Methylglyoxal

Last updated
Methylglyoxal
Skeletal formula Pyruvaldehyde.svg
Skeletal formula
Methylglyoxal molecule ball.png
Names
Preferred IUPAC name
2-Oxopropanal
Other names
Pyruvaldehyde
Identifiers
3D model (JSmol)
3DMet
906750
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.001.059 OOjs UI icon edit-ltr-progressive.svg
KEGG
MeSH Methylglyoxal
PubChem CID
UNII
  • InChI=1S/C3H4O2/c1-3(5)2-4/h2H,1H3 Yes check.svgY
    Key: AIJULSRZWUXGPQ-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C3H4O2/c1-3(5)2-4/h2H,1H3
    Key: AIJULSRZWUXGPQ-UHFFFAOYAZ
  • CC(=O)C=O
Properties
C3H4O2
Molar mass 72.063 g·mol−1
AppearanceYellow liquid
Density 1.046 g/cm3
Melting point 25 °C (77 °F; 298 K)
Boiling point 72 °C (162 °F; 345 K)
Hazards
GHS labelling:
GHS-pictogram-acid.svg GHS-pictogram-skull.svg GHS-pictogram-silhouette.svg
Danger
H290, H302, H315, H317, H318, H319, H335, H341
P201, P202, P234, P261, P264, P270, P271, P272, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P390, P403+P233, P404, P405, P501
Related compounds
Related ketones, aldehydes
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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 of carbohydrates using overexpressed methylglyoxal synthase. [1]

Contents

Chemical structure

Gaseous methylglyoxal has two carbonyl groups, an aldehyde and a ketone. In the presence of water, it exists as hydrates and oligomers. The formation of these hydrates is indicative of the high reactivity of MGO, which is relevant to its biological behavior. [2]

Biochemistry

Biosynthesis and biodegradation

In organisms, methylglyoxal is formed as a side-product of several metabolic pathways. [3] Methylglyoxal mainly arises as side products of glycolysis involving glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. It is also thought to arise via the degradation of acetone and threonine. [4] Illustrative of the myriad pathways to MGO, aristolochic acid caused 12-fold increase of methylglyoxal from 18 to 231 μg/mg of kidney protein in poisoned mice. [5] 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. [6]

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. [7] This thioester is hydrolyzed to D-lactate by glyoxalase II. [8]

Biochemical function

Methylglyoxal is involved in the formation of advanced glycation end products (AGEs). [4] In this process, methylglyoxal reacts with free amino groups of lysine and arginine and with thiol groups of cysteine forming AGEs. Histones are also heavily susceptible to modification by methylglyoxal and these modifications are elevated in breast cancer. [9] [10]

AGEs derived from the action of methylglyoxal on arginine. Argpyrimidine Hydroimidazolone.png
AGEs derived from the action of methylglyoxal on arginine.

DNA damages are induced by reactive carbonyls, principally methylglyoxal and glyoxal, at a frequency similar to that of oxidative DNA damages. [12] Such damage, referred to as DNA glycation, can cause mutation, breaks in DNA and cytotoxicity. [12] In humans, a protein DJ-1 (also named PARK7), has a key role in the repair of glycated DNA bases.

Biomedical aspects

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. [13] Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness in diabetic neuropathy. [14] [15]

Occurrence, other

Methylglyoxal is a component of some kinds of honey, including manuka honey; it appears to have activity against E. coli and S. aureus and may help prevent formation of biofilms formed by P. aeruginosa . [16]

Research suggests that methylglyoxal contained in honey does not cause an increased formation of advanced glycation end products (AGEs) in healthy persons. [17] [18]

See also

Related Research Articles

<span class="mw-page-title-main">Dicarbonyl</span> Molecule containing two adjacent C=O groups

In organic chemistry, a dicarbonyl is a molecule containing two carbonyl groups. Although this term could refer to any organic compound containing two carbonyl groups, it is used more specifically to describe molecules in which both carbonyls are in close enough proximity that their reactivity is changed, such as 1,2-, 1,3-, and 1,4-dicarbonyls. Their properties often differ from those of monocarbonyls, and so they are usually considered functional groups of their own. These compounds can have symmetrical or unsymmetrical substituents on each carbonyl, and may also be functionally symmetrical or unsymmetrical.

Glycation is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus.

Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease.

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. It is the phosphate ester of dihydroxyacetone.

<span class="mw-page-title-main">Triosephosphate isomerase</span> Enzyme involved in glycolysis

Triose-phosphate isomerase is an enzyme that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.

Glyoxal is an organic compound with the chemical formula OCHCHO. It is the smallest dialdehyde. It is a crystalline solid, white at low temperatures and yellow near the melting point (15 °C). The liquid is yellow, and the vapor is green.

The polyol pathway is a two-step process that converts glucose to fructose. In this pathway glucose is reduced to sorbitol, which is subsequently oxidized to fructose. It is also called the sorbitol-aldose reductase pathway.

