Methylglyoxal
| Methylglyoxal | |
|---|---|
 |
 |
| IUPAC name 2-oxopropanal | |
| Identifiers | |
| CAS number | 78-98-8  |
| PubChem | 880 |
| ChemSpider | 857 |
| UNII | 722KLD7415 |
| DrugBank | DB03587 |
| KEGG | C00546 |
| MeSH | Methylglyoxal |
| ChEBI | CHEBI:17158  |
| ChEMBL | CHEMBL170721 |
| Jmol-3D images | Image 1 |
| |
| |
| Properties | |
| Molecular formula | C3H4O2 |
| Molar mass | 72.06 g mol−1 |
| Appearance | Yellow liquid |
| Density | 1.046 g·cm-3 |
| Boiling point | 72 °C |
| Related compounds | |
| Related ketones, aldehydes | glyoxal propionaldehyde propanedial acetone diacetyl acetylacetone |
| Related compounds | glyoxylic acid pyruvic acid acetoacetic acid |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 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-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. 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 metabolized into D-lactate by glyoxalase II.[3]
Why methylglyoxal is produced remains unknown, but research indicates it may be involved in the formation of advanced glycation endproducts (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 through glycation causes a fourfold increase of atherogenesis in diabetics.[6]
Methylglyoxal has been suggested to be a better marker than carboxymethyllysine (CML) for investigating the association between AGEs with adverse health outcomes.
Recently one mechanism of activity in humans of methylglyoxal has been identified.[7][8] Methylglyoxal binds directly to the nerves responsible for pain registration and by that increases pain sensation.
Methylglyoxal is the main active component of manuka honey and accounts for the majority of this honey's antimicrobial activity.[9]
References
- ↑ 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.
- ↑ 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.
- ↑ Vander Jagt DL (1993). "Glyoxalase II: molecular characteristics, kinetics and mechanism". Biochem. Soc. Trans. 21 (2): 522–7. PMID 8359524.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Spektrum: Diabetische Neuropathie: Methylglyoxal verstärkt den Schmerz: DAZ.online. Deutsche-apotheker-zeitung.de (2012-05-21). Retrieved on 2012-06-11.
- ↑ 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. doi:10.1038/nm.2750.
- ↑ Kwakman PHS, te Velde AA, de Boer L, Vandenbroucke-Grauls CMJE, Zaat SAJ (2011). "Two major medicinal honeys have different mechanisms of bactericidal activity". PLoS ONE 6 (3): e17709. doi:10.1371/journal.pone.0017709. PMC 3048876. PMID 21394213.