View source for Pyruvic acid

{{short description|Simplest of the alpha-keto acids}}
{{chembox
| Verifiedfields = changed
| Watchedfields  = changed
| verifiedrevid  = 464364811
| Name           = Pyruvic acid
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageFileL1    = Brenztraubensäure.svg
| ImageClassL1   = skin-invert-image
| ImageFileR1    = Pyruvic-acid-3D-balls.png
| PIN            = 2-Oxopropanoic acid<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 748 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4}}</ref>
| SystematicName = 2-Oxopropionic acid
| OtherNames     = Pyruvic acid<ref name=iupac2013 /><br />α-Ketopropionic acid<br />Acetylformic acid<br />Pyroracemic acid<br/>Acetylcarboxylic acid
| Section1       = {{Chembox Identifiers
| IUPHAR_ligand = 4809
| PubChem = 1060
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8558G7RUTR
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1162144
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C3H4O3/c1-2(4)3(5)6/h1H3,(H,5,6)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LCTONWCANYUPML-UHFFFAOYSA-N
| Abbreviations = Pyr
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 127-17-3
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1031
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00119
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 32816
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C00022
| SMILES = O=C(C(=O)O)C
}}
| Section2       = {{Chembox Properties
| Formula = C<sub>3</sub>H<sub>4</sub>O<sub>3</sub>
| MolarMass = 88.06{{nbsp}}g/mol
| Density = 1.250{{nbsp}}g/cm<sup>3</sup>
| MeltingPtC = 11.8
| BoilingPtC = 165
| pKa = 2.50<ref>{{cite book|last=Dawson|first=R. M. C.|display-authors=etal|title=Data for Biochemical Research|location= Oxford|publisher= Clarendon Press|date= 1959}}</ref>
}}
| Section4       = {{Chembox Related
| OtherAnions = [[Pyruvate]]<br /> [[File:Pyruvate_skeletal.svg|99px]]<br />[[File:Pyruvate-3D-balls.png|100px]]
| OtherFunction_label = [[keto-acid]]s, [[carboxylic acid]]s
| OtherFunction = {{ubl
 | [[Acetic acid]]
 | [[Glyoxylic acid]]
 | [[Oxalic acid]]
 | [[Propionic acid]]
 | [[Acetoacetic acid]]
}}
| OtherCompounds = {{ubl
 | [[Propionaldehyde]]
 | [[Glyceraldehyde]]
 | [[Methylglyoxal]]
 | [[Sodium pyruvate]]
}}
}}
}}

'''Pyruvic acid''' (CH<sub>3</sub>COCOOH) is the simplest of the [[keto acids|alpha-keto acids]], with a [[carboxylic acid]] and a [[ketone]] functional group. '''Pyruvate''', the [[conjugate acid|conjugate base]], CH<sub>3</sub>COCOO<sup>−</sup>, is an [[metabolic intermediate|intermediate]] in several [[metabolic pathway]]s throughout the cell.

Pyruvic acid can be made from [[glucose]] through [[glycolysis]], converted back to [[carbohydrate]]s (such as glucose) via [[gluconeogenesis]], or converted to [[fatty acid]]s through a reaction with [[acetyl-CoA]].<ref>{{cite book|first=Stuart Ira|last= Fox|title= Human Physiology|edition=12th|publisher=McGraw=Hill|date=2011|page=146}}{{ISBN missing}}</ref> It can also be used to construct the amino acid [[alanine]] and can be converted into [[ethanol]] or [[lactic acid]] via [[fermentation]].

Pyruvic acid supplies energy to [[cell (biology)|cells]] through the [[citric acid cycle]] (also known as the Krebs cycle) when oxygen is present ([[aerobic respiration]]), and alternatively [[lactic acid fermentation|ferments]] to produce [[lactic acid|lactate]] when oxygen is lacking.<ref>{{cite web|last1=Ophardt|first1=Charles E.|title=Pyruvic Acid - Cross Roads Compound|url=http://chemistry.elmhurst.edu/vchembook/603pyruvic.html|website=Virtual Chembook|publisher=Elmhurst College|access-date=April 7, 2017|archive-date=July 31, 2018|archive-url=https://web.archive.org/web/20180731021548/http://chemistry.elmhurst.edu/vchembook/603pyruvic.html}}</ref>

