Methylglyoxal – An emerging biomarker for diabetes mellitus diagnosis and its detection methods

Bhat, Lakshmishri Ramachandra; Vedantham, Srinivasan; Krishnan, Uma Maheswari; Rayappan, John Bosco Balaguru

doi:10.1016/j.bios.2019.03.010

Cited by 66 publications

(45 citation statements)

References 205 publications

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“…Consistently, we show that Sll0067 catalyzes the conjugation of GSH with MG, the first step in MG detoxification by the Glx enzymes. These findings are important because the conjugation of GSH with MG is always described as spontaneous (nonenzymatic) in all organisms ( 2 – 4 ). Our report will likely stimulate research on MG signaling and detoxification in humans and animals (with a possible influence on the identification of biomarkers and drugs), plants (with possible influence on agriculture), and cyanobacteria (with influence on the production of carbon-based chemicals, such as lactate) ( 14 ).…”

Section: Introductionmentioning

confidence: 98%

“…Methylglyoxal (MG) is a very dangerous dicarbonyl compound that strongly interacts with lipids, nucleic acids, and the lysine and arginine residues of proteins, generating advanced glycation end products (AGEs) that strongly disturb cell metabolism in prokaryotes ( 1 ) and eukaryotes ( 2 , 3 ). In fact, MG has a dual nature depending on its concentrations within the cells, acting in signaling at low concentrations while provoking detrimental effects at high concentrations ( 2 , 4 ). In humans, MG is implicated in diabetes and age-related disorders, such as retinopathy, nephropathy, cancer, and Parkinson’s and Alzheimer’s diseases ( 3 ), and MG is increasingly regarded as a marker of diabetes-related diseases.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, various enzymes generate MG from (i) the aminoacetone produced by glycine and threonine metabolisms (monoamine oxidase), (ii) the fatty acid-derived acetone (cytochrome P450), and (iii) the elimination of an inorganic phosphate from DHAP (MG synthase [MGS]) ( 2 , 3 ). MG can be detected directly through derivatization reactions performed under acidic conditions to avoid the spontaneous production of MG from DHAP and G3P ( 2 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Then, HTA is isomerized by glyoxalase I (GlxI; S - d- lactoylglutathione lyase; EC 4.4.1.5) to S - d- lactoylglutathione (S-lactoylGSH) that is hydrolyzed by glyoxalase II (GlxII; S -2-hydroxyacylglutathione hydrolase; EC 3.1.2.6) to release d- lactate and GSH. MG can also be detoxified by the following enzymes: MG dehydrogenase, aldehyde dehydrogenases, aldo-keto reductases, α-dicarbonyl/ l -xylulose reductase, and the MG reductase ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

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Methylglyoxal Detoxification Revisited: Role of Glutathione Transferase in Model Cyanobacterium Synechocystis sp. Strain PCC 6803

Kammerscheit

Hecker

Rouhier

et al. 2020

mBio

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Methylglyoxal (MG) is a detrimental metabolic by-product that threatens most organisms (in humans MG causes diabetes). MG is predominantly detoxified by the glyoxalase pathway. This process begins with the conjugation of MG with glutathione (GSH), yielding a hemithioacetal product that is subsequently transformed by the glyoxalase enzymes into d-lactate and GSH. MG has been overlooked in photosynthetic organisms, although they inevitably produce it not only by the catabolism of sugars, lipids, and amino acids, as do heterotrophic organisms, but also by their active photoautotrophic metabolism. This is especially true for cyanobacteria that are regarded as having developed photosynthesis and GSH-dependent enzymes to detoxify the reactive oxygen species produced by their photosynthesis (CO2 assimilation) and respiration (glucose catabolism), which they perform in the same cell compartment. In this study, we used a combination of in vivo and in vitro approaches to characterize a logical, but as yet never described, link between MG detoxification and a (prokaryotic) representative of the evolutionarily conserved glutathione transferase (GST) detoxification enzymes. We show that the Sll0067 GST of the model cyanobacterium Synechocystis sp. strain PCC 6803 plays a prominent role in MG tolerance and detoxification, unlike the other five GSTs of this organism. Sll0067 catalyzes the conjugation of MG with GSH to initiate its elimination driven by glyoxalases. These results are novel because the conjugation of MG with GSH is always described as nonenzymatic. They will certainly stimulate the analysis of Sll0067 orthologs from other organisms with possible impacts on human health (development of biomarkers or drugs) and/or agriculture. IMPORTANCE In most organisms, methylglyoxal (MG), a toxic metabolite by-product that causes diabetes in humans, is predominantly detoxified by the glyoxalase enzymes. This process begins with the so-called “spontaneous” conjugation of MG with the cytoprotectant metabolite glutathione (GSH). In this study, we unravel a logical, but as yet unsuspected, link between MG detoxification and a (prokaryotic) representative of the ubiquitous glutathione transferase (GST) enzymes. We show that a GST of a model cyanobacterium plays a prominent role in the detoxification of MG in catalyzing its conjugation with GSH. This finding is important because this reaction, always regarded as nonenzymatic, could exist in plants and/or human and thus have an impact on agriculture and/or human health.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Methylglyoxal Detoxification Revisited: Role of Glutathione Transferase in Model Cyanobacterium Synechocystis sp. Strain PCC 6803

