The Maillard Reaction as a Basis for a Theory of Aging

Peroxidized phospholipid-mediated cytotoxity is involved in the pathophysiology of a number of diseases [i.e., the abnormal increase of phosphatidylcholine hydroperoxide (PCOOH) found in the plasma of type 2 diabetic patients]. The PCOOH accumulation may relate to Amadoriglycated phosphatidylethanolamine (deoxy-D-fructosyl PE, or Amadori-PE), because Amadori-PE causes oxidative stress. However, lipid glycation inhibitor has not been discovered yet because of the lack of a lipid glycation model useful for inhibitor screening. We optimized and developed a lipid glycation model considering various reaction conditions (glucose concentration, temperature, buffer type, and pH) between PE and glucose. Using the developed model, various protein glycation inhibitors (aminoguanidine, pyridoxamine, and carnosine), antioxidants (ascorbic acid, atocopherol, quercetin, and rutin), and other food compounds (L-lysine, L-cysteine, pyridoxine, pyridoxal, and pyridoxal 59-phosphate) were evaluated for their antiglycative properties. Pyridoxal 59-phosphate and pyridoxal (vitamin B 6 derivatives) were the most effective antiglycative compounds. These pyridoxals could easily be condensed with PE before the glucose/ PE reaction occurred. Because PE-pyridoxal 59-phosphate adduct was detectable in human red blood cells and the increased plasma Amadori-PE concentration in streptozotocininduced diabetic rats was decreased by dietary supplementation of pyridoxal 59-phosphate, it is likely that pyridoxal 59-phosphate acts as a lipid glycation inhibitor in vivo, which possibly contributes to diabetes prevention.-Higuchi, O., K. Nakagawa, T. Tsuzuki, T. Suzuki, S. Oikawa, and T. Miyazawa. Aminophospholipid glycation and its inhibitor screening system: a new role of pyridoxal 59-phosphate as the inhibitor. Lipid peroxidation plays a role in the pathophysiology of atherogenesis, diabetes, aging, and other conditions (1). To determine lipid hydroperoxides as a primary oxidation product, we established a chemiluminescence detectionliquid chromatography (LC) method (2). Using this method, it was confirmed that plasma phosphatidylcholine hydroperoxide (PCOOH) abnormally increases in hyperlipidemic (3) and in type 2 diabetic (4) patients. Hence, we hypothesized that PCOOH-mediated cytotoxity is closely involved in the pathophysiology of these diseases.Recently, while investigating why PCOOH increases in diabetic plasma, we found that diabetic plasma contained an abnormal amount of glycated lipid. The glycated lipid was identified as an Amadori product of phosphatidylethanolamine (deoxy-D-fructosyl phosphatidylethanolamine, or Amadori-PE) (Fig. 1) by LC online with hybrid quadrupole/linear ion-trap mass spectrometry (QTRAP LC/MS/MS) (5, 6). Amadori-PE generates reactive oxygen species and thereby triggers lipid peroxidation (7). Therefore, it is likely that PE is exposed to glycation under hyperglycemic conditions, yielding Amadori-PE in vivo. Amadori-PE causes oxidative stress (i.e., PCOOH) (5, 6), leading to a disorder of cellular integrit...

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“…For example, amino compounds (e.g., alanine) can react with glucose and minimize the potentially deleterious consequences of hyperglycemia (36).…”

Section: Discussionmentioning

confidence: 99%

Aminophospholipid glycation and its inhibitor screening system: a new role of pyridoxal 5′-phosphate as the inhibitor

Higuchi

Nakagawa

Tsuzuki

et al. 2006

Journal of Lipid Research

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“…The cross-linking of long-lived proteins, such as collagen and lens crystallins, correlates with aging and diabetic processes [1]. Glycation, which proceeds during normal aging, and at accelerated rates in diabetes, is involved in structural and functional alterations of proteins and other cellular components.…”

Section: Introductionmentioning

confidence: 99%

Specific detections of the early process of the glycation reaction by fructose and glucose in diabetic rat lens

et al. 1998

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The glycation reaction by fructose, as well as that by glucose, in control and diabetic rat lens was analyzed by using antibodies which specifically recognize adducts of lysine with fructose and with glucose. Levels of fructose adducts in diabetic rat lens were 2.5 times that of the control, and correlated with sorbitol levels. This was mainly due to enhanced glycation of L Land Q Q-crystallins by fructose under diabetic conditions. These data suggest that glycation by fructose may also play a role in cataract formation under conditions of diabetes and aging.z 1998 Federation of European Biochemical Societies.

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“…The levels of AGEs increase substantially in diabetic plasma due to the hyperglycemic condition. Factors such as oxidative stress, overnutrition, and foods rich in glycating agents promote the formation of AGEs even in nondiabetic condition (4). Oral AGEs foster insulin resistance and diabetes by down-regulation of anti-AGE receptor-1(AGER1), sirtuin 1, and up-regulation of receptor for AGEs (RAGE) (5).…”

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confidence: 99%

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

Korwar

Vannuruswamy

Jagadeeshaprasad

et al. 2015

Molecular & Cellular Proteomics

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Human serum albumin is one of the most abundant plasma proteins that readily undergoes glycation, thus glycated albumin has been suggested as an additional marker for monitoring glycemic status. Hitherto, only Amadori-modified peptides of albumin were quantified. In this study, we report the construction of fragment ion library for Amadori-modified lysine (AML), N()-(carboxymethyl)lysine (CML)-, and N()-(carboxyethyl)lysine (CEL)-modified peptides of the corresponding synthetically modified albumin using high resolution accurate mass spectrometry (HR/AM). The glycated peptides were manually inspected and validated for their modification. Further, the fragment ion library was used for quantification of glycated peptides of albumin in the context of diabetes. Targeted Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH) analysis in pooled plasma samples of control, prediabetes, diabetes, and microalbuminuria, has led to identification and quantification of 13 glycated peptides comprised of four AML, seven CML, and two CEL modifications, representing nine lysine sites of albumin. Five lysine sites namely K549, K438, K490, K88, and K375, were observed to be highly sensitive for glycation modification as their respective m/z showed maximum fold change and had both AML and CML modifications. Thus, peptides involving these lysine sites could be potential novel markers to assess the degree of glycation in diabetes. Molecular & Cellular Proteomics

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The Maillard Reaction as a Basis for a Theory of Aging

Cited by 72 publications

References 39 publications

Aminophospholipid glycation and its inhibitor screening system: a new role of pyridoxal 5′-phosphate as the inhibitor

Aminophospholipid glycation and its inhibitor screening system: a new role of pyridoxal 5′-phosphate as the inhibitor

Specific detections of the early process of the glycation reaction by fructose and glucose in diabetic rat lens

Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE

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