<span class="mw-page-title-main">Lactoylglutathione lyase</span> Protein-coding gene in the species Homo sapiens

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.

The enzyme methylglyoxal synthase catalyzes the chemical reaction

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 detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly glyoxalase І, which catalyzes the isomerization of the spontaneously formed hemithioacetal adduct between glutathione and 2-oxoaldehydes into S-2-hydroxyacylglutathione. Secondly, glyoxalase ІІ hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione.

<span class="mw-page-title-main">HAGH</span> Protein-coding gene in the species Homo sapiens

Hydroxyacylglutathione hydrolase, mitochondrial is an enzyme that in humans is encoded by the HAGH gene.

<span class="mw-page-title-main">Diabetic cardiomyopathy</span> Medical condition

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure(HF), with accumulation of fluid in the lungs or legs. Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.

Pimagedine, also known as aminoguanidine, is an investigational drug for the treatment of diabetic nephropathy that is no longer under development as a drug. Pimagedine functions as an inhibitor of diamine oxidase and nitric oxide synthase. It acts to reduce levels of advanced glycation end products (AGEs) through interacting with 3-deoxyglucosone, glyoxal, methylglyoxal, and related dicarbonyls. These reactive species are converted to less reactive heterocycles by this condensation reaction.

<span class="mw-page-title-main">3-Deoxyglucosone</span> Chemical compound

3-Deoxyglucosone (3DG) is a sugar that is notable because it is a marker for diabetes. 3DG reacts with protein to form advanced glycation end-products (AGEs), which contribute to diseases such as the vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, inflammation, and aging.

<span class="mw-page-title-main">Hemithioacetal</span> Organosulfur compound of the form –CH(–OH)S–

In organic chemistry, hemithioacetals are organosulfur compounds with the general formula R−CH(−OH)−SR’. They are the sulfur analogues of the acetals, R−CH(−OH)−OR’, with an oxygen atom replaced by sulfur. Because they consist of four differing substituents on a single carbon, hemithioacetals are chiral. A related family of compounds are the dithiohemiacetals, with the formula R−CH(−SH)−SR’. Although they can be important intermediates, hemithioacetals are usually not isolated, since they exist in equilibrium with thiols and aldehydes.

Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.

<span class="mw-page-title-main">Argpyrimidine</span> Chemical compound

Argpyrimidine is an organic compound with the chemical formula C11H18N4O3. It is an advanced glycation end-product formed from arginine and methylglyoxal through the Maillard reaction. Argpyrimidine has been studied for its food chemistry purposes and its potential involvement in aging diseases and Diabetes Mellius.

Manju Ray was an Indian scientist specializing in Molecular Enzymology and Cancer Biochemistry. Her research has contributed significantly to the development of anticancer drugs and understanding the differentiation process of cells. Her interests include tumor biochemistry and molecular enzymology. She was awarded the Shanti Swarup Bhatnagar Prize for Science and Technology in the year 1989, being only the second woman to receive this award in the category 'Biological Sciences'.

<span class="mw-page-title-main">Reactive carbonyl species</span>

Reactive carbonyl species (RCS) are molecules with highly reactive carbonyl groups, and often known for their damaging effects on proteins, nucleic acids, and lipids. They are often generated as metabolic products. Important RCSs include 3-deoxyglucosone, glyoxal, and methylglyoxal. RCSs react with amines and thiol groups leading to advanced glycation endproducts (AGEs). AGE's are indicators of diabetes.

<span class="mw-page-title-main">Imidazolone</span> Class of chemical compounds

Imidazolinones or imidazolones are a family of heterocyclic compounds, the parents of which have the formula OC(NH)2(CH)2. Two isomers are possible, depending on the location of the carbonyl (CO) group. The NH groups are nonadjacent. A common route to imidazol-2-ones involves condensation of ureas and acyloins. Some are of interest in the pharmaceuticals. 4-Imidazolones arise from the condensation of amidines with 1,2-dicarbonyls such as glyoxal.

