Methylglyoxal

Methylglyoxal
IUPAC name 2-oxopropanal
Identifiers
CAS number	78-98-8 Y
PubChem	880
ChemSpider	857 Y
UNII	722KLD7415 Y
DrugBank	DB03587
KEGG	C00546 Y
MeSH	Methylglyoxal
ChEBI	CHEBI:17158 N
ChEMBL	CHEMBL170721 Y
Jmol-3D images	Image 1
SMILES CC(=O)C=O
InChI InChI=1S/C3H4O2/c1-3(5)2-4/h2H,1H3 Y Key: AIJULSRZWUXGPQ-UHFFFAOYSA-N Y InChI=1/C3H4O2/c1-3(5)2-4/h2H,1H3 Key: AIJULSRZWUXGPQ-UHFFFAOYAZ
Properties
Molecular formula	C3H4O2
Molar mass	72.0627
Related compounds
Related ketones, aldehydes	glyoxal propionaldehyde propanedial acetone diacetyl acetylacetone
Related compounds	glyoxylic acid pyruvic acid acetoacetic acid
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Methylglyoxal, also called pyruvaldehyde or 2-oxopropanal (CH₃-CO-CH=O or C₃H₄O₂) is the aldehyde form of pyruvic acid. It has two carbonyl groups, so it is a dicarbonyl compound. Methylglyoxal is both an aldehyde and a ketone.

In organisms, methylglyoxal is formed as a side-product of several metabolic pathways.^[1] It may form from 3-amino acetone, which is an intermediate of threonine catabolism, as well as through lipid peroxidation. However, the most important source is glycolysis. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate and dihydroxyacetone phosphate, two intermediates of glycolysis. Since methylglyoxal is highly cytotoxic, the body developed several detoxification mechanisms. One of these is the glyoxalase system. Methylglyoxal reacts with glutathione to form a hemithioacetal. This is converted into S-D-lactoyl-glutathione by glyoxalase I,^[2] and then further metabolised into D-lactate by glyoxalase II.^[3]

Why methylglyoxal is produced remains unknown, but several articles indicate it is involved in the formation of advanced glycation endproducts (AGEs). In fact, methylglyoxal is proven to be the most important glycation agent (forming AGEs).^[4] In this process, methylglyoxal reacts with free amino groups of lysine and arginine and with thiol groups of cysteine, forming AGEs. Recent research has identified heat shock protein 27 (Hsp27) as a specific target of posttranslational modification by methylglyoxal in human metastatic melanoma cells.^[5] Other glycation agents include the reducing sugars:

• glucose, the sugar that stores energy
• galactose, a part of milk sugar (lactose)
• allose, an all-cis hexose carried into the cell by special proteins
• ribose, a component of RNA.

Due to increased blood glucose levels, methylglyoxal has higher concentrations in diabetics, and has been linked to arterial atherogenesis. Damage by methylglyoxal to low-density lipoprotein though glycation causes a fourfold increase of atherogenesis in diabetics.^[6]

References

1. ^ Inoue Y, Kimura A (1995). "Methylglyoxal and regulation of its metabolism in microorganisms". Adv. Microb. Physiol. 37: 177–227. doi:10.1016/S0065-2911(08)60146-0. PMID 8540421. 
2. ^ Thornalley PJ (2003). "Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation". Biochem. Soc. Trans. 31 (Pt 6): 1343–8. doi:10.1042/BST0311343. PMID 14641060. http://www.biochemsoctrans.org/bst/031/1343/bst0311343.htm. 
3. ^ Vander Jagt DL (1993). "Glyoxalase II: molecular characteristics, kinetics and mechanism". Biochem. Soc. Trans. 21 (2): 522–7. PMID 8359524. 
4. ^ Shinohara M; Thornalley, PJ; Giardino, I; Beisswenger, P; Thorpe, SR; Onorato, J; Brownlee, M (1998). "Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis.". J Clin Invest. 101 (5): 1142–7. doi:10.1172/JCI119885. PMC 508666. PMID 9486985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=508666. 
5. ^ Bair WB 3rd, Cabello CM, Uchida K, Bause AS, Wondrak GT (April 2010). "GLO1 overexpression in human malignant melanoma". Melanoma Res 20 (2): 85–96. doi:10.1097/CMR.0b013e3283364903. PMC 2891514. PMID 20093988. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2891514. 
6. ^ Rabbani N; Godfrey, L; Xue, M; Shaheen, F; Geoffrion, M; Milne, R; Thornalley, PJ (2011 May 26). "Glycation of LDL by methylglyoxal increases arterial atherogenicity. A possible contributor to increased risk of cardiovascular disease in diabetes.". Diabetes. doi:10.2337/db11-0085. PMID 21617182. 

See also

• Manuka