| Revision as of 16:11, 18 January 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL KEGG.← Previous edit |
Latest revision as of 22:06, 7 August 2024 edit undo2601:580:8080:2e50:2d6f:6468:2ddd:f1ae (talk) →Chemical structure |
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{{chembox |
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{{chembox |
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| verifiedrevid = 401608896 |
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| ImageFileL1 = Pyruvaldehyde.svg |
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| verifiedrevid = 408606247 |
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| ImageSizeL1 = 120px |
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| ImageFileL1_Ref = {{chemboximage|correct|??}} |
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| ImageNameL1 = Skeletal formula |
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| ImageFileL1 = Pyruvaldehyde.svg |
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| ImageFileR1 = Methylglyoxal-3D-balls.png |
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| ImageSizeR1 = 125px |
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| ImageSizeL1 = 120 |
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| ImageNameL1 = Skeletal formula |
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| ImageNameR1 = Ball-and-stick model |
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| ImageFileR1 = Methylglyoxal molecule ball.png |
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| IUPACName = 2-oxopropanal |
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| OtherNames = |
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| ImageSizeR1 = 120 |
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| ImageAltR1 = Ball-and-stick model of methylglyoxal |
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|Section1= {{Chembox Identifiers |
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| PIN = 2-Oxopropanal |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| OtherNames = Pyruvaldehyde |
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|Section1={{Chembox Identifiers |
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| IUPHAR_ligand = 6303 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 722KLD7415 |
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| UNII = 722KLD7415 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = C00546 |
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| KEGG = C00546 |
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| InChI = 1/C3H4O2/c1-3(5)2-4/h2H,1H3 |
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| InChI = 1/C3H4O2/c1-3(5)2-4/h2H,1H3 |
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| InChIKey = AIJULSRZWUXGPQ-UHFFFAOYAZ |
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| InChIKey = AIJULSRZWUXGPQ-UHFFFAOYAZ |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 170721 |
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| ChEMBL = 170721 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = AIJULSRZWUXGPQ-UHFFFAOYSA-N |
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| StdInChIKey = AIJULSRZWUXGPQ-UHFFFAOYSA-N |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo=78-98-8 |
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| CASNo = 78-98-8 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo1_Ref = {{cascite|changed|??}} |
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| PubChem=880 |
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| CASNo1 = 1186-47-6 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| CASNo1_Comment = (hydrate) |
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| PubChem = 880 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 857 |
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| ChemSpiderID = 857 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| SMILES=CC(=O)C=O |
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| DrugBank = DB03587 |
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| MeSHName=Methylglyoxal |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 17158 |
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| 3DMet = B00127 |
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| Beilstein = 906750 |
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| SMILES = CC(=O)C=O |
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| MeSHName = Methylglyoxal |
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|Section2= {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=3 | H=4 | O=2 |
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| Formula=C<sub>3</sub>H<sub>4</sub>O<sub>2</sub> |
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| Appearance= Yellow liquid |
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| MolarMass=72.0627 |
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| Density= 1.046{{nbsp}}g/cm<sup>3</sup> |
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| Appearance= |
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| Density= |
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| MeltingPt= |
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| BoilingPtC= 72 |
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| MeltingPt= |
