Pyruvic acid

{{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{{cite book | title = Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = The Royal Society of Chemistry | date = 2014 | location = Cambridge | page = 748 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4}}

| SystematicName = 2-Oxopropionic acid

| OtherNames = Pyruvic acid
α-Ketopropionic acid
Acetylformic acid
Pyroracemic acid
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 = C₃H₄O₃

| MolarMass = 88.06{{nbsp}}g/mol

| Density = 1.250{{nbsp}}g/cm³

| MeltingPtC = 11.8

| BoilingPtC = 165

| pKa = 2.50{{cite book|last=Dawson|first=R. M. C.|display-authors=etal|title=Data for Biochemical Research|location= Oxford|publisher= Clarendon Press|date= 1959}}

}}

| Section4 = {{Chembox Related

| OtherAnions = Pyruvate
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100px

| OtherFunction_label = keto-acids, carboxylic acids

| OtherFunction = {{ubl

}}

| OtherCompounds = {{ubl

}}

Pyruvic acid (CH₃COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH₃COCOO⁻, is an intermediate in several metabolic pathways throughout the cell.

Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or converted to fatty acids through a reaction with acetyl-CoA.{{cite book|first=Stuart Ira|last= Fox|title= Human Physiology|edition=12th|publisher=McGraw=Hill|date=2011|page=146}}{{ISBN missing}} 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 cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration), and alternatively ferments to produce lactate when oxygen is lacking.{{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}}

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.{{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 }}{{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 }} The correct molecular structure was deduced by the 1870s.{{cite journal |doi=10.1039/CA8783400019 |title=Pyruvic acid |journal=Journal of the Chemical Society, Abstracts |year=1878 |volume=34 |page=31 }}

Pyruvic acid is a colorless liquid with a smell similar to that of acetic acid and is miscible with water.{{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}} In the laboratory, pyruvic acid may be prepared by heating a mixture of tartaric acid and potassium hydrogen sulfate,{{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}} 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}}

:CH₃COCl + KCN → CH₃COCN + KCl

:CH₃COCN → CH₃COCOOH

Biochemistry

Pyruvate is an important chemical compound in biochemistry. It is the output of the metabolism of glucose known as glycolysis.{{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}} One molecule of glucose breaks down into two molecules of pyruvate, which are then used to provide further energy, in one of two ways. Pyruvate is converted into acetyl-coenzyme A, which is the main input for a series of reactions known as the Krebs cycle (also known as the citric acid cycle or tricarboxylic acid cycle). Pyruvate is also converted to oxaloacetate by an 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 anaerobically, creating lactate in animals and ethanol in plants and microorganisms (and in carp{{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}}). Pyruvate from glycolysis is converted by fermentation to lactate using the enzyme lactate dehydrogenase and the coenzyme NADH in lactate fermentation, or to acetaldehyde (with the enzyme pyruvate decarboxylase) and then to ethanol in alcoholic fermentation.{{Citation needed|date=December 2023}}

Pyruvate is a key intersection in the network of metabolic pathways. Pyruvate can be converted into carbohydrates via gluconeogenesis, to fatty acids 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, comparing blood content of pyruvate (shown in violet near middle) with other constituents.]]

=Pyruvic acid production by glycolysis=

In the last step of glycolysis, 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)=ADP

| minor_forward_product(s)=ATP

| minor_reverse_substrate(s)=ATP

| minor_reverse_product(s)=ADP

| substrate_image=phosphoenolpyruvate_wpmp.svg

| product_image=Pyruvic-acid-2D-skeletal.svg

| product_image_size=90px

}}

=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)= CoA + NAD⁺

| minor_forward_product(s)= CO₂ + NADH + H⁺

| 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 oxaloacetate.

{{Enzymatic Reaction

| forward_enzyme=pyruvate carboxylase

| reverse_enzyme=

| substrate=pyruvate

| product=oxaloacetate

| reaction_direction_(forward/reversible/reverse)=forward

| minor_forward_substrate(s)= ATP + CO₂

| minor_forward_product(s)= ADP + P_i

| 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 lactate.

{{Enzymatic Reaction

| forward_enzyme=lactate dehydrogenase

| reverse_enzyme=

| substrate=pyruvate

| product=lactate

| reaction_direction_(forward/reversible/reverse)=reversible

| minor_forward_substrate(s)= NADH

| minor_forward_product(s)= NAD⁺

| minor_reverse_substrate(s)= NAD⁺

| 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 aerosols.{{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}}

Uses

Pyruvate is sold as a weight-loss supplement, though credible science has yet to back this claim. A systematic review of six 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 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.{{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}}

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.{{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}}{{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}}

Notes

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 }}