Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress - PubMed (original) (raw)

Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress

Naila Rabbani et al. Biochem Soc Trans. 2008 Oct.

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.

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Figures

Figure 1

Figure 1. Major pathways for the formation of AGEs in physiological systems and precursor dicarbonyl metabolites

(a) Formation of early and advanced glycation adducts from glucose and glycolytic intermediates and products of lipid peroxidation. (b) Physiological reactive dicarbonyl-glycating agents.

Figure 2

Figure 2. Protein glycation adduct residues

(a) Early glycation adducts. (b) AGEs. For the corresponding free adducts at physiological pH, the N-terminal amino group is protonated −NH3+ and the C-terminal carbonyl is a carboxylate −CO2− moiety. DOLD, 3-deoxyglucosone-derived lysine dimer; GOLD, glyoxal-derived lysine dimer; MOLD, methylglyoxal-derived lysine dimer.

Figure 3

Figure 3. The enzymatic defence against glycation

(a) Metabolism of glyoxal and MG by the glyoxalase system. (b) Metabolism of 3DG by 3-deoxyglucosone reductase, an AKRd. (c) Metabolism of 3DG by 3-deoxyglucosone dehydrogenase. (d, e) Repair of early glycated proteins by Amadoriase and fructosamine-3-phosphokinase.

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