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Showing papers on "Methylglyoxal published in 2008"


Journal ArticleDOI
TL;DR: In this paper, a detailed simulation of glyoxal and methylglyoxal in the GEOS-Chem global 3-D chemical transport model including the best knowledge of source and sink processes was conducted.
Abstract: [1] We construct global budgets of atmospheric glyoxal and methylglyoxal with the goal of quantifying their potential for global secondary organic aerosol (SOA) formation via irreversible uptake by aqueous aerosols and clouds. We conduct a detailed simulation of glyoxal and methylglyoxal in the GEOS-Chem global 3-D chemical transport model including our best knowledge of source and sink processes. Our resulting best estimates of the global sources of glyoxal and methylglyoxal are 45 Tg a−1 and 140 Tg a−1, respectively. Oxidation of biogenic isoprene contributes globally 47% of glyoxal and 79% of methylglyoxal. The second most important precursors are acetylene (mostly anthropogenic) for glyoxal and acetone (mostly biogenic) for methylglyoxal. Both acetylene and acetone have long lifetimes and provide a source of dicarbonyls in the free troposphere. Atmospheric lifetimes of glyoxal and methylglyoxal in the model are 2.9 h and 1.6 h, respectively, mostly determined by photolysis. Simulated dicarbonyl concentrations in continental surface air at northern midlatitudes are in the range 10–100 ppt, consistent with in situ measurements. On a global scale, the highest concentrations are over biomass burning regions, in agreement with glyoxal column observations from the SCIAMACHY satellite instrument. SCIAMACHY and a few ship cruises also suggest a large marine source of dicarbonyls missing from our model. The global source of SOA from the irreversible uptake of dicarbonyls in GEOS-Chem is 11 Tg C a−1, including 2.6 Tg C a−1 from glyoxal and 8 Tg C a−1 from methylglyoxal; 90% of this source takes place in clouds. The magnitude of the global SOA source from dicarbonyls is comparable to that computed in GEOS-Chem from the standard mechanism involving reversible partitioning of semivolatile products from the oxidation of monoterpenes, sesquiterpenes, isoprene, and aromatics.

578 citations


Journal ArticleDOI
TL;DR: It is appreciated that glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome and represents part of the enzymatic defence against glycation.
Abstract: Glycation of proteins, nucleotides and basic phospholipids by glyoxal and methylglyoxal--physiological substrates of glyoxalase 1--is potentially damaging to the proteome, genome and lipidome. Glyoxalase 1 suppresses glycation by these alpha-oxoaldehyde metabolites and thereby represents part of the enzymatic defence against glycation. Albert Szent-Gyorgyi pioneered and struggled to understand the physiological function of methylglyoxal and the glyoxalase system. We now appreciate that glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome. Latest research suggests there are functional modifications of this process--implying a role in cell signalling, ageing and disease.

417 citations


Journal ArticleDOI
TL;DR: In this paper, aqueous phase photo-oxidation experiments of methylglyoxal and hydroxyl radical were conducted to simulate cloud processing. But little is known about the composition of secondary organic aerosol (SOA) formed through cloud processing, which may simplify the incorporation of oligomers into atmospheric SOA models.

309 citations


Journal ArticleDOI
TL;DR: Using HPLC a fraction of New Zealand manuka honey has been isolated, which gives rise to the non-peroxide antibacterial activity, and this fraction proved to be methylglyoxal, a highly reactive precursor in the formation of advanced glycation endproducts (AGEs).

280 citations


Journal ArticleDOI
TL;DR: Both proline and glycinebetaine are suggested to provide a protective action against NaCl-induced oxidative damage by reducing protein carbonylation, and enhancing antioxidant defense and MG detoxification systems.