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| MeltingPtC= 25 |
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| BoilingPt= |
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| Solubility= |
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|Section3= {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards= |
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| FlashPt= |
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| AutoignitionPt = |
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| Autoignition= |
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| GHSPictograms = {{GHS05}}{{GHS06}}{{GHS08}} |
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| GHSSignalWord = Danger |
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| HPhrases = {{H-phrases|290|302|315|317|318|319|335|341}} |
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| PPhrases = {{P-phrases|201|202|234|261|264|270|271|272|280|281|301+312|302+352|304+340|305+351+338|308+313|310|312|321|330|332+313|333+313|337+313|362|363|390|403+233|404|405|501}} |
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| Section4 = {{Chembox Related |
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|Section4={{Chembox Related |
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| OtherAnions = |
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| OtherAnions = |
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| Function = ]s, ]s |
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| OtherFunction_label = ]s, ]s |
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| OtherFunction = {{ubl |
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| OtherFunctn = ]<br />]<br />]<br />]<br />]<br />] |
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| ] |
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| OtherCpds = ]<br />]<br />] |
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| OtherCompounds = {{ubl |
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'''Methylglyoxal''' ('''MGO''') is the ] with the formula CH<sub>3</sub>C(O)CHO. It is a reduced derivative of ]. It is a reactive compound that is implicated in the biology of ]. Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressed ].<ref>{{Ullmann|first1=Frieder W.|last1= Lichtenthaler|title=Carbohydrates as Organic Raw Materials|year=2010|doi= 10.1002/14356007.n05_n07}}</ref> |
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'''Methylglyoxal''', also called '''pyruvaldehyde''' or '''2-oxopropanal''' (CH<sub>3</sub>-CO-CH=O or C<sub>3</sub>H<sub>4</sub>O<sub>2</sub>) is the ] form of ]. It has two carbonyl groups, so it is a di] compound. Methylglyoxal is both an aldehyde and a ]. |
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==Chemical structure== |
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In organisms, methylglyoxal is formed as a side-product of several ]s.<ref>{{cite journal|author=Inoue Y, Kimura A |title=Methylglyoxal and regulation of its metabolism in microorganisms|journal=Adv. Microb. Physiol.|volume=37|issue=|pages=177–227 year=1995 |pmid=8540421|doi=10.1016/S0065-2911(08)60146-0|year=1995}}</ref> It may form from 3-amino ], which is an intermediate of ] catabolism, as well as through ]. However, the most important source is ]. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate and dihydroxyacetone phosphate, two intermediates of glycolysis. Since methylglyoxal is highly ] the body developed several detoxification mechanisms. One of these is the ]. Methylglyoxal reacts with ] to form a hemithioacetal. This is converted into ''S''-<small>D</small>-lactoyl-glutathione by ],<ref>{{cite journal|author=Thornalley PJ|title=Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation |journal=Biochem. Soc. Trans.|volume=31|issue=Pt 6|pages=1343–8|year=2003|pmid=14641060|url=http://www.biochemsoctrans.org/bst/031/1343/bst0311343.htm|doi=10.1042/BST0311343 |
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Gaseous methylglyoxal has two ] groups: an ] and a ]. In the presence of water, it exists as hydrates and ]s. The formation of these hydrates is indicative of the high reactivity of MGO, which is relevant to its biological behavior.<ref>{{cite journal |last1=Loeffler|first1=Kirsten W. |last2=Koehler|first2=Charles A. |last3=Paul|first3=Nichole M. |last4=De Haan |first4=David O. | year = 2006 | title = Oligomer Formation in Evaporating Aqueous Glyoxal and Methyl Glyoxal Solutions | journal = Environmental Science & Technology | volume = 40 | issue = 20| pages = 6318–23 | doi = 10.1021/es060810w |pmid=17120559 |bibcode=2006EnST...40.6318L }}</ref> |
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}}</ref> and then further metabolised into <small>D</small>-lactate by ].<ref>{{cite journal|author=Vander Jagt DL|title=Glyoxalase II: molecular characteristics, kinetics and mechanism|journal=Biochem. Soc. Trans.|volume=21|issue=2|pages=522–7|year=1993|pmid=8359524}}</ref> |
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==Biochemistry== |
