Methylglyoxal
Encyclopedia
Methylglyoxal, also called pyruvaldehyde or 2-oxopropanal (CH3-CO-CH=O or C3H4O2) 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
.
In organisms, methylglyoxal is formed as a side-product of several metabolic pathway
s. It may form from 3-amino acetone
, 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, two intermediates of glycolysis. Since methylglyoxal is highly cytotoxic
, the body developed several detoxification mechanisms. One of these is the glyoxalase system
. Methylglyoxal reacts with glutathione
to form a hemithioacetal. This is converted into S-D-lactoyl-glutathione by glyoxalase I, and then further metabolised into D-lactate by glyoxalase II.
Why methylglyoxal is produced remains unknown, but several articles indicate it is involved in the formation of advanced glycation endproduct
s (AGEs). In fact, methylglyoxal is proven to be the most important glycation agent (forming AGEs). In this process, methylglyoxal reacts with free amino groups of lysine
and arginine
and with thiol groups of cysteine
, forming AGEs. Recent research has identified heat shock protein 27 (Hsp27
) as a specific target of posttranslational modification by methylglyoxal in human metastatic melanoma
cells.
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 though glycation causes a fourfold increase of atherogenesis in diabetics.
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....
form of pyruvic acid
Pyruvic acid
Pyruvic acid is an organic acid, a ketone, as well as the simplest of the alpha-keto acids. The carboxylate ion of pyruvic acid, CH3COCOO−, is known as pyruvate, and is a key intersection in several metabolic pathways....
. It has two carbonyl groups, so it is a dicarbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
compound. Methylglyoxal is both an aldehyde and a ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
.
In organisms, methylglyoxal is formed as a side-product of several metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
s. It may form from 3-amino acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, which is an intermediate of threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
catabolism, as well as through lipid peroxidation
Lipid peroxidation
Lipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism...
. However, the most important source is glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate and dihydroxyacetone phosphate, two intermediates of glycolysis. Since methylglyoxal is highly cytotoxic
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
, the body developed several detoxification mechanisms. One of these is the glyoxalase system
Glyoxalase system
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...
. Methylglyoxal reacts with glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
to form a hemithioacetal. This is converted into S-D-lactoyl-glutathione by glyoxalase I, and then further metabolised into D-lactate by glyoxalase II.
Why methylglyoxal is produced remains unknown, but several articles indicate it is involved in the formation of advanced glycation endproduct
Advanced glycation endproduct
An advanced glycation end-product is the result of a chain of chemical reactions after an initial glycation reaction. The intermediate products are known, variously, as Amadori, Schiff base and Maillard products, named after the researchers who first described them. An advanced glycation...
s (AGEs). In fact, methylglyoxal is proven to be the most important glycation agent (forming AGEs). In this process, methylglyoxal reacts with free amino groups of lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
and arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
and with thiol groups of cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
, forming AGEs. Recent research has identified heat shock protein 27 (Hsp27
Hsp27
Heat shock protein 27 also known as heat shock protein beta-1 is a protein that in humans is encoded by the HSPB1 gene.Hsp27 is a chaperone of the sHsp group among ubiquitin, α-crystallin, Hsp20 and others...
) as a specific target of posttranslational modification by methylglyoxal in human metastatic melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
cells.
Other glycation
Glycation
Glycation is the result of the bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. All blood sugars are reducing molecules. Glycation may occur either inside the body or outside the body...
agents include the reducing sugars:
- glucoseGlucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, the sugar that stores energyEnergyIn physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems... - galactoseGalactoseGalactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
, a part of milk sugar (lactoseLactoseLactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
) - alloseAlloseAllose is an aldohexose sugar. It is a rare monosaccharide that has been isolated from the leaves of the African shrub Protea rubropilosa. It is soluble in water and practically insoluble in methanol.Allose is a C-3 epimer of glucose....
, an all-cis hexoseHexoseIn organic chemistry, a hexose is a monosaccharide with six carbon atoms, having the chemical formula C6H12O6. Hexoses are classified by functional group, with aldohexoses having an aldehyde at position 1, and ketohexoses having a ketone at position 2....
carried into the cellCell (biology)The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
by special proteins - riboseRiboseRibose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....
, a component of RNARNARibonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
.
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 though glycation causes a fourfold increase of atherogenesis in diabetics.