Methylglyoxal pathway
Encyclopedia
The methylglyoxal pathway is an offshoot of glycolysis
found in some prokaryote
s, which converts glucose
into methylglyoxal
and then into pyruvate. However unlike glycolysis the methylglyoxal pathway does not produce adenosine triphosphate
, 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
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 is activated by the increased intercellular uptake of carbon containing molecules such as glucose
, glucose-6-phosphate
, lactate
, or glycerol
. Methylglyoxal is formed from dihydroxyacetone phosphate (DHAP) by the enzyme methylglyoxal synthase
, giving off a phosphate group.
Methylglyoxal is then converted into two different products, either D-lactate, and L-lactate. Methylglyoxal reductase and aldehyde dehydrogenase
convert methylglyoxal into lactaldehyde
and, eventually, L-lactate. If methylglyoxal enters the glyoxylase pathway, it is converted into lactoylguatathione and eventually D-lactate. Both D-lactate, and L-lactate are then converted into pyruvate. The pyruvate that is created most often goes on to enter the Krebs cycle (Weber 711-13).
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
(GAP) into DHAP. The usual pathway converting GAP to pyruvate starts with the enzyme glyceraldehyde 3-phosphate dehydrogenase
(Weber 711-13). Low phosphate levels inhibit GAP dehydrogenase; GAP is instead converted into DHAP by triosephosphate isomerase (Wikipedia Triosephosphate isomerase). Again, increased levels of DHAP activate methylglyoxal synthase and methylglyoxal production (Weber 711-13).
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
found in some prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s, which converts glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
into methylglyoxal
Methylglyoxal
Methylglyoxal, also called pyruvaldehyde or 2-oxopropanal 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....
and then into pyruvate. However unlike glycolysis the methylglyoxal pathway does not produce adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, 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
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R 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
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, glucose-6-phosphate
Glucose-6-phosphate
Glucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cells as the vast majority of glucose entering a cell will become phosphorylated in this way....
, lactate
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
, or glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...
. Methylglyoxal is formed from dihydroxyacetone phosphate (DHAP) by the enzyme methylglyoxal synthase
Methylglyoxal synthase
In enzymology, a methylglyoxal synthase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, glycerone phosphate, and two products, methylglyoxal and phosphate....
, 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 dehydrogenase
Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes.- Function :Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids, which leave the liver and are metabolized by the body’s muscle and heart...
convert methylglyoxal into lactaldehyde
Lactaldehyde
Lactaldehyde is an intermediate in the methylglyoxal metabolic pathway. Methylglyoxal is converted to D-lactaldehyde by glycerol dehydrogenase . Lactaldehyde is then oxidized to lactic acid by aldehyde dehydrogenase....
and, eventually, L-lactate. If methylglyoxal enters the glyoxylase pathway, it is converted into lactoylguatathione and eventually D-lactate. Both D-lactate, and L-lactate are then converted into pyruvate. The pyruvate that is created most often goes on to enter the Krebs cycle (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 methylglyoxal synthaseMethylglyoxal synthase
In enzymology, a methylglyoxal synthase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, glycerone phosphate, and two products, methylglyoxal and phosphate....
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
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...
(GAP) into DHAP. The usual pathway converting GAP to pyruvate starts with the enzyme glyceraldehyde 3-phosphate dehydrogenase
Glyceraldehyde 3-phosphate dehydrogenase
Glyceraldehyde 3-phosphate dehydrogenase is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules...
(Weber 711-13). Low phosphate levels inhibit GAP dehydrogenase; GAP is instead converted into DHAP by triosephosphate isomerase (Wikipedia Triosephosphate isomerase). Again, increased levels of DHAP activate methylglyoxal synthase and methylglyoxal production (Weber 711-13).