267 citations


Journal ArticleDOI
TL;DR: This is the first report that proanthocyanidins can effectively scavenge reactive carbonyl species and thus inhibit the formation of AGEs, which show great potential to be developed as agents to alleviate diabetic complications.
Abstract: Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. In this study, the inhibitory effect of cinnamon bark on the formation of advanced glycation endproducts (AGEs) was investigated in a bovine serum albumin (BSA)-glucose model. Several phenolic compounds, such as catechin, epicatechin, and procyanidin B2, and phenol polymers were identified from the subfractions of aqueous cinnamon extract. These compounds showed significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal (MGO), an intermediate reactive carbonyl of AGE formation. Preliminary study on the reaction between MGO and procyanidin B2 revealed that MGO-procyanidin B2 adducts are primary products which are supposed to be stereoisomers. This is the first report that proanthocyanidins can effectively scavenge reactive carbonyl species and thus inhibit the formation of AGEs. As proanthocyanidins behave in a similar fashion as aminoguanidine (AG), the first AGE inhibitor explored in clinical trials, they show great potential to be developed as agents to alleviate diabetic complications.

224 citations


Journal ArticleDOI
TL;DR: Reactive oxygen species-induced modification of HIF1α by the glyoxalase 1 (GLO1) substrate methylglyoxal is hypothesized to cause impaired ischemia-induced vasculogenesis in patients with diabetes.

223 citations


Journal ArticleDOI
01 Aug 2008-Diabetes
TL;DR: It is concluded that activation of nrf2 may prevent biochemical dysfunction and related functional responses of endothelial cells induced by hyperglycemia in which increased expression of transketolase has a pivotal role.
Abstract: OBJECTIVE—Sulforaphane is an activator of transcription factor NF-E2–related factor-2 (nrf2) that regulates gene expression through the promoter antioxidant response element (ARE). Nrf2 regulates the transcription of a battery of protective and metabolic enzymes. The aim of this study was to assess whether activation of nrf2 by sulforaphane in human microvascular endothelial cells prevents metabolic dysfunction in hyperglycemia. RESEARCH DESIGN AND METHODS—Human microvascular HMEC-1 endothelial cells were incubated in low and high glucose concentrations (5 and 30 mmol/l, respectively), and activation of nrf2 was assessed by nuclear translocation. The effects of sulforaphane on multiple pathways of biochemical dysfunction, increased reactive oxygen species (ROS) formation, hexosamine pathway, protein kinase C (PKC) pathway, and increased formation of methylglyoxal were assessed. RESULTS—Activation of nrf2 by sulforaphane induced nuclear translocation of nrf2 and increased ARE-linked gene expression, for example, three- to fivefold increased expression of transketolase and glutathione reductase. Hyperglycemia increased the formation of ROS—an effect linked to mitochondrial dysfunction and prevented by sulforaphane. ROS formation was increased further by knockdown of nrf2 and transketolase expression. This also abolished the counteracting effect of sulforaphane, suggesting mediation by nrf2 and related increase of transketolase expression. Sulforaphane also prevented hyperglycemia-induced activation of the hexosamine and PKC pathways and prevented increased cellular accumulation and excretion of the glycating agent methylglyoxal. CONCLUSIONS—We conclude that activation of nrf2 may prevent biochemical dysfunction and related functional responses of endothelial cells induced by hyperglycemia in which increased expression of transketolase has a pivotal role.

223 citations


Journal ArticleDOI
TL;DR: It is arrived at that a tight junction exists between methylglyoxal toxicity and free radical (particularly ROS) generation, though the toxicity of 1,2-dicarbonyl evolves even under anaerobic conditions, too.

220 citations


Journal ArticleDOI
TL;DR: In this paper, the anti-glycation activity of four kinds of beans including mung beans, black beans, soybeans and cowpea was evaluated in a bovine serum albumin (BSA)-glucose model and the inhibitory activities of extracts of the four beans were found to be highly correlated with their total phenolic contents.