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Why methylglyoxal is produced remains unknown, but several articles indicate it is involved in the formation of ]s (AGEs). In fact, methylglyoxal is proven to be the most important glycation agent (forming AGEs) <ref>{{cite journal|author=Shinohara M|title=Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis.|journal=J Clin Invest.|volume=101|issue=5|pages=1142–7|year=1998|pmid=9486985|doi=10.1172/JCI119885|last2=Thornalley|first2=PJ|last3=Giardino|first3=I|last4=Beisswenger|first4=P|last5=Thorpe|first5=SR|last6=Onorato|first6=J|last7=Brownlee|first7=M|pmc=508666}}</ref>. In this process, methylglyoxal reacts with free amino groups of ] and ] and with thiol groups of ], forming AGEs. Recent research has identified heat shock protein 27 (]) as a specific target of posttranslational modification by methylglyoxal in human metastatic ] cells.<ref>{{cite journal |author=Bair WB 3rd, Cabello CM, Uchida K, Bause AS, Wondrak GT |title=GLO1 overexpression in human malignant melanoma |journal=Melanoma Res |volume=20 |issue=2 |pages=85–96 |year=2010 |month=April |pmid=20093988 |pmc=2891514 |doi=10.1097/CMR.0b013e3283364903 }}</ref> |
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===Biosynthesis and biodegradation=== |
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Other ] agents include the reducing sugars: |
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In organisms, methylglyoxal is formed as a side-product of several ]s.<ref>{{cite journal|vauthors=Inoue Y, Kimura A |title=Methylglyoxal and regulation of its metabolism in microorganisms|journal=Adv. Microb. Physiol.|volume=37|pages=177–227 |pmid=8540421|doi=10.1016/S0065-2911(08)60146-0|year=1995|series=Advances in Microbial Physiology|isbn=978-0-12-027737-7}}</ref> Methylglyoxal mainly arises as side products of ] involving ] and ]. It is also thought to arise via the degradation of ] and ].<ref name=DRCP/> Illustrative of the myriad pathways to MGO, ] caused 12-fold increase of methylglyoxal from 18 to 231 μg/mg of kidney protein in poisoned mice.<ref>{{cite journal | pmid = 22713464 | doi=10.1016/j.bbrc.2012.06.049 | volume=423 | title=Aristolochic acid-induced accumulation of methylglyoxal and Nε-(carboxymethyl)lysine: an important and novel pathway in the pathogenic mechanism for aristolochic acid nephropathy | year=2012 | journal=Biochem Biophys Res Commun | pages=832–7 | last1 = Li | first1 = YC | last2 = Tsai | first2 = SH | last3 = Chen | first3 = SM | last4 = Chang | first4 = YM | last5 = Huang | first5 = TC | last6 = Huang | first6 = YP | last7 = Chang | first7 = CT | last8 = Lee | first8 = JA| issue=4 }}</ref> It may form from ], which is an intermediate of threonine ], as well as through ]. However, the most important source is ]. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate and ] (DHAP), two intermediates of glycolysis. This conversion is the basis of a potential biotechnological route to the commodity chemical ].<ref name=Ullmann>{{Ullmann|title=Propanediols|first=Carl J. |last=Sullivan |first2=Anja |last2=Kuenz |first3=Klaus‐Dieter |last3=Vorlop|year=2018|doi=10.1002/14356007.a22_163.pub2}}</ref> |
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*], the sugar that stores ], |
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*], a part of milk sugar (]), |
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Since methylglyoxal is highly ], several detoxification mechanisms have evolved. One of these is the ]. Methylglyoxal is detoxified by ]. Glutathione reacts with methylglyoxal to give a ], which converted into ''S''-{{small|D}}-lactoyl-glutathione by ].<ref>{{cite journal|author=Thornalley PJ|title=Glyoxalase I—structure, function and a critical role in the enzymatic defence against glycation |journal=Biochem. Soc. Trans.|volume=31|issue=Pt 6|pages=1343–8|year=2003|pmid=14641060|doi=10.1042/BST0311343 }}</ref> This ] is hydrolyzed to ] by ].<ref>{{cite journal|author=Vander Jagt DL|title=Glyoxalase II: molecular characteristics, kinetics and mechanism|journal=Biochem. Soc. Trans.|volume=21|issue=2|pages=522–7|year=1993|pmid=8359524|doi=10.1042/bst0210522}}</ref> |
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*], an all-cis ] carried into the ] by special ], and |
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*], a component of ]. |
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===Biochemical function=== |
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Methylglyoxal is involved in the formation of ]s (AGEs).<ref name=DRCP>{{cite journal|journal=Diabetes Research and Clinical Practice|volume=148|pages=200–211|year=2019|title=Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer|first1=Justine|last1=Bellier|first2=Marie-Julie|last2=Nokin|first3=Eva|last3= Lardé|first4=Philippe|last4=Karoyan|first5=Olivier|last5=Peulen|first6=Vincent|last6=Castronovo|first7=Akeila|last7=Bellahcène|doi=10.1016/j.diabres.2019.01.002|pmid=30664892|s2cid=58631777}}</ref> In this process, methylglyoxal reacts with free amino groups of ] and ] and with thiol groups of ] forming AGEs. ]s are also heavily susceptible to modification by methylglyoxal and these modifications are elevated in breast cancer.<ref>{{cite journal |vauthors=Galligan JJ, Wepy JA, Streeter MD, Kingsley PJ, Mitchener MM, Wauchope OR, Beavers WN, Rose KL, Wang T, Spiegel DA, Marnett LJ |title=Methylglyoxal-derived posttranslational arginine modifications are abundant histone marks |journal=Proc Natl Acad Sci USA|volume=115 |issue=37 |pages=9228–33 |date=September 2018 |pmid= 30150385|pmc=6140490 |doi=10.1073/pnas.1802901115 |bibcode=2018PNAS..115.9228G |doi-access=free }}</ref><ref>{{cite journal |vauthors=Zheng Q, Omans ND, Leicher R, Osunsade A, Agustinus AS, Finkin-Groner E, D'Ambrosio H, Liu B, Chandarlapaty S, Liu S, David Y |title=Reversible histone glycation is associated with disease-related changes in chromatin architecture |journal=Nat Commun|volume=10 |issue=1 |pages=1289 |date=March 2019 |pmid= 30894531|pmc=6426841 |doi= 10.1038/s41467-019-09192-z |bibcode=2019NatCo..10.1289Z }}</ref> |
