Methylglyoxal

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. It is a reduced derivative of pyruvic acid. 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. It is a reduced derivative of pyruvic acid. Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressed methylglyoxal synthase. In organisms, methylglyoxal is formed as a side-product of several metabolic pathways. 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. Aristolochic acid caused 12-fold increase of methylglyoxal from 18 to 231 μg/mg of kidney protein in poisoned mice. Since methylglyoxal is highly cytotoxic, several detoxification mechanisms have evolved. One of these is the glyoxalase system. Methylglyoxal is detoxified by glutathione. Glutathione reacts with methylglyoxal to give a hemithioacetal, which converted into S-D-lactoyl-glutathione by glyoxalase I. This thioester is hydrolyzed to D-lactate by glyoxalase II. The proximate and ultimate causes for biological methylglyoxal production remain unknown, but it may be involved in the formation of advanced glycation endproducts (AGEs). 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. Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness in diabetic neuropathy. Other glycation agents include the reducing sugars: 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.