211 citations


Journal ArticleDOI
TL;DR: The role of glyoxalase overexpression in conferring salinity tolerance in transgenic tobacco is shown to be viable and the feasibility of same in a crop like rice through overproduction of gly oxalase II is demonstrated.
Abstract: Earlier we have shown the role of glyoxalase overexpression in conferring salinity tolerance in transgenic tobacco. We now demonstrate the feasibility of same in a crop like rice through overproduction of glyoxalase II. The rice glyoxalase II was cloned in pCAMBIA1304 and transformed into rice (Oryza sativa cv PB1) via Agrobacterium. The transgenic plants showed higher constitutive activity of glyoxalase II that increased further upon salt stress, reflecting the upregulation of endogenous glyoxalase II. The transgenic rice showed higher tolerance to toxic concentrations of methylglyoxal (MG) and NaCl. Compared with non-transgenics, transgenic plants at the T1 generation exhibited sustained growth and more favorable ion balance under salt stress conditions.

Journal ArticleDOI
TL;DR: In this article, it was shown that dicarbonyl glycation damage to the mitochondrial proteome may be a preceding event to mitochondrial dysfunction leading to oxidative stress, leading to increased formation of reactive oxygen species and oxidative and nitrosative damage.
Abstract: Protection of mitochondrial proteins from glycation by endogenous dicarbonyl compounds, methylglyoxal and glyoxal, was found recently to prevent increased formation of reactive oxygen species and oxidative and nitrosative damage to the proteome during aging and produce life extension in the nematode Caenorhabditis elegans This suggests that dicarbonyl glycation damage to the mitochondrial proteome may be a preceding event to mitochondrial dysfunction leading to oxidative stress Future research will address the functional charges in mitochondrial proteins that are the targets for dicarbonyl glycation

Journal ArticleDOI
TL;DR: The mechanism of detoxification of glyoxal and methylglyoxal by the Glyoxalase system is described and also the possibility to eliminate glycated proteins by deglycation enzymes is described.
Abstract: Advanced glycation end-products (AGEs) are formed from the so-called Amadori products by rearrangement followed by other reactions giving rise to compounds bound irreversibly. The structure of some of them is shown and the mechanism of formation is described. Several AGE binding molecules (Receptors for AGE, RAGE) are known and it is thought that many of the effects caused by AGEs are mediated by RAGE. Some of these were shown to be toxic, and called TAGE. The mechanism of detoxification of glyoxal and methylglyoxal by the glyoxalase system is described and also the possibility to eliminate glycated proteins by deglycation enzymes. Compounds able to inhibit AGEs formation are also taken into consideration.

Journal ArticleDOI
23 Oct 2008-PLOS ONE
TL;DR: Results indicate that inhibition of Glo1 by curcumin may result in non-tolerable levels of MGO and GSH, which, in turn, modulate various metabolic cellular pathways including depletion of cellular ATP and G SH content.
Abstract: Background Glyoxalases (Glo1 and Glo2) are involved in the glycolytic pathway by detoxifying the reactive methylglyoxal (MGO) into D-lactate in a two-step reaction using glutathione (GSH) as cofactor. Inhibitors of glyoxalases are considered as anti-inflammatory and anti-carcinogenic agents. The recent finding that various polyphenols modulate Glo1 activity has prompted us to assess curcumin's potency as an Glo1 inhibitor. Methodology/principal findings Cultures of whole blood cells and tumor cell lines (PC-3, JIM-1, MDA-MD 231 and 1321N1) were set up to investigate the effect of selected polyphenols, including curcumin, on the LPS-induced cytokine production (cytometric bead-based array), cell proliferation (WST-1 assay), cytosolic Glo1 and Glo2 enzymatic activity, apoptosis/necrosis (annexin V-FITC/propidium iodide staining; flow cytometric analysis) as well as GSH and ATP content. Results of enzyme kinetics revealed that curcumin, compared to the polyphenols quercetin, myricetin, kaempferol, luteolin and rutin, elicited a stronger competitive inhibitory effect on Glo1 (K(i) = 5.1+/-1.4 microM). Applying a whole blood assay, IC(50) values of pro-inflammatory cytokine release (TNF-alpha, IL-6, IL-8, IL-1beta) were found to be positively correlated with the K(i)-values of the aforementioned polyphenols. Moreover, whereas curcumin was found to hamper the growth of breast cancer (JIMT-1, MDA-MB-231), prostate cancer PC-3 and brain astrocytoma 1321N1 cells, no effect on growth or vitality of human primary hepatocytes was elucidated. Curcumin decreased D-lactate release by tumor cells, another clue for inhibition of intracellular Glo1. Conclusions/significance The results described herein provide new insights into curcumin's biological activities as they indicate that inhibition of Glo1 by curcumin may result in non-tolerable levels of MGO and GSH, which, in turn, modulate various metabolic cellular pathways including depletion of cellular ATP and GSH content. This may account for curcumin's potency as an anti-inflammatory and anti-tumor agent. The findings support the use of curcumin as a potential therapeutic agent.