==Chemistry==
In 1834, [[Théophile-Jules Pelouze]] distilled [[tartaric acid]] and isolated [[glutaric acid]] and another unknown organic acid. [[Jöns Jacob Berzelius]] characterized this other acid the following year and named pyruvic acid because it was distilled using heat.<ref>{{cite book|last=Thomson|first= Thomas |author-link=Thomas Thomson (chemist)|title=Chemistry of organic bodies, vegetables|url=https://books.google.com/books?id=Wq45AAAAcAAJ |access-date=December 1, 2010|year= 1838|publisher=J. B. Baillière|location=London|page=65|chapter=Chapter II. Of fixed acids Section|chapter-url=https://books.google.com/books?id=Wq45AAAAcAAJ&pg=PA65 }}</ref><ref>{{cite journal |last1=Berzelius |first1=J. |title=Ueber eine neue, durch Destillation von Wein-und Traubensäure erhaltene Säure |journal=Annalen der Pharmacie |date=1835 |volume=13 |issue=1 |pages=61–63 |doi=10.1002/jlac.18350130109|url=https://zenodo.org/record/1951856 }}</ref> The correct molecular structure was deduced by the 1870s.<ref>{{cite journal |doi=10.1039/CA8783400019 |title=Pyruvic acid |journal=Journal of the Chemical Society, Abstracts |year=1878 |volume=34 |page=31 }}</ref> 

Pyruvic acid is a colorless liquid with a smell similar to that of [[acetic acid]] and is [[miscible]] with water.<ref>{{cite web|title=Pyruvic Acid|url=http://www.chemspider.com/Chemical-Structure.1031.html |website=ChemSpider|publisher=Royal Society of Chemistry|access-date=21 April 2017}}</ref> In the laboratory, pyruvic acid may be prepared by heating a mixture of [[tartaric acid]] and [[potassium hydrogen sulfate]],<ref>{{OrgSynth|title=Pyruvic Acid|last1=Howard|first1=J. W.|last2=Fraser|first2=W. A.|prep=cv1p0475 |collvol=1| collvolpages=475 |volume=4|page=63|date=1925}}</ref> by the [[oxidation]] of [[propylene glycol]] by a strong oxidizer (e.g., [[potassium permanganate]] or [[bleach]]), or by the hydrolysis of [[acetyl cyanide]], formed by reaction of [[acetyl chloride]] with [[potassium cyanide]]:{{Citation needed|date=December 2023}}
:CH<sub>3</sub>COCl + KCN → CH<sub>3</sub>COCN + KCl
:CH<sub>3</sub>COCN → CH<sub>3</sub>COCOOH

==Biochemistry==
{{Citations needed|date=December 2023}}
Pyruvate is an important [[chemical compound]] in [[biochemistry]]. It is the output of the metabolism of [[glucose]] known as [[glycolysis]].<ref name="lehninger528">{{Cite book|title=Principles of Biochemistry|edition=5th|first1=Albert L.|first2=David L.|first3=Michael M.|last1=Lehninger|last2=Nelson|last3=Cox|publisher=W. H. Freeman and Company|location=New York, NY|year=2008|isbn=978-0-7167-7108-1|page=[https://archive.org/details/lehningerprincip00lehn_1/page/528 528]|url-access=registration|url=https://archive.org/details/lehningerprincip00lehn_1/page/528}}</ref> One molecule of [[glucose]] breaks down into two molecules of pyruvate,<ref name="lehninger528" /> which are then used to provide further energy, in one of two ways. Pyruvate is converted into [[Acetyl-CoA|acetyl-coenzyme A]], which is the main input for a series of reactions known as the [[citric acid cycle|Krebs cycle]] (also known as the citric acid cycle or tricarboxylic acid cycle). Pyruvate is also  converted to [[oxaloacetate]] by an [[anaplerotic reactions|anaplerotic reaction]], which replenishes Krebs cycle intermediates; also, the oxaloacetate is used for [[gluconeogenesis]].{{Citation needed|date=December 2023}}

These reactions are named after [[Hans Adolf Krebs]], the biochemist awarded the 1953 [[Nobel Prize]] for physiology, jointly with [[Fritz Lipmann]], for research into metabolic processes. The cycle is also known as the [[citric acid cycle]] or tricarboxylic acid cycle, because citric acid is one of the intermediate compounds formed during the reactions.{{Citation needed|date=December 2023}}

If insufficient oxygen is available, the acid is broken down [[anaerobe|anaerobically]], creating [[lactic acid|lactate]] in animals and [[ethanol]] in plants and microorganisms (and in [[carp]]<ref>{{cite book|author1=Aren van Waarde|author2=G. Van den Thillart|author3-link=Maria Verhagen|author3=Maria Verhagen|title=Surviving Hypoxia|date=1993|isbn=0-8493-4226-0|pages=157–170|chapter=Ethanol Formation and pH-Regulation in Fish|publisher=CRC Press |author1-link=Aren van Waarde|hdl=11370/3196a88e-a978-4293-8f6f-cd6876d8c428}}</ref>). Pyruvate from glycolysis is converted by [[fermentation (biochemistry)|fermentation]] to [[lactic acid|lactate]] using the [[enzyme]] [[lactate dehydrogenase]] and the [[coenzyme]] [[NADH]] in lactate [[fermentation (biochemistry)|fermentation]], or to [[acetaldehyde]] (with the enzyme [[pyruvate decarboxylase]]) and then to [[ethanol]] in [[Ethanol fermentation|alcoholic fermentation]].{{Citation needed|date=December 2023}}

