.|last8=Kibbey|first8=Richard G.|last9=Shulman|first9=Gerald I.|date=21 March 2016|title=Propionate Increases Hepatic Pyruvate Cycling and Anaplerosis and Alters Mitochondrial Metabolism|journal=Journal of Biological Chemistry|volume=291|issue=23|pages=12161–12170|doi=10.1074/jbc.m116.720631|pmid=27002151|pmc=4933266|issn=0021-9258|doi-access=free}}</ref> Additionally, [[Exogeny|exogenous]] propionic acid administration results in more [[Endogeny (biology)|endogenous]] glucose production than can be accounted for by gluconeogenic conversion alone.<ref>{{Cite journal|last=Ringer|first=A. I.|date=2 August 1912|title=The Quantitative Conversion of Propionic Acid into Glucose|url=https://www.jbc.org/content/12/3/511.citation|journal=Journal of Biological Chemistry|volume=12|pages=511–515|doi=10.1016/S0021-9258(18)88686-0|doi-access=free}}</ref> Exogenous propionic acid may [[upregulate]] endogenous glucose production via increases in [[norepinephrine]] and [[glucagon]], suggesting that chronic ingestion of propionic acid may have adverse metabolic consequences.<ref>{{Cite journal|last1=Tirosh|first1=Amir|last2=Calay|first2=Ediz S.|last3=Tuncman|first3=Gurol|last4=Claiborn|first4=Kathryn C.|last5=Inouye|first5=Karen E.|last6=Eguchi|first6=Kosei|last7=Alcala|first7=Michael|last8=Rathaus|first8=Moran|last9=Hollander|first9=Kenneth S.|last10=Ron|first10=Idit|last11=Livne|first11=Rinat|date=24 April 2019|title=The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans|journal=Science Translational Medicine|volume=11|issue=489|pages=eaav0120|doi=10.1126/scitranslmed.aav0120|pmid=31019023|issn=1946-6234|doi-access=free}}</ref>

In [[propionic acidemia]], a rare inherited genetic disorder, propionate acts as a metabolic toxin in liver cells by accumulating in mitochondria as propionyl-CoA and its derivative, methylcitrate, two tricarboxylic acid cycle inhibitors.  Propanoate is metabolized oxidatively by [[glia]], which suggests astrocytic vulnerability in propionic acidemia when intramitochondrial propionyl-CoA may accumulate. Propionic acidemia may alter both neuronal and glial gene expression by affecting histone acetylation.<ref name="macfabe">{{cite journal
|author1=D. F. MacFabe |author2=D. P. Cain |author3=K. Rodriguez-Capote |author4=A. E. Franklin |author5=J. E. Hoffman |author6=F. Boon |author7=A. R. Taylor |author8=M. Kavaliers |author9=K.-P. Ossenkopp | journal = Behavioural Brain Research | title = Neurobiological effects of intraventricular propionic acid in rats: Possible role of short-chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders | year = 2007 | volume = 176 | issue = 1 | pages = 149–169 | doi = 10.1016/j.bbr.2006.07.025 |pmid=16950524 |s2cid=3054752 }}</ref><ref>{{cite journal |author1=N. H. T. Nguyen |author2=C. Morland |author3=S. Villa Gonzalez |author4=F. Rise |author5=J. Storm-Mathisen |author6=V. Gundersen |author7=B. Hassel | journal = Journal of Neurochemistry | title = Propionate increases neuronal histone acetylation, but is metabolized oxidatively by glia. Relevance for propionic acidemia | year = 2007 | volume = 101 | pmid = 17286595 | issue = 3 | pages = 806–814 | doi = 10.1111/j.1471-4159.2006.04397.x |s2cid=514557 |doi-access=free }}</ref>  When propionic acid is infused directly into rodents' brains, it produces reversible behavior (e.g., [[hyperactivity]], [[dystonia]], social impairment, [[perseveration]]) and brain changes (e.g., innate neuroinflammation, glutathione depletion) that may be used as a means to model [[autism]] in rats.<ref name="macfabe" />

===Human occurrence===
The human skin is host of several species of ''Propionibacteria''.  The most notable one is the ''[[Cutibacterium acnes]]'' (formerly known as ''Propionibacterium acnes''), which lives mainly in the [[sebaceous gland]]s of the skin and is one of the principal causes of [[acne]].<ref>{{cite journal |doi=10.1016/j.clindermatol.2004.03.005 |title=Acne and propionibacterium acnes |year=2004 |last1=Bojar |first1=Richard A. |last2=Holland |first2=Keith T. |journal=Clinics in Dermatology |volume=22 |issue=5 |pages=375–379 |pmid=15556721 }}</ref> Propionate is observed to be among the most common [[short-chain fatty acid]]s produced in the [[large intestine]] of humans by [[gut microbiome|gut microbiota]] in response to indigestible carbohydrates ([[dietary fiber]]) in the diet.<ref>{{cite journal |last1=Cani |first1=Patrice D. |last2=Knauf |first2=Claude |title=How gut microbes talk to organs: The role of endocrine and nervous routes |journal=Molecular Metabolism |date=27 May 2016 |volume=5 |issue=9 |pages=743–752 |doi=10.1016/j.molmet.2016.05.011 |pmid=27617197 |pmc=5004142 }}</ref><ref name = metab>{{cite journal|last1=den Besten |first1=G |last2=van Eunen |first2=K |last3=Groen |first3=AK |last4=Venema |first4=K|last5=Reijngoud|first5=DJ|last6=Bakker|first6=BM|title=The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.|journal=Journal of Lipid Research|date=September 2013|volume=54|issue=9|pages=2325–40|doi=10.1194/jlr.R036012 |doi-access=free |pmid=23821742|pmc=3735932}}</ref> The role of the gut microbiota and their metabolites, including propionate, in mediating brain function has been reviewed.<ref>{{cite journal |doi=10.1038/mp.2016.50 |doi-access=free |title=From gut dysbiosis to altered brain function and mental illness: Mechanisms and pathways |year=2016 |last1=Rogers |first1=G. B. |last2=Keating |first2=D. J. |last3=Young |first3=R. L. |last4=Wong |first4=M-L |last5=Licinio |first5=J. |last6=Wesselingh |first6=S. |journal=Molecular Psychiatry |volume=21 |issue=6 |pages=738–748 |pmid=27090305 |pmc=4879184 |s2cid=18589882 }}</ref>