Journal ArticleDOI
TL;DR: It is discovered that methyl-gerfelin (M-GFN), the methyl ester of the natural product gerfelin, suppresses osteoclastogenesis and is associated with many bone-related diseases, such as osteoporosis.
Abstract: Osteoclasts, bone-resorptive multinucleated cells derived from hematopoietic stem cells, are associated with many bone-related diseases, such as osteoporosis. Osteoclast-targeting small-molecule inhibitors are valuable tools for studying osteoclast biology and for developing antiresorptive agents. Here, we have discovered that methyl-gerfelin (M-GFN), the methyl ester of the natural product gerfelin, suppresses osteoclastogenesis. By using M-GFN-immobilized beads, glyoxalase I (GLO1) was identified as an M-GFN-binding protein. GLO1 knockdown and treatment with an established GLO1 inhibitor in osteoclast progenitor cells interfered with osteoclast generation, suggesting that GLO1 activity is required for osteoclastogenesis. In cells, GLO1 plays a critical role in the detoxification of 2-oxoaldehydes, such as methylglyoxal. M-GFN inhibited the enzymatic activity of GLO1 in vitro and in situ. Furthermore, the cocrystal structure of the GLO1/M-GFN complex revealed the binding mode of M-GFN at the active site of GLO1. These results suggest that M-GFN targets GLO1, resulting in the inhibition of osteoclastogenesis.

Journal ArticleDOI
TL;DR: Overexpression of the glyoxalase pathway in transgenic tobacco and rice plants has been found to check an increase of ROS and MG under stress conditions by maintaining glutathione homeostasis and antioxidant enzyme levels.
Abstract: Methylglyoxal (MG) is a highly reactive cytotoxic alpha-oxoaldehyde compound and is formed endogenously via different enzymatic and non-enzymatic reactions. In plants MG is detoxified mainly via the glyoxalase system that is comprised of two enzymes, glyoxalase I and glyoxalase II. Glyoxalase I converts MG to S-D-lactoylglutathione by utilizing glutathione, while glyoxalase II converts S-D-lactoylglutathione to D-lactic acid, and during this reaction glutathione is regenerated. The presence and characterization of both glyoxalase I and II has been reported in many plants and the genes encoding these have been cloned and found to be regulated under various environmental conditions. In plants, MG has been found to be present during normal growth conditions and it accumulates to higher levels under various environmental stresses. Abiotic and heavy metal stresses induce reactive oxygen species (ROS) and MG. Overexpression of the glyoxalase pathway in transgenic tobacco and rice plants has been found to check an increase of ROS and MG under stress conditions by maintaining glutathione homeostasis and antioxidant enzyme levels. There is also evidence that in addition to glyoxalase, other pathways, such as the aldose reductase pathway, may also be involved in MG detoxification in plants. To unravel the role of MG and the glyoxalase pathway in signal transduction during environmental stress conditions in plants is a topic of future research interest. In this paper we review work on plant glyoxalases especially with respect to their role under abiotic stresses.