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] are induced by reactive ], principally methylglyoxal and ], at a frequency similar to that of ].<ref name = Richarme2017>Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science. 2017 Jul 14;357(6347):208-211. doi: 10.1126/science.aag1095. Epub 2017 Jun 8. PMID 28596309</ref> Such damage, referred to as DNA ], can cause ], breaks in DNA and ].<ref name = Richarme2017/> In humans, a protein DJ-1 (also named ]), has a key role in the repair of glycated DNA bases. |
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===Biomedical aspects=== |
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Due to increased blood glucose levels, methylglyoxal has higher concentrations in ] and has been linked to ] ]. Damage by methylglyoxal to ] through glycation causes a fourfold increase of atherogenesis in diabetics.<ref>{{cite journal|author=Rabbani N|title=Glycation of LDL by methylglyoxal increases arterial atherogenicity. A possible contributor to increased risk of cardiovascular disease in diabetes|journal=Diabetes|date=May 26, 2011|pmid=21617182|doi=10.2337/db11-0085|last2=Godfrey|first2=L|last3=Xue|first3=M|last4=Shaheen|first4=F|last5=Geoffrion|first5=M|last6=Milne|first6=R|last7=Thornalley|first7=PJ|volume=60|issue=7|pages=1973–80|pmc=3121424}}</ref> Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness in ].<ref>. Deutsche-apotheker-zeitung.de (2012-05-21). Retrieved on 2012-06-11.</ref><ref>{{cite journal|doi=10.1038/nm.2750|pmid=22581285|title=Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy|year=2012|last1=Bierhaus|first1=Angelika|last2=Fleming|first2=Thomas|last3=Stoyanov|first3=Stoyan|last4=Leffler|first4=Andreas|last5=Babes|first5=Alexandru|last6=Neacsu|first6=Cristian|last7=Sauer|first7=Susanne K|last8=Eberhardt|first8=Mirjam|last9=Schnölzer|first9=Martina|last10=Lasischka|first10=Felix|last11=Neuhuber|first11=Winfried L|last12=Kichko|first12=Tatjana I|last13=Konrade|first13=Ilze|last14=Elvert|first14=Ralf|last15=Mier|first15=Walter|last16=Pirags|first16=Valdis|last17=Lukic|first17=Ivan K|last18=Morcos|first18=Michael|last19=Dehmer|first19=Thomas|last20=Rabbani|first20=Naila|last21=Thornalley|first21=Paul J|last22=Edelstein|first22=Diane|last23=Nau|first23=Carla|last24=Forbes|first24=Josephine|last25=Humpert|first25=Per M|last26=Schwaninger|first26=Markus|last27=Ziegler|first27=Dan|last28=Stern|first28=David M|last29=Cooper|first29=Mark E|last30=Haberkorn|first30=Uwe|journal=Nature Medicine|volume=18|issue=6|pages=926–33|s2cid=205389296|display-authors=8}}</ref> |
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==Occurrence, other== |
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Methylglyoxal is a component of some kinds of honey, including ]; it appears to have activity against '']'' and '']'' and may help prevent formation of ]s formed by '']''.<ref>{{cite journal|last1=Israili|first1=ZH|title=Antimicrobial properties of honey.|journal=]|date=2014|volume=21|issue=4|pages=304–23|doi=10.1097/MJT.0b013e318293b09b|pmid=23782759}}</ref> |
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Research suggests that methylglyoxal contained in honey does not cause an increased formation of advanced glycation end products (AGEs) in healthy persons.<ref>{{cite journal |vauthors=Wallace A, Eady S, Miles M, Martin H, McLachlan A, Rodier M, Willis J, Scott R, Sutherland J |title=Demonstrating the safety of manuka honey UMF® 20+ in a human clinical trial with healthy individuals |journal=Br J Nutr |volume=103 |issue=7 |pages=1023–8 |date=April 2010 |pmid=20064284 |doi=10.1017/S0007114509992777 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Degen J, Vogel M, Richter D, Hellwig M, Henle T |title=Metabolic transit of dietary methylglyoxal |journal=J Agric Food Chem |volume=61 |issue=43 |pages=10253–60 |date=October 2013 |pmid=23451712 |doi=10.1021/jf304946p }}</ref> |
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==See also== |
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* ] |
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** ], methylglyoxal can be classified as an 1,2-dicarbonyl |
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==References== |
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==References== |
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{{reflist}} |
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{{GABA receptor modulators}} |
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{{Transient receptor potential channel modulators}} |
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