Protein Modification by Methylglyoxal: Chemical Nature and Synthetic Mechanism of a Major Fluorescent Adduct

Shipanova, I.; Glomb, Marcus A.; Nagaraj, Ramanakoppa H.

doi:10.1006/abbi.1997.0195

Cited by 257 publications

(200 citation statements)

References 53 publications

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“…It is produced as a nonenzymatic by-product of glycolysis (29) and lipid peroxidation (30) and also enzymatically either through stress-induced production from triose phosphates (31) or from dihydroxyacetone phosphate in a reaction catalyzed by MG synthase in bacteria (32). The mechanism(s) of MG production in plants is not yet understood; it is significant, however, that ascorbic acid is a potential precursor of MG (33). We have shown that glycation (protein modification by degraded products of sugars) occurs in the presence of 10 mM ascorbic acid (34), and the concentration of ascorbic acid in chloroplasts is estimated to be 12-25 mM (35).…”

Section: Aor Adr and Akr Cooperatively Scavenge Reactive Carbonyls mentioning

confidence: 94%

NADPH-dependent Reductases Involved in the Detoxification of Reactive Carbonyls in Plants

Yamauchi¹,

Hasegawa²,

Taninaka

et al. 2011

Journal of Biological Chemistry

152

117

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Reactive carbonyls, especially ␣,␤-unsaturated carbonyls produced through lipid peroxidation, damage biomolecules such as proteins and nucleotides; elimination of these carbonyls is therefore essential for maintaining cellular homeostasis. In this study, we focused on an NADPH-dependent detoxification of reactive carbonyls in plants and explored the enzyme system involved in this detoxification process. Using acrolein (CH 2 ‫؍‬ CHCHO) as a model ␣,␤-unsaturated carbonyl, we purified a predominant NADPH-dependent acrolein-reducing enzyme from cucumber leaves, and we identified the enzyme as an alkenal/one oxidoreductase (AOR) catalyzing reduction of an ␣,␤-unsaturated bond. Cloning of cDNA encoding AORs revealed that cucumber contains two distinct AORs, chloroplastic AOR and cytosolic AOR. Homologs of cucumber AORs were found among various plant species, including Arabidopsis, and we confirmed that a homolog of Arabidopsis (At1g23740) also had AOR activity. Phylogenetic analysis showed that these AORs belong to a novel class of AORs. They preferentially reduced ␣,␤-unsaturated ketones rather than ␣,␤-unsaturated aldehydes. Furthermore, we selected candidates of other classes of enzymes involved in NADPH-dependent reduction of carbonyls based on the bioinformatic information, and we found that an aldo-keto reductase (At2g37770) and aldehyde reductases (At1g54870 and At3g04000) were implicated in the reduction of an aldehyde group of saturated aldehydes and methylglyoxal as well as ␣,␤-unsaturated aldehydes in chloroplasts. These results suggest that different classes of NADPH-dependent reductases cooperatively contribute to the detoxification of reactive carbonyls.When plants are subjected to abiotic and/or biotic stresses, oxidative stress often results; this leads to the production of reactive oxygen species, which damage biomolecules such as proteins and lipids. More than half of the fatty acids found in the membranes of chloroplasts and mitochondria, two of the most highly oxidative organelles, are linoleic and linolenic acid. Because linoleic and linolenic acid are sources of many short chain carbonyls through their peroxidation (1), biomolecules in both types of organelles are challenged by the toxicity of reactive compounds, including ␣,␤-unsaturated carbonyls, which are involved in the pathophysiological effects associated with oxidative stress in cells and tissues (2). In fact, ␣,␤-unsaturated carbonyls from peroxidized polyunsaturated fatty acids cause loss of functions in mitochondria (3); chloroplasts have recently been shown to be a major production center of reactive aldehydes (4), and photosynthetic functions are highly sensitive to ␣,␤-unsaturated carbonyls (5-7).The high reactivity of ␣,␤-unsaturated carbonyls is due to the ability of their ␣,␤-unsaturated bonds to form Michael adducts with thiol and amino groups in biomolecules; in the case of ␣,␤-unsaturated aldehydes, the aldehyde group also contributes to reactivity through the formation of Schiff base adducts with amino groups. Thus the targe...

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Section: Aor Adr and Akr Cooperatively Scavenge Reactive Carbonyls mentioning

confidence: 94%

NADPH-dependent Reductases Involved in the Detoxification of Reactive Carbonyls in Plants

Yamauchi¹,

Hasegawa²,

Taninaka

et al. 2011

Journal of Biological Chemistry

152

117

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“…In fact, Ortwerth et al (33) found that ascorbate-derived AGEs can produce ROS, and human lenses contain relatively large amounts of ascorbate. Oxidation of ascorbate produces highly reactive compounds, including dicarbonyls that can form AGEs (34,35).…”

mentioning

confidence: 99%

Early Glycation Products Produce Pentosidine Cross-links on Native Proteins

Chellan¹,

Nagaraj²

2001

Journal of Biological Chemistry

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Bovine lens ␣-crystallin was immobilized on EAHSepharose gel and glycated using D-ribose. Incubation with 500 and 100 mM D-ribose for 2 and 15 days produced short-term glycated (STGP gel) and long-term glycated proteins (LTGP gel). Both STGP and LTGP gels produced oxygen free radicals. Hydroxyl radical production was twice that in STGP gel compared with the LTGP gel. Incubation with the glycated gels produced pentosidine in a mixture of N-␣-acetylarginine ؉ N-␣-acetyllysine, bovine lens proteins (BLP), and lysozyme; the amounts measured with STGP gel were higher than those with LTGP gel. Reactive oxygen species scavengers decreased the formation of pentosidine. Pentosidine was also formed in BLP when incubated with water-insoluble proteins extracted from aged or brunescent human lenses. Early glycated proteins from aged or diabetic lenses were bound to a boronate affinity column, the protein-containing gel was incubated with BLP, and pentosidine was measured in the incubation mixtures. With this method we found that diabetic lens proteins produced more pentosidine on BLP than did aged lens proteins. Further investigation indicates that two and three carbon carbohydrates possibly formed from oxidative cleavage of early glycation products are involved in pentosidine formation. Based on our findings, we propose a novel pathway for pentosidine formation on native proteins from glycated proteins.

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“…This glycation is not random, but it depends on the structural configuration and (or) physical locations of the target proteins [86,87]. The AGEs produced by the reaction between MG and arginine are hydroimidazolone Nε-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine and argpyrimidine [88], whereas the AGE, Nε-carboxyethyllysine (CEL) [89,90] is formed when MG reacts with lysine. Further crosslinking of these AGEs produces fluorescent products such as pentosidine and cross-line, and non-fluorescent ones such as argpyrimidine, methylglyoxal-lysine dimer (MOLD), glyoxal-lysine dimer (GOLD) and imidazolones [91,92].…”

Section: Advanced Glycation Endproductsmentioning

confidence: 99%

Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

Dhar¹,

Desai²

2012

Pharmacology

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Protein Modification by Methylglyoxal: Chemical Nature and Synthetic Mechanism of a Major Fluorescent Adduct

Cited by 257 publications

References 53 publications

NADPH-dependent Reductases Involved in the Detoxification of Reactive Carbonyls in Plants

NADPH-dependent Reductases Involved in the Detoxification of Reactive Carbonyls in Plants

Early Glycation Products Produce Pentosidine Cross-links on Native Proteins

Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

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