Journal ArticleDOI
TL;DR: Upregulation of P5CS in aromatic rice Tainung 72 may contribute to the increase of Delta(1)-pyrroline-5-carboxylic acid level and thus leads to the accumulation of an extra amount of 2-acetyl-1-pyr roline.
Abstract: 2-Acetyl-1-pyrroline (2-AP) was identified as the major flavor compound in aromatic rice varieties Tainung 71 and 72. In order to understand the mechanism of 2-AP biosynthesis in aromatic rice, we studied the formation of putative precursors, Δ1-pyrroline-5-carboxylic acid and methylglyoxal. The endogenous Δ1-pyrroline-5-carboxylic acid contents of Tainung 71 and 72 calli reached 191 to 276%, compared to nonaromatic rice Tainung 67. In addition, calli of Tainung 71 and 72 contained 1.30- and 1.36-fold, respectively, higher methylglyoxal levels than that of Tainung 67. Specific enzyme activities of Δ1-pyrroline-5-carboxylic acid-synthetic enzyme including Δ1-pyrolline-5-carboxylic acid synthetase (P5CS) and ornithine aminotransferase (OAT) increased significantly in aromatic rice varieties. The expression levels of P5CS1 and P5CS2 genes were found to be significantly higher in aromatic rice than nonaromatic rice. Results of a tracer experiment with 15N-labeled glutamic acid revealed that the nitrogen atom ...

Journal ArticleDOI
TL;DR: The sensitive and specific determination of advanced glycation end products (AGEs) is of considerable interest because these compounds have been associated with pro‐oxidative and proinflammatory effects in vivo.
Abstract: The sensitive and specific determination of advanced glycation end products (AGEs) is of considerable interest because these compounds have been associated with pro-oxidative and proinflammatory effects in vivo. AGEs form when carbonyl compounds, such as glucose and its oxidation products, glyoxal and methylglyoxal, react with the epsilon-amino group of lysine and the guanidino group of arginine to give structures including N epsilon-(carboxymethyl)lysine (CML), N epsilon-(carboxyethyl)lysine, and hydroimidazolones. CML is frequently used as a marker for AGEs in general. It exists in both the free or peptide-bound forms. Analysis of CML involves its extraction from the food (including protein hydrolysis to release any peptide-bound adduct) and determination by immunochemical or instrumental means. Various factors must be considered at each step of the analysis. Extraction, hydrolysis, and sample clean-up are all less straight forward for food samples, compared to plasma and tissue. The immunochemical and instrumental methods all have their advantages and disadvantages, and no perfect method exists. Currently, different procedures are being used in different laboratories, and there is an urgent need to compare, improve, and validate methods.

Journal ArticleDOI
TL;DR: The findings suggest that methylglyoxal-induced neurotoxicity occurs through the impairment of detoxification pathway and depletion of reduced glutathione, which triggers widespread apoptotic cell death, occurring through the convergence of both mitochondrial and Fas-receptor pathways.

Journal ArticleDOI
TL;DR: This review attempts to integrate DM-associated literature related to methylglyoxal, which has effects on insulin secretion from pancreatic beta-cells and is a major precursor of advanced glycation endproducts (AGE).
Abstract: A large literature has developed around methylglyoxal (MG) concerning its role in diabetes mellitus (DM) and in the development of diabetic complications. This is related to the observation that levels of reactive aldehydes, especially 2-oxoaldehydes such as MG, are elevated in DM. There are numerous metabolic origins of MG that are accentuated in DM. MG has effects on insulin secretion from pancreatic beta-cells and is a major precursor of advanced glycation endproducts (AGE). Consequently, MG has a role in primary DM as well in the etiology of long-term complications. There is an extensive literature concerning the enzymes involved in the metabolism of MG, especially the glyoxalase system and aldose reductase. In addition, there is a rapidly developing literature on the direct and indirect effects of MG on signaling pathways that impact DM. This review attempts to integrate this DM-associated literature related to MG.

Journal ArticleDOI
TL;DR: Results indicated that MGO mediates JNK- and p38-dependent EC inflammatory responses, which might be independent of oxidative stress, and MGO-induced morphological cell damage seems unlikely to be associated with COX-2-PGE(2).
Abstract: Methylglyoxal (MGO) is a reactive metabolite of glucose. Since the plasma concentration of MGO is increased in diabetic patients, MGO is implicated in diabetes-associated vascular endothelial cells...

