Methylglyoxal (MGO) is the

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The s ...

with the formula CH₃C(O)CHO. It is a reduced derivative of

pyruvic acid 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 ac ...

. It is a reactive compound that is implicated in the biology of

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

. Methylglyoxal is produced industrially by degradation of carbohydrates using overexpressed methylglyoxal synthase.

Chemical structure

Gaseous methylglyoxal has two

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. A compound containing a ...

groups, an

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 grou ...

and a

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

. In the presence of water, it exists as hydrates and

oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...

s. The formation of these hydrates is indicative of the high reactivity of MGO, which is relevant to its biological behavior.

Biochemistry

Biosynthesis and biodegradation

In organisms, methylglyoxal is formed as a side-product of several

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical rea ...

s. Methylglyoxal mainly arises as side products of

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) ...

involving

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 ...

and

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.; Co ...

. It is also thought to arise via the degradation of acetone and threonine. Illustrative of the myriad pathways to MGO,

aristolochic acid Aristolochic acids () are a family of carcinogenic, mutagenic, and nephrotoxic phytochemicals commonly found in the flowering plant family Aristolochiaceae (birthworts). Aristolochic acid (AA) I is the most abundant one. The family Aristolochiace ...

caused 12-fold increase of methylglyoxal from 18 to 231 μg/mg of kidney protein in poisoned mice. It may form from 3-aminoacetone, which is an intermediate of

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

catabolism, as well as through

lipid peroxidation Lipid peroxidation is the chain of reactions of 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 chai ...

. However, the most important source is

. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate and

(DHAP), two intermediates of glycolysis. This conversion is the basis of a potential biotechnological route to the commodity chemical

1,2-propanediol Propylene glycol ( IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. Containing two alcohol groups, it is classed as a diol. It is ...

. Since methylglyoxal is highly

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cel ...

, several detoxification mechanisms have evolved. One of these is the

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. This system has been studied in both bacteria and eukaryotes. This deto ...

. Methylglyoxal is detoxified by

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, per ...

. Glutathione reacts with methylglyoxal to give a hemithioacetal, which converted into ''S''--lactoyl-glutathione by

glyoxalase I The enzyme lactoylglutathione lyase (EC 4.4.1.5, also known as glyoxalase I) catalyzes the isomerization of hemithioacetal adducts, which are formed in a spontaneous reaction between a glutathionyl group and aldehydes such as methylglyoxal. :(' ...

. This thioester is hydrolyzed to -lactate by glyoxalase II.

Biochemical function

Methylglyoxal is involved in the formation of advanced glycation endproducts (AGEs). In this process, methylglyoxal reacts with free amino groups of

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −CO ...

and

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the a ...

and with thiol groups of

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometim ...

forming AGEs. Histones are also heavily susceptible to modification by methylglyoxal and these modifications are elevated in breast cancer. Argpyrimidine Hydroimidazolone

Biomedical aspects

Due to increased blood glucose levels, methylglyoxal has higher concentrations in diabetics and has been linked to arterial

atherogenesis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...

. Damage by methylglyoxal to

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall dens ...

through glycation causes a fourfold increase of atherogenesis in diabetics. Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness in

diabetic neuropathy Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...

Occurrence, other

Methylglyoxal is a component of some kinds of honey, including mānuka honey; it appears to have activity against ''

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Es ...

'' and '' S. aureus'' and may help prevent formation of

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular p ...

s formed by '' P. aeruginosa ''. Research suggests that Methylglyoxal contained in honey does not cause an increased formation of advanced glycation end products (AGEs) in healthy persons.

References

{{Authority control Aldehydes Endogenous aldehydes GABAA receptor agonists Metabolism Conjugated ketones