Pyruvate is a key intersection in the network of [[metabolic pathway]]s. Pyruvate can be converted into [[carbohydrate]]s via [[gluconeogenesis]], to [[fatty acid]]s or energy through [[acetyl-CoA]], to the [[amino acid]] [[alanine]], and to [[ethanol]]. Therefore, it unites several key metabolic processes.{{Citation needed|date=December 2023}}

[[File:Blood values sorted by mass and molar concentration.png|thumb|450px|[[Reference ranges for blood tests]], comparing blood content of pyruvate (shown in violet near middle) with other constituents.]]

===Pyruvic acid production by glycolysis===
In the last step of [[glycolysis]], [[phosphoenolpyruvic acid|phosphoenolpyruvate]] (PEP) is converted to pyruvate by [[pyruvate kinase]].  This reaction is strongly exergonic and irreversible; in [[gluconeogenesis]], it takes two enzymes, [[pyruvate carboxylase]] and [[PEP carboxykinase]], to catalyze the reverse transformation of pyruvate to PEP.{{Citation needed|date=December 2023}}
{{Enzymatic reaction
| forward_enzyme=[[pyruvate kinase]]
| reverse_enzyme=[[pyruvate carboxylase]] and [[PEP carboxykinase]]
| substrate=[[phosphoenolpyruvate]]
| product=pyruvic acid
| reaction_direction_(forward/reversible/reverse)=reversible
| minor_forward_substrate(s)=[[Adenosine diphosphate|ADP]]
| minor_forward_product(s)=[[adenosine triphosphate|ATP]]
| minor_reverse_substrate(s)=[[adenosine triphosphate|ATP]]
| minor_reverse_product(s)=[[Adenosine diphosphate|ADP]]
| substrate_image=phosphoenolpyruvate_wpmp.svg
| product_image=Pyruvic-acid-2D-skeletal.svg
| product_image_size=90px
}}
{{KEGG compound|C00074}} {{KEGG enzyme|2.7.1.40}} {{KEGG compound|C00022}}

{{GlycolysisGluconeogenesis_WP534|highlight=Pyruvic_acid__alt1}}

===Decarboxylation to acetyl CoA===
[[Pyruvate decarboxylation]] by the [[pyruvate dehydrogenase complex]] produces [[acetyl-CoA]].
{{Enzymatic Reaction
| forward_enzyme=[[pyruvate dehydrogenase complex]]
| reverse_enzyme=
| substrate=pyruvate
| product=[[acetyl-CoA]]
| reaction_direction_(forward/reversible/reverse)=forward
| minor_forward_substrate(s)= [[Coenzyme A|CoA]] '''+''' NAD<sup>+</sup>
| minor_forward_product(s)= CO<sub>2</sub> '''+''' NADH '''+''' H<sup>+</sup>
| minor_reverse_substrate(s)=
| minor_reverse_product(s)=
| substrate_image=pyruvate_wpmp.png
| product_image=Acetyl-CoA.svg
}}

===Carboxylation to oxaloacetate===
Carboxylation by [[pyruvate carboxylase]] produces [[oxaloacetic acid|oxaloacetate]].
{{Enzymatic Reaction
| forward_enzyme=[[pyruvate carboxylase]]
| reverse_enzyme=
| substrate=pyruvate
| product=[[oxaloacetate]]
| reaction_direction_(forward/reversible/reverse)=forward
| minor_forward_substrate(s)= ATP '''+''' CO<sub>2</sub>
| minor_forward_product(s)= ADP '''+''' P<sub>i</sub>
| minor_reverse_substrate(s)=
| minor_reverse_product(s)=
| substrate_image=pyruvate_wpmp.png
| product_image=Oxaloacetate_wpmp.png
}}

===Transamination to alanine===
Transamination by [[alanine transaminase]] produces [[alanine]].
{{Enzymatic Reaction
| forward_enzyme=[[alanine transaminase]]
| reverse_enzyme=
| substrate=pyruvate
| product=[[alanine]]
| reaction_direction_(forward/reversible/reverse)=reversible
| minor_forward_substrate(s)= [[glutamate]]
| minor_forward_product(s)= [[α-ketoglutarate]]
| minor_reverse_substrate(s)= [[α-ketoglutarate]]
| minor_reverse_product(s)= [[glutamate]]
| substrate_image=pyruvate_wpmp.png
| product_image=L-alanine-skeletal.svg
| product_image_size=100px
}}