Journal ArticleDOI
TL;DR: The results demonstrated that activation of mitogen-activated protein kinase signal pathways (JNK and p38) participated in the methylglyoxal-induced Neuro-2A cell apoptosis process, suggesting that phenolic acids possess cytoprotective ability in the prevention of diabetic neuropathy complication.
Abstract: In the process of glycation, methylglyoxal is a reactive dicarbonyl compound physiologically generated as an intermediate of glycolysis, and is found in high levels in blood or tissue of diabetic models. Biological glycation has been commonly implicated in the development of diabetic microvascular complications of neuropathy. Increasing evidence suggests that neuronal cell cycle regulatory failure followed by apoptosis is an important mechanism in the development of diabetic neuropathy complication. Naturally occurring antioxidants, especially phenolic acids have been recommended as the major bioactive compounds to prevent chronic diseases and promote health benefits. The objective of this study was to investigate the inhibitory abilities of phenolic acids (chlorogenic acid, syringic acid and vanillic acid) on methylglyoxal-induced mouse Neuro-2A neuroblastoma (Neuro-2A) cell apoptosis in the progression of diabetic neuropathy. The data indicated that methylglyoxal induced mouse Neuro-2A neuroblastoma (Neuro-2A) cell apoptosis via alternation of mitochondria membrane potential and Bax/Bcl-2 ratio, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase. Furthermore, the results demonstrated that activation of mitogen-activated protein kinase signal pathways (JNK and p38) participated in the methylglyoxal-induced Neuro-2A cell apoptosis process. Treatment of Neuro-2A cells with phenolic acids markedly suppresses cell apoptosis induced by methylglyoxal, suggesting that phenolic acids possess cytoprotective ability in the prevention of diabetic neuropathy complication.

Journal ArticleDOI
TL;DR: Increased methylglyoxal, AGEs, oxidative stress and reduced eNOS along with structural remodeling of the vessel wall in the aorta and mesenteric artery likely play a role in the pathogenesis of hypertension.
Abstract: ObjectivesMethylglyoxal is a reactive dicarbonyl intermediate of metabolism produced in the body. It reacts with certain proteins and forms damaging advanced glycation endproducts (AGEs) such as Ne-carboxyethyl-lysine (CEL) and Ne-carboxymethyl-lysine (CML). Increased methylglyoxal levels are found

Journal ArticleDOI
TL;DR: In conclusion, aminoacetone is the most potent precursor of MG production in VSMCs, followed by fructose and d-glucose, which could have important implications in relation to high dietary fructose and protein intake.
Abstract: Methylglyoxal (MG), a metabolic by-product, reacts with certain proteins to yield irreversible advanced glycation end products (AGEs) and increases oxidative stress that causes the pathophysiological changes in diabetes, hypertension, and aging. Although MG production from glucose has been well documented, the contribution of other intermediates of different metabolic pathways to MG formation is far less known. Our aim was to determine and compare the formation of MG, MG-induced AGE, N(epsilon)-carboxyethyl-lysine (CEL), inducible nitric oxide synthase (iNOS), nitric oxide, and peroxynitrite from different metabolic precursors in cultured rat aortic vascular smooth muscle cells (VSMCs). High-performance liquid chromatography was used to determine MG levels, whereas nitrite + nitrate, indicators of nitric oxide production, and peroxynitrite levels were measured with specific assay kits. The CEL and iNOS were detected using immunocytochemistry. There was a concentration-dependent increase in MG levels in VSMCs after 3-hour incubation with 5, 15, and 25 mmol/L of D-glucose, fructose, or aminoacetone. Aminoacetone produced a 7-fold increase in MG levels above the basal value followed by fructose (3.9-fold), D-glucose (3.5-fold), acetol (2.8-fold), and sucrose (2.3-fold) after a 3-hour incubation with 25 mmol/L of each precursor. L-Glucose, 3-O-methylglucose, and mannitol had no effect on MG production. All precursors, except l-glucose, 3-O-methylglucose and mannitol, increased CEL. Aminoacetone, D-glucose, and fructose significantly increased iNOS, nitrite/nitrate, and peroxynitrite levels. In conclusion, aminoacetone is the most potent precursor of MG production in VSMCs, followed by fructose and d-glucose. This could have important implications in relation to high dietary fructose and protein intake.

