Methylglyoxal (MGO) is theorganic compound with the formula CH3C(O)CHO. It is a reduced derivative ofpyruvic acid. It is a reactive compound that is implicated in the biology ofdiabetes. Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressedmethylglyoxal synthase.[1]
Gaseous methylglyoxal has twocarbonyl groups: analdehyde and aketone. In the presence of water, it exists as hydrates andoligomers. The formation of these hydrates is indicative of the high reactivity of MGO, which is relevant to its biological behavior.[2]
In organisms, methylglyoxal is formed as a side-product of severalmetabolic pathways.[3] Methylglyoxal mainly arises as side products ofglycolysis involvingglyceraldehyde-3-phosphate anddihydroxyacetone phosphate. It is also thought to arise via the degradation ofacetone andthreonine.[4] Illustrative of the myriad pathways to MGO,aristolochic acid caused 12-fold increase of methylglyoxal from 18 to 231 μg/mg of kidney protein in poisoned mice.[5] It may form from3-aminoacetone, which is an intermediate of threoninecatabolism, as well as throughlipid peroxidation. However, the most important source isglycolysis. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate anddihydroxyacetone phosphate (DHAP), two intermediates of glycolysis. This conversion is the basis of a potential biotechnological route to the commodity chemical1,2-propanediol.[6]
Methylglyoxal is involved in the formation ofadvanced glycation end products (AGEs).[4] In this process, methylglyoxal reacts with free amino groups oflysine andarginine and with thiol groups ofcysteine forming AGEs.Argpyrimidine is one example.Histones are also heavily susceptible to modification by methylglyoxal and these modifications are elevated in breast cancer.[9][10]
AGEs derived from the action of methylglyoxal on arginine.[11]
Due to increased blood glucose levels, methylglyoxal has higher concentrations indiabetics and has been linked toarterialatherogenesis. Damage by methylglyoxal tolow-density lipoprotein through glycation causes a fourfold increase of atherogenesis in diabetics.[13] Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness indiabetic neuropathy.[14][15]
Research suggests that methylglyoxal contained in honey does not cause an increased formation of advanced glycation end products (AGEs) in healthy persons.[17][18]
^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 (20):6318–23.Bibcode:2006EnST...40.6318L.doi:10.1021/es060810w.PMID17120559.
^abBellier, Justine; Nokin, Marie-Julie; Lardé, Eva; Karoyan, Philippe; Peulen, Olivier; Castronovo, Vincent; Bellahcène, Akeila (2019). "Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer".Diabetes Research and Clinical Practice.148:200–211.doi:10.1016/j.diabres.2019.01.002.PMID30664892.S2CID58631777.
^Li, YC; Tsai, SH; Chen, SM; Chang, YM; Huang, TC; Huang, YP; Chang, CT; Lee, JA (2012). "Aristolochic acid-induced accumulation of methylglyoxal and Nε-(carboxymethyl)lysine: an important and novel pathway in the pathogenic mechanism for aristolochic acid nephropathy".Biochem Biophys Res Commun.423 (4):832–7.doi:10.1016/j.bbrc.2012.06.049.PMID22713464.
^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.PMID14641060.
^abRicharme 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