===Reduction to lactate===
Reduction by [[lactate dehydrogenase]] produces [[lactic acid|lactate]].
{{Enzymatic Reaction
| forward_enzyme=[[lactate dehydrogenase]]
| reverse_enzyme=
| substrate=pyruvate
| product=[[lactic acid|lactate]]
| reaction_direction_(forward/reversible/reverse)=reversible
| minor_forward_substrate(s)= NADH
| minor_forward_product(s)= NAD<sup>+</sup>
| minor_reverse_substrate(s)= NAD<sup>+</sup>
| minor_reverse_product(s)= NADH
| substrate_image=pyruvate_wpmp.png
| product_image=Lactic-acid-skeletal.svg
}}

=== Environmental chemistry ===
Pyruvic acid is an abundant carboxylic acid in [[secondary organic aerosol]]s.<ref>{{Cite journal|last1=Guzman|first1=Marcelo I.|last2=Eugene|first2=Alexis J.|date=2021-09-01|title=Aqueous Photochemistry of 2-Oxocarboxylic Acids: Evidence, Mechanisms, and Atmospheric Impact|journal=Molecules|language=en|volume=26|issue=17|page=5278|doi=10.3390/molecules26175278|pmid=34500711|pmc=8433822|doi-access=free}}</ref>

==Uses==
Pyruvate is sold as a [[Anti-obesity medication|weight-loss supplement]], though credible science has yet to back this claim. A [[Clinical research|systematic review]] of six [[Clinical trial|trials]] found a statistically significant difference in body weight with pyruvate compared to [[placebo]]. However, all of the trials had methodological weaknesses and the magnitude of the effect was small. The review also identified [[Adverse effect|adverse events]] associated with pyruvate such as diarrhea, bloating, gas, and increase in [[low-density lipoprotein]] (LDL) cholesterol. The authors concluded that there was insufficient evidence to support the use of pyruvate for weight loss.<ref>{{cite journal|last1=Onakpoya|first1= I.|last2= Hunt|first2= K.|last3=Wider|first3= B.|last4= Ernst |first4=E.|title=Pyruvate supplementation for weight loss: a systematic review and meta-analysis of randomized clinical trials|doi=10.1080/10408398.2011.565890|journal=Crit. Rev. Food Sci. Nutr.|date=2014|volume=54|issue=1|pages=17–23|pmid=24188231|s2cid= 20241217}}</ref>

There is also ''[[in vitro]]'' as well as ''[[in vivo]]'' evidence in hearts that pyruvate improves metabolism by [[NADH]] production stimulation and increases cardiac function.<ref name="Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate.">{{cite journal |pmid=26142699 |title=Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate. |last1=Jaimes |first1=R. III |doi=10.1007/s00424-015-1717-1 |date=Jul 2015 |journal=Pflügers Arch. |volume=468 |issue=1 |pmc=4701640 |pages=131–42}}</ref><ref>{{Cite journal|last1=Hermann|first1=H. P.|last2=Pieske|first2=B.|last3=Schwarzmüller|first3=E.|last4=Keul|first4=J.|last5=Just|first5=H.|last6=Hasenfuss|first6=G.|date=1999-04-17|title=Haemodynamic effects of intracoronary pyruvate in patients with congestive heart failure: an open study|journal=Lancet |volume=353|issue=9161|pages=1321–1323|issn=0140-6736|pmid=10218531|doi=10.1016/s0140-6736(98)06423-x|s2cid=25126646}}</ref>

== See also ==
* [[Pyruvate scale]]
* [[Uvitonic acid]]

== Notes ==
{{reflist}}

== References ==
* {{Cite journal| last3 = Filley | first1 = G. D. | first2 = N. Z.| last2 = Boctor | first3 = T. R. | first4 = R. M.| last5 = Scott| last4 = Hazen| last7 = Yoder | first5 = J. H. | first6 = A.| last1 = Cody | first7 = H. S. Jr| last6 = Sharma| title = Primordial Carbonylated Iron-Sulfur Compounds and the Synthesis of Pyruvate | journal = Science | volume = 289| issue = 5483 | pages = 1337–1340 | year = 2000| pmid = 10958777 | doi = 10.1126/science.289.5483.1337|bibcode = 2000Sci...289.1337C | s2cid = 14911449 }}

==External links==
* [http://gmd.mpimp-golm.mpg.de/Spectrums/24255dbc-f607-4bd7-aac1-fc17b3663b9e.aspx Pyruvic acid mass spectrum]
{{commons}}

{{Glycolysis}}
{{Amino acid metabolism intermediates}}

{{Authority control}}

{{DEFAULTSORT:Pyruvic Acid}}
[[Category:Alpha-keto acids]]
[[Category:Cellular respiration]]
[[Category:Exercise physiology]]
[[Category:Metabolism]]
[[Category:Glycolysis]]