References

  1. ↑ Lichtenthaler, Frieder W. (2010). "Carbohydrates as Organic Raw Materials". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.n05_n07. ISBN   978-3527306732.
  2. ↑ Loeffler, Kirsten W.; Koehler, Charles A.; Paul, Nichole M.; De Haan, David O. (2006). "Oligomer Formation in Evaporating Aqueous Glyoxal and Methyl Glyoxal Solutions". Environmental Science & Technology. 40 (20): 6318–23. Bibcode:2006EnST...40.6318L. doi:10.1021/es060810w. PMID   17120559.
  3. ↑ Inoue Y, Kimura A (1995). "Methylglyoxal and regulation of its metabolism in microorganisms". Adv. Microb. Physiol. Advances in Microbial Physiology. 37: 177–227. doi:10.1016/S0065-2911(08)60146-0. ISBN   978-0-12-027737-7. PMID   8540421.
  4. 1 2 Bellier, Justine; Nokin, Marie-Julie; Lardé, Eva; Karoyan, Philippe; Peulen, Olivier; Castronovo, Vincent; Bellahcène, Akeila (2019). "Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer". Diabetes Research and Clinical Practice. 148: 200–211. doi:10.1016/j.diabres.2019.01.002. PMID   30664892. S2CID   58631777.
  5. ↑ Li, YC; Tsai, SH; Chen, SM; Chang, YM; Huang, TC; Huang, YP; Chang, CT; Lee, JA (2012). "Aristolochic acid-induced accumulation of methylglyoxal and Nε-(carboxymethyl)lysine: an important and novel pathway in the pathogenic mechanism for aristolochic acid nephropathy". Biochem Biophys Res Commun. 423 (4): 832–7. doi:10.1016/j.bbrc.2012.06.049. PMID   22713464.
  6. ↑ Sullivan, Carl J.; Kuenz, Anja; Vorlop, Klaus‐Dieter (2018). "Propanediols". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_163.pub2. ISBN   978-3527306732.
  7. ↑ Thornalley PJ (2003). "Glyoxalase I—structure, function and a critical role in the enzymatic defence against glycation". Biochem. Soc. Trans. 31 (Pt 6): 1343–8. doi:10.1042/BST0311343. PMID   14641060.
  8. ↑ Vander Jagt DL (1993). "Glyoxalase II: molecular characteristics, kinetics and mechanism". Biochem. Soc. Trans. 21 (2): 522–7. doi:10.1042/bst0210522. PMID   8359524.
  9. ↑ Galligan JJ, Wepy JA, Streeter MD, Kingsley PJ, Mitchener MM, Wauchope OR, Beavers WN, Rose KL, Wang T, Spiegel DA, Marnett LJ (September 2018). "Methylglyoxal-derived posttranslational arginine modifications are abundant histone marks". Proc Natl Acad Sci USA. 115 (37): 9228–33. Bibcode:2018PNAS..115.9228G. doi: 10.1073/pnas.1802901115 . PMC   6140490 . PMID   30150385.
  10. ↑ Zheng Q, Omans ND, Leicher R, Osunsade A, Agustinus AS, Finkin-Groner E, D'Ambrosio H, Liu B, Chandarlapaty S, Liu S, David Y (March 2019). "Reversible histone glycation is associated with disease-related changes in chromatin architecture". Nat Commun. 10 (1): 1289. Bibcode:2019NatCo..10.1289Z. doi:10.1038/s41467-019-09192-z. PMC   6426841 . PMID   30894531.
  11. ↑ Oya, Tomoko; Hattori, Nobutaka; Mizuno, Yoshikuni; Miyata, Satoshi; Maeda, Sakan; Osawa, Toshihiko; Uchida, Koji (1999). "Methylglyoxal Modification of Protein". Journal of Biological Chemistry. 274 (26): 18492–502. doi: 10.1074/jbc.274.26.18492 . PMID   10373458.
  12. 1 2 Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science. 2017 Jul 14;357(6347):208-211. doi: 10.1126/science.aag1095. Epub 2017 Jun 8. PMID 28596309
  13. ↑ Rabbani N; Godfrey, L; Xue, M; Shaheen, F; Geoffrion, M; Milne, R; Thornalley, PJ (May 26, 2011). "Glycation of LDL by methylglyoxal increases arterial atherogenicity. A possible contributor to increased risk of cardiovascular disease in diabetes". Diabetes. 60 (7): 1973–80. doi:10.2337/db11-0085. PMC   3121424 . PMID   21617182.
  14. ↑ Spektrum: Diabetische Neuropathie: Methylglyoxal verstärkt den Schmerz: DAZ.online. Deutsche-apotheker-zeitung.de (2012-05-21). Retrieved on 2012-06-11.
  15. ↑ Bierhaus, Angelika; Fleming, Thomas; Stoyanov, Stoyan; Leffler, Andreas; Babes, Alexandru; Neacsu, Cristian; Sauer, Susanne K; Eberhardt, Mirjam; et al. (2012). "Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy". Nature Medicine. 18 (6): 926–33. doi:10.1038/nm.2750. PMID   22581285. S2CID   205389296.
  16. ↑ Israili, ZH (2014). "Antimicrobial properties of honey". American Journal of Therapeutics . 21 (4): 304–23. doi:10.1097/MJT.0b013e318293b09b. PMID   23782759.
  17. ↑ Wallace A, Eady S, Miles M, Martin H, McLachlan A, Rodier M, Willis J, Scott R, Sutherland J (April 2010). "Demonstrating the safety of manuka honey UMF® 20+ in a human clinical trial with healthy individuals". Br J Nutr. 103 (7): 1023–8. doi: 10.1017/S0007114509992777 . PMID   20064284.
  18. ↑ Degen J, Vogel M, Richter D, Hellwig M, Henle T (October 2013). "Metabolic transit of dietary methylglyoxal". J Agric Food Chem. 61 (43): 10253–60. doi:10.1021/jf304946p. PMID   23451712.
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