Methylglyoxal (MGO) is the
organic compound with the formula CH3C(O)CHO. It is a reduced derivative of
pyruvic acid. It is a reactive compound that is implicated in the biology of
diabetes. Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressed
methylglyoxal synthase.[1]
Chemical structure
Gaseous methylglyoxal has two
carbonyl groups, an
aldehyde and a
ketone. In the presence of water, it exists as hydrates and
oligomers. The formation of these hydrates is indicative of the high reactivity of MGO, which is relevant to its biological behavior.[2]
Biochemistry
Biosynthesis and biodegradation
In organisms, methylglyoxal is formed as a side-product of several
metabolic pathways.[3] Methylglyoxal mainly arises as side products of
glycolysis involving
glyceraldehyde-3-phosphate and
dihydroxyacetone phosphate. It is also thought to arise via the degradation of
acetone and
threonine.[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 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 (DHAP), two intermediates of glycolysis. This conversion is the basis of a potential biotechnological route to the commodity chemical
1,2-propanediol.[6]
Methylglyoxal is involved in the formation of
advanced glycation end products (AGEs).[4] In this process, methylglyoxal reacts with free amino groups of
lysine and
arginine and with thiol groups of
cysteine forming AGEs.
Histones are also heavily susceptible to modification by methylglyoxal and these modifications are elevated in breast cancer.[9][10]
Due to increased blood glucose levels, methylglyoxal has higher concentrations in
diabetics and has been linked to
arterialatherogenesis. Damage by methylglyoxal to
low-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 in
diabetic 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]
^
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