The methylglyoxal pathway is an offshoot of glycolysis found in some

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...

s, which converts

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, usi ...

into

methylglyoxal 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 ...

and then into

pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic aci ...

. However unlike glycolysis the methylglyoxal pathway does not produce

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...

, ATP. The pathway is named after the substrate methylglyoxal which has three carbons and two carbonyl groups located on the 1st carbon and one on the 2nd carbon. Methylglyoxal is, however, a reactive

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...

that is very toxic to cells, it can inhibit growth in ''E. coli'' at milimolar concentrations. The excessive intake of glucose by a cell is the most important process for the activation of the methylglyoxal pathway.

The Methylglyoxal pathway

The methylglyoxal pathway is activated by the increased intercellular uptake of carbon containing molecules such as

glucose-6-phosphate Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this w ...

lactate Lactate may refer to: * Lactation, the secretion of milk from the mammary glands * Lactate, the conjugate base of lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with ...

, or

glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids know ...

. Methylglyoxal is formed from

dihydroxyacetone phosphate Dihydroxyacetone phosphate (DHAP, also glycerone phosphate in older texts) is the anion with the formula HOCH2C(O)CH2OPO32-. This anion is involved in many metabolic pathways, including the Calvin cycle in plants and glycolysis.Nelson, D. L.; C ...

(DHAP) by the enzyme

methylglyoxal synthase The enzyme methylglyoxal synthase (EC 4.2.3.3) catalyzes the chemical reaction :glycerone phosphate \rightleftharpoons 2-oxopropanalCommonly known as methylglyoxal + phosphate Attempts to observe reversibility of this reaction have been unsucc ...

, giving off a phosphate group. Methylglyoxal is then converted into two different products, either D-lactate, and L-lactate. Methylglyoxal reductase and

aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...

convert methylglyoxal into

lactaldehyde Lactaldehyde is an intermediate in the methylglyoxal metabolic pathway. Methylglyoxal is converted to D-lactaldehyde by glycerol dehydrogenase (gldA). Lactaldehyde is then oxidized to lactic acid by aldehyde dehydrogenase. Structure Lactalde ...

and, eventually, L-lactate. If methylglyoxal enters the

glyoxylase pathway The glyoxalase system is a set of enzymes that carry out the detoxification of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism. This system has been studied in both bacteria and eukaryotes. This detox ...

, it is converted into lactoylguatathione and eventually D-lactate. Both D-lactate, and L-lactate are then converted into

. The pyruvate that is created most often goes on to enter the

Krebs cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

Weber
711–13).

Enzymes and regulation

The potentially hazardous effects of methylglyoxal require regulation of the reactions with this substrate. Synthesis of methylglyoxal is regulated by levels of DHAP and phosphate concentrations. High concentrations of DHAP encourage

to produce methylglyoxal, while high phosphate concentrations inhibit the enzyme, and therefore the production of more methylglyoxal. The enzyme triose phosphate isomerase affects the levels of DHAP by converting

glyceraldehyde 3-phosphate Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central pathways of all organisms.Nelson, D ...

(GAP) into DHAP. The usual pathway converting GAP to pyruvate starts with the enzyme

glyceraldehyde 3-phosphate dehydrogenase Glyceraldehyde 3-phosphate dehydrogenase (abbreviated GAPDH) () is an enzyme of about 37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long establish ...

Weber
711–13). Low phosphate levels inhibit GAP dehydrogenase; GAP is instead converted into DHAP by

triosephosphate isomerase Triose-phosphate isomerase (TPI or TIM) is an enzyme () that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate. TPI plays an important role in glycolysis and ...

. Again, increased levels of DHAP activate methylglyoxal synthase and methylglyoxal production
Weber
711–13).

The oscillation of Methylglyoxal concentration in feast concentrations

Jan Weber, Anke Kayser, and Ursula Rinas, performed an experiment to test what happened to the methylglyoxal pathway when ''E. coli'' was in the presence of a constantly high concentration of glucose. The concentration of methylglyoxal increased until it reached 20 μmol. Methylglyoxal concentration then began to decrease, once it reached this level. The decrease in the concentration of methylglyoxal was connected to the drop in respiratory activity. When respiration activity increased the concentration of methylglyoxal increased again, until it reached the 20 μmol concentration
Weber
714–15).

Why does the Methylglyoxal pathway exist?

This pathway does not produce any ATP, this pathway does not replace glycolysis, it runs simultaneously to glycolysis and is only initiated with an increased concentration of sugar phosphates. One believed purpose of the methylglyoxal pathway is to help release the stress of elevated sugar phosphate concentration. Also when methylglyoxal is formed from DHAP, an inorganic phosphate is given off which can be used to replenish a low concentration of needed inorganic phosphate. The methylglyoxal pathway is a rather dangerous tactic, both because less energy is produced and a toxic compound, methylglyoxal is formed.
Weber
715).

References

{{Reflist Weber, Jan, Anke Kayser, and Ursula Rinas. Metabolic Flux Analysis of Escherichia Coli In. Vers. 151: 707-716. 6 Dec. 2004. Microbiology. 10 Apr. 2007 . Saadat, D., Harrison, D.H.T. "Methylglyoxal Synthase From ''Escherichia Coli''." RCSB Protein Data Base. 24 Apr. 2007. RCSB Protein Data Base. 25 Apr. 2007 . "Methylglyoxal Synthase From Escherichia Coli." RCSB Protein Data Base. 24 Apr. 2007. RCSB Protein Data Base. 25 Apr. 2007 . Yun, M., C.-G. Park, J.-Y Kim, and H.-W. Park. "Structural Anayysis of Glyeraldehyde 3-Phosphate Dehydrogenase from ''Escherichia coli: Direct Evidence for Substrate Binding and Cofactor-Induced Confromational Changes.'' RCSB Protein Data Base. 24 Apr. 2007. RCSB Protein Data Base. 30 Apr. 2007 . Cellular respiration