Kammerscheit

Hecker

Rouhier

et al. 2020

mBio

View full text Add to dashboard Cite

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“…DM is characterized by abnormal glucose metabolism caused by the relative or absolute deficiency of insulin . DM is mainly divided into type 1 (T1DM), type 2 (T2DM) and gestational diabetes (GDM).…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0028502 and hsa_circ_0076251 are potential novel biomarkers for hepatocellular carcinoma

et al. 2019

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Circular RNAs (circRNAs) have been increasingly revealed to be desirable biomarkers for some tumors, including hepatocellular carcinoma (HCC). Combined with our previous microarray screening results, we aimed to determine the hsa_circ_0028502 and hsa_circ_0076251 expression features in HCC, analyze the relationship between their expression level and clinical and pathological characteristics, and investigate their diagnostic and prognostic values. Our data demonstrated that the hsa_circ_0028502 and hsa_circ_0076251 levels were considerably lower in HCC tissues than in adjacent paracancerous tissues (P < .001). Further study revealed that hsa_circ_0028502 expression levels were related to tumor node metastasis (TNM) stage (P = .015) and that hsa_circ_0076251 expression levels were related to Barcelona Clinic Liver Cancer (BCLC) stage (P = .038), comorbidity with type 2 diabetes mellitus (P = .023) and the presence of serum HbsAg (P = .044). Furthermore, the degree of expression of both hsa_circ_0028502 and hsa_circ_0076251 increased from HCC to liver cirrhosis (LC) to chronic hepatitis (CH). The receiver operating characteristic (ROC) curve demonstrated that hsa_circ_0028502 and hsa_circ_0076251 could serve as fairly accurate markers to distinguish HCC tissues from CH tissues and LC tissues, as well as distinguishing LC tissues from CH tissues. Cox regression analysis showed that low expression of has_circ_0076251 was associated with unfavorable survival rates in HCC (HR = 0.46; 95% CI = 0.22‐0.98; P < .05). These findings implied that hsa_circ_0028502 and hsa_circ_0076251 were potentially valuable biomarkers for HCC diagnosis, whereas hsa_circ_0076251 could be used as a prognostic indicator for HCC.

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Highly sensitive spectrofluorimetric method for the determination of the genotoxic methylglyoxal in glycerol‐containing pharmaceuticals and dietary supplements

et al. 2022

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Methylglyoxal (MGO) is a genotoxic α-dicarbonyl compound. Recently, it was found to be formed in glycerol preparations during storage through auto-oxidation. A simple fluorimetric determination of the carcinogenic degradation product of glycerol, MGO, was developed and validated. The proposed method is based on the derivatization of MGO with 4-carbomethoxybenzaldehyde (CMBA) and ammonium acetate to yield a fluorescent imidazole derivative that can be measured at 415 nm after excitation at 322 nm. The optimized conditions were determined to be 0.2 M CMBA, 1.0 M ammonium acetate and a reaction time of 40 min at 90 C using ethanol as diluting solvent. The linear range was 10.0-200.0 ng/ml. Detection and quantification limits were 2.22 and 6.72 ng/ml, respectively. The proposed method was validated according to International Council for Harmonisation (ICH) guidelines and compared with the reported method and no significant difference was found. It was successfully applied for the determination of MGO in six different glycerol-containing pharmaceutical preparations and dietary supplements.

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Methylglyoxal – An emerging biomarker for diabetes mellitus diagnosis and its detection methods

Cited by 66 publications

References 205 publications

Methylglyoxal Detoxification Revisited: Role of Glutathione Transferase in Model Cyanobacterium Synechocystis sp. Strain PCC 6803

Methylglyoxal Detoxification Revisited: Role of Glutathione Transferase in Model Cyanobacterium Synechocystis sp. Strain PCC 6803

Hsa_circ_0028502 and hsa_circ_0076251 are potential novel biomarkers for hepatocellular carcinoma

Highly sensitive spectrofluorimetric method for the determination of the genotoxic methylglyoxal in glycerol‐containing pharmaceuticals and dietary supplements

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