Methylglyoxal

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Methylglyoxal
Skeletal formula
Ball-and-stick model of methylglyoxal
Names
IUPAC name
2-Oxopropanal
Other names
Pyruvaldehyde
Identifiers
  • (hydrate: 1186-47-6) 78-98-8 (hydrate: 1186-47-6) ☒N
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:17158 ☒N
ChEMBL
  • ChEMBL170721 ☑Y
ChemSpider
  • 857 ☑Y
DrugBank
  • DB03587 ☒N
ECHA InfoCard 100.001.059
  • 6303
KEGG
  • C00546 ☑Y
MeSH Methylglyoxal
PubChem CID
  • 880
UNII
  • 722KLD7415 ☑Y
Properties
C3H4O2
Molar mass 72.06 g·mol−1
Appearance Yellow liquid
Density 1.046 g/cm3
Boiling point 72 °C (162 °F; 345 K)
Related compounds
Related ketones, aldehydes
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is ☑Y☒N ?)
Infobox references

Methylglyoxal, also called pyruvaldehyde or 2-oxopropanal, is the organic compound with the formula CH3C(O)CHO. Gaseous methylglyoxal has two carbonyl groups, an aldehyde and a ketone but in the presence of water, it exists as hydrates and oligomers.[1] It is a reduced derivative of pyruvic acid.

Industrial production and biosynthesis

Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressed methylglyoxal synthase.[2]

In organisms, methylglyoxal is formed as a side-product of several metabolic pathways.[3] It may form from 3-aminoacetone, 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.

Aristolochic acid caused 12-fold increase of methylglyoxal from 18 to 231 μg/mg of kidney protein in poisoned mice.[4]

Biochemistry

Since methylglyoxal is highly cytotoxic, several detoxification mechanisms have evolved. One of these is the glyoxalase system. Methylglyoxal is detoxified by glutathione. Glutathione react with methylglyoxal to give a hemithioacetal, which converted into S-D-lactoyl-glutathione by glyoxalase I.[5] This thioester is hydrolyzedto D-lactate by glyoxalase II.[6]

The proximate and ultimate causes for biological methylglyoxal production remain unknown, but it may be involved in the formation of advanced glycation endproducts (AGEs).[7] In this process, methylglyoxal reacts with free amino groups of lysine and arginine and with thiol groups of cysteine forming AGEs. The heat shock protein 27 (Hsp27) is a specific target of posttranslational modification by methylglyoxal in human metastatic melanoma cells.[8]

Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness in diabetic neuropathy.[9][10]

Other glycation agents include the reducing sugars:

Natural occurrence

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 through glycation causes a fourfold increase of atherogenesis in diabetics.[11]

Although methylglyoxal has been shown to increase carboxymethyllysine levels,[12] methylglyoxal has been suggested to be a better marker for investigating the association between AGEs with adverse health outcomes.

Methylglyoxal is a component of some kinds of honey, including manuka honey; it appears to have activity against E. coli and S. aureus and may help prevent formation of biofilms formed by P. aeruginosa .[13]

References

  1. ^ Loeffler Kirsten W.; Koehler Charles A.; Paul Nichole M.; De Haan David O. (2006). "Oligomer Formation in Evaporating Aqueous Glyoxal and Methyl Glyoxal Solutions". Environmental Science & Technology. 40: 6318–6323. doi:10.1021/es060810w.
  2. ^ Frieder W. Lichtenthaler "Carbohydrates as Organic Raw Materials" in Ullmann's Encyclopedia of Industrial Chemistry 2010, Wiley-VCH, Weinheim. doi: 10.1002/14356007.n05_n07
  3. ^ Inoue Y, Kimura A (1995). "Methylglyoxal and regulation of its metabolism in microorganisms". Adv. Microb. Physiol. Advances in Microbial Physiology. 37: 177–227. doi:10.1016/S0065-2911(08)60146-0. ISBN 978-0-12-027737-7. PMID 8540421.
  4. ^ Li, Biochem Biophys Res Commun 423:832 2012 PMID 22713464 doi: 10.1016/j.bbrc.2012.06.049
  5. ^ 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.
  6. ^ Vander Jagt DL (1993). "Glyoxalase II: molecular characteristics, kinetics and mechanism". Biochem. Soc. Trans. 21 (2): 522–7. PMID 8359524.
  7. ^ 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.
  8. ^ 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.
  9. ^ Spektrum: Diabetische Neuropathie: Methylglyoxal verstärkt den Schmerz: DAZ.online. Deutsche-apotheker-zeitung.de (2012-05-21). Retrieved on 2012-06-11.
  10. ^ Bierhaus, Angelika; Fleming, Thomas; Stoyanov, Stoyan; Leffler, Andreas; Babes, Alexandru; Neacsu, Cristian; Sauer, Susanne K; Eberhardt, Mirjam; et al. (2012). "Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy". Nature Medicine. 18 (6): 926–33. doi:10.1038/nm.2750. PMID 22581285.
  11. ^ Rabbani N; Godfrey, L; Xue, M; Shaheen, F; Geoffrion, M; Milne, R; Thornalley, PJ (May 26, 2011). "Glycation of LDL by methylglyoxal increases arterial atherogenicity. A possible contributor to increased risk of cardiovascular disease in diabetes". Diabetes. 60 (7): 1973–80. doi:10.2337/db11-0085. PMC 3121424. PMID 21617182.
  12. ^ Cai, W., Uribarri, J., Zhu, L., Chen, X., Swamy, S., Zhao, Z., Grosjean, F., Simonaro, C., Kuchel, G. A., Schnaider-Beeri, M., Woodward, M., Striker, G. E., and Vlassara, H. (2014) Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. PNAS 111.
  13. ^ Israili, ZH (2014). "Antimicrobial properties of honey". American Journal of Therapeutics. 21 (4): 304–23. doi:10.1097/MJT.0b013e318293b09b. PMID 23782759.
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