A study in mice suggests that propionate is produced by the bacteria of the genus ''[[Bacteroides]]'' in the gut, and that it offers some protection against ''[[Salmonella]]'' there.<ref>{{cite journal |doi=10.1016/j.chom.2018.07.002   |title=A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection |year=2018 |last1=Jacobson |first1=Amanda |last2=Lam |first2=Lilian |last3=Rajendram |first3=Manohary |last4=Tamburini |first4=Fiona |last5=Honeycutt |first5=Jared |last6=Pham |first6=Trung |last7=Van Treuren |first7=Will |last8=Pruss |first8=Kali |last9=Stabler |first9=Stephen Russell |last10=Lugo |first10=Kyler |last11=Bouley |first11=Donna M. |last12=Vilches-Moure |first12=Jose G. |last13=Smith |first13=Mark |last14=Sonnenburg |first14=Justin L. |last15=Bhatt |first15=Ami S. |last16=Huang |first16=Kerwyn Casey |last17=Monack |first17=Denise |journal=Cell Host & Microbe |volume=24 |issue=2 |pages=296–307.e7 |pmid=30057174 |pmc=6223613 }}</ref> Another study finds that fatty acid propionate can calm the immune cells that drive up blood pressure, thereby protecting the body from damaging effects of high blood pressure.<ref>{{cite journal |doi=10.1161/CIRCULATIONAHA.118.036652 |title=Short-Chain Fatty Acid Propionate Protects from Hypertensive Cardiovascular Damage |year=2019 |last1=Bartolomaeus |first1=Hendrik |last2=Balogh |first2=András |last3=Yakoub |first3=Mina |last4=Homann |first4=Susanne |last5=Markó |first5=Lajos |last6=Höges |first6=Sascha |last7=Tsvetkov |first7=Dmitry |last8=Krannich |first8=Alexander |last9=Wundersitz |first9=Sebastian |last10=Avery |first10=Ellen G. |last11=Haase |first11=Nadine |last12=Kräker |first12=Kristin |last13=Hering |first13=Lydia |last14=Maase |first14=Martina |last15=Kusche-Vihrog |first15=Kristina |last16=Grandoch |first16=Maria |last17=Fielitz |first17=Jens |last18=Kempa |first18=Stefan |last19=Gollasch |first19=Maik |last20=Zhumadilov |first20=Zhaxybay |last21=Kozhakhmetov |first21=Samat |last22=Kushugulova |first22=Almagul |last23=Eckardt |first23=Kai-Uwe |last24=Dechend |first24=Ralf |last25=Rump |first25=Lars Christian |last26=Forslund |first26=Sofia K. |last27=Müller |first27=Dominik N. |last28=Stegbauer |first28=Johannes |last29=Wilck |first29=Nicola |journal=Circulation |volume=139 |issue=11 |pages=1407–1421 |pmid=30586752 |pmc=6416008 }}</ref>

=== Bacteriology ===
The Bacteria species ''[[Coprothermobacter platensis]]'' produces propionate when fermenting gelatin.<ref>{{Cite journal|last1=Etchebehere|first1=C.|last2=Pavan|first2=M. E.|last3=Zorzópulos|first3=J.|last4=Soubes|first4=M.|last5=Muxí|first5=L.|date=October 1998|title=Coprothermobacter platensis sp. nov., a new anaerobic proteolytic thermophilic bacterium isolated from an anaerobic mesophilic sludge|journal=International Journal of Systematic Bacteriology|volume=48 Pt 4|issue=4|pages=1297–1304|doi=10.1099/00207713-48-4-1297|issn=0020-7713|pmid=9828430|doi-access=free}}</ref> ''[[Prevotella brevis]]'' and ''Prevotella ruminicola'' also generate propionate when fermenting glucose.<ref>{{Cite web |last1=Zhang |first1=Bo |last2=Lingga |first2=Christopher |last3=De Groot |first3=Hannah |last4=Hackmann |first4=Timothy J |date=September 30, 2023 |title=The oxidoreductase activity of Rnf balances redox cofactors during fermentation of glucose to propionate in Prevotella |url=https://www.researchgate.net/publication/374334665 |access-date=September 26, 2024 |website=Research Gate}}</ref>