Journal ArticleDOI
TL;DR: An overview of the changing role of methylglyoxal from a historical aspect is given and it is arrived at that methyl glyoxal is tightly bound to glycolysis from an evolutionary perspective, its production therefore being inevitable.
Abstract: Methylglyoxal, an alpha-oxoaldehyde discovered in the 1880s, has had a hectic scientific career, at times being considered of fundamental importance and at other times viewed as playing a very subordinate role. Much has been learned about methylglyoxal, but the function of its production in the metabolic machinery is still unknown. This paper gives an overview of the changing role of methylglyoxal from a historical aspect and arrives at the conclusion that methylglyoxal is tightly bound to glycolysis from an evolutionary perspective, its production therefore being inevitable. It is not situated in the main stream of the glycolytic sequence, but a role can be assigned to its production in the phosphate supply of operating glycolysis in some prokaryotes and yeast under conditions of phosphate deficiency. This function is presumed to be performed by the enzyme methylglyoxal synthase, which is specialized for the conversion of dihydroxyacetone-phosphate to methylglyoxal. However, it is still unknown whether this enzyme and this kind of regulation also exist in animals.

Journal ArticleDOI
TL;DR: The correlation of elevated MG and various reactive oxygen species, and the enzymes that produce them or take part in their disposal, such as antioxidant enzymes and cofactors are summarized.
Abstract: Methylglyoxal (MG) is a reactive dicarbonyl intermediate of the glycolytic pathway. Increased oxidative stress is associated with conditions of increased MG, such as diabetes mellitus. Increased oxidative stress is due to an increase in highly reactive by-products of metabolic pathways, the so-called reactive oxygen species, such as superoxide anion, hydroxyl radical, hydrogen peroxide, nitric oxide and peroxynitrite. These reactive species react with a variety of proteins, enzymes, lipids, DNA and other molecules and disrupt their normal function. Oxidative stress causes many pathological changes that lead to vascular complications of diabetes mellitus, hypertension, neurodegenerative diseases and aging. In this review we summarize the correlation of elevated MG and various reactive oxygen species, and the enzymes that produce them or take part in their disposal, such as antioxidant enzymes and cofactors. The findings reported in various studies reviewed have started filling in gaps in our knowledge that will ultimately provide us with a clear picture of how the whole process that causes cellular dysfunction is initiated.

Journal ArticleDOI
TL;DR: Although extents of modification are usually low, the dicarbonyl proteome is a critical feature of the impact of glycation on physiological function—particularly in mitochondrial dysfunction, vascular disease, and potentially in disorders of lipoprotein metabolism.
Abstract: Reactive, physiological, dicarbonyl, glycating agents, glyoxal and methylglyoxal, are arginine-directed glycating agents forming mainly hydroimidazolone residues. Arginine residues have high-frequency occurrence in sites of protein-protein, enzyme substrate and protein-nucleotide binding sites. There is emerging evidence that functionally important arginine residues in proteins are often activated toward dicarbonyl glycation-leading to functional impairment. When uncontrolled, this is associated with aging, degenerative diseases, and metabolic disorders where dicarbonyl glycation may be viewed as damage to the proteome. The glyoxalase system, particularly glyoxalase 1, is the vanguard against dicarbonyl glycation in physiological systems. Functional regulation of glyoxalase I suggests a role for dicarbonyl glycation in cell signaling. Although extents of modification are usually low, the dicarbonyl proteome is a critical feature of the impact of glycation on physiological function-particularly in mitochondrial dysfunction, vascular disease, and potentially in disorders of lipoprotein metabolism.

Journal ArticleDOI
TL;DR: The glyoxalase system catalyzes the conversion of 2-oxoaldehydes into the corresponding 2-hydroxyacids and zinc plays an essential role in their diverse catalytic mechanisms.
Abstract: The glyoxalase system catalyzes the conversion of 2-oxoaldehydes into the corresponding 2-hydroxyacids. This biotransformation involves two separate enzymes, glyoxalase I and glyoxalase II, which bring about two consecutive reactions involving the thiol-containing tripeptide glutathione as a cofactor. The physiologically most important substrate methylglyoxal is converted by glyoxalase I into S-D-lactoyl-glutathione in the first reaction. Subsequently, glyoxalase II catalyzes the hydrolysis of this thiolester into D-lactic acid and free glutathione. The structures of both enzymes have been obtained via molecular cloning, heterologous expression, and X-ray diffraction analysis. Glyoxalase I and glyoxalase II are metalloenzymes and zinc plays an essential role in their diverse catalytic mechanisms. Both enzymes appear linked to a variety of pathological conditions, but further investigations are required to clarify the different physiological aspects of the glyoxalase system.

Journal ArticleDOI
TL;DR: The effort in searching for non‐ or less‐toxic trapping agents of reactive dicarbonyl species from dietary sources is described and it is discovered that commercial beverages contain extremely high levels of MG.
Abstract: Nonenzymic glycation, also known as the Maillard reaction, is a complex series of reactions between reducing sugars and amino compounds. Previous studies have demonstrated that reactive dicarbonyl compounds (e.g., methylglyoxal [MG] and glyoxal [GO]), formed as intermediate products of the Maillard reaction, irreversibly and progressively modify proteins over time and yield advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its complications. Several studies have shown that higher levels of MG are present in diabetic patients' plasma than in healthy people's plasma. Thus, decreasing the levels of MG and GO will be an effective approach to reduce the formation of AGEs and the development of diabetic complications. Here, we briefly describe our effort in searching for non- or less-toxic trapping agents of reactive dicarbonyl species from dietary sources. In addition, we have discovered that commercial beverages contain extremely high levels of MG. The potential hazardous effects of dietary MG on humans remain to be explored.

Journal ArticleDOI
Krishna P. Subedi1, Insook Kim1, Junho Kim1, Bumchan Min, Chankyu Park1 
TL;DR: This study proposes that the primary role of gldA is to remove toxic dihydroxyacetone by converting it into glycerol, which is consistent with NMR data with crude extracts, and is far more efficient than the reverse reaction.
Abstract: The metabolic pathway involving dihydroxyacetone is poorly characterized although novel enzymes associated with this metabolite have recently been demonstrated. The role of GldA in dihydroxyacetone and methylglyoxal metabolism was investigated by purifying the enzyme and characterizing its catalytic ability using nuclear magnetic resonance (NMR) spectroscopy. At neutral pH, the enzyme exhibits much higher affinities towards dihydroxyacetone, methylglyoxal, and glycolaldehyde than glycerol with Km values of 0.30, 0.50, 0.85, and 56 mM, respectively. This is consistent with NMR data with crude extracts, showing that the conversion from dihydroxyacetone to glycerol by GldA is far more efficient than the reverse reaction. Dihydroxyacetone was found to be lethal at higher concentration with an LC50 value of 28 mM compared with 0.4 mM of methylglyoxal, while lactaldehyde was found to exhibit significant growth inhibition in Escherichia coli cells. The toxicity of dihydroxyacetone appears to be due to its intracellular conversion to an aldehyde compound, presumably methylglyoxal, since the glyoxalase mutant becomes sensitive to dihydroxyacetone. Based on information that gldA is preceded in an operon by the ptsA homolog and talC gene encoding fructose 6-phosphate aldolase, this study proposes that the primary role of gldA is to remove toxic dihydroxyacetone by converting it into glycerol.