Author
Marie E. Westwood
Bio: Marie E. Westwood is an academic researcher from University of Essex. The author has contributed to research in topics: Methylglyoxal & Serum albumin. The author has an hindex of 7, co-authored 7 publications receiving 1203 citations.
Papers
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TL;DR: The formation of methylglyoxal-modified proteins involves glycoxidation leading to advanced glycation end product-like fluorescence and is expected to be increased in diabetes mellitus and may be linked to the development of diabetic complications.
691 citations
TL;DR: Analysis of amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal and by glucose-derived advanced glycation endproducts suggested that AGE formed from glucose-modified proteins and AGE-like compounds formed from methyl glyoxal- modified proteins may both be signals for recognition and degradation of senescent macromolecules.
Abstract: The amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal (MG-SA) and by glucose-derived advanced glycation endproducts (AGE-SA) were investigated. Methylglyoxal selectively modified arginine residues at low concentration (1 mM); at high methylglyoxal concentration (100 mM), the extent of arginine modification increased and lysine residues were also modified. Both arginine and lysine residues were modified in AGE-SA. Analytical gel filtration HPLC of serum albumin derivatives suggested that the proportion of dimers and oligomers increased with modification in both low and highly modified MG-SA and AGE-SA derivatives relative to unmodified serum albumins. In SDS-PAGE analysis, dimers and oligomers of low-modified MG-SA were dissociated into monomers, but not in highly modified MG-SA. MG-SA had increased anodic electrophoretic mobility under nondenaturing conditions at pH 8.6, indicating an increased net negative charge, which increased with extent of modification; highly modified MG-SA and AGE-SA had similar high electrophoretic mobilities. MG-SA derivatives were fluorescent: the fluorescence was characteristic of the arginine-derived imidazolone N delta-(5-methyl-4-imidazolon-2-yl)ornithine, but other fluorophores were also present. AGE-SA had similar fluorescence, attributed, in part, to glucose-derived imidazolones. AGE formed from glucose-modified proteins and AGE-like compounds formed from methylglyoxal-modified proteins may both be signals for recognition and degradation of senescent macromolecules.
223 citations
TL;DR: The irreversible modification ofprotein by methylglyoxal is a potent signal for the degradation of proteins by monocytic cells in which the arginine derivative, Ndelta-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine, is the receptor recognition factor.
102 citations
TL;DR: Methylglyoxal binds and irreversibly modifies arginine and lysine residues in bovine serum albumin under physiological conditions, producing a protein with an increased net negative charge at physiological pH.
98 citations
TL;DR: Human serum albumin modified with 1-2 methylglyoxal residues per molecule of protein (MGmin-HSA) stimulated the synthesis and secretion of interleukin 1 beta (IL-1 beta) from human monocytic THP-1 cells in vitro.
65 citations
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TL;DR: This integrating paradigm provides a new conceptual framework for future research and drug discovery in diabetes-specific microvascular disease and seems to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain.
Abstract: Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage, and diabetes-accelerated atherosclerosis leads to increased risk of myocardial infarction, stroke and limb amputation. Four main molecular mechanisms have been implicated in glucose-mediated vascular damage. All seem to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain. This integrating paradigm provides a new conceptual framework for future research and drug discovery.
8,289 citations
TL;DR: Because of the emerging evidence about the adverse effects of AGEs on the vasculature of patients with diabetes, a number of different therapies to inhibit A GEs are under investigation.
Abstract: Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of athe...
2,054 citations
TL;DR: The chemistry of glycation and AGEs is introduced and the mechanisms by which they mediate their toxicity are examined and the role of A GEs in the pathogenesis of retinopathy, cataract, atherosclerosis, neuropathy, nephropathy, diabetic embryopathy and impaired wound healing are considered.
1,316 citations
TL;DR: Alpha-Oxoaldehydes were formed in early glycation from the degradation of glucose and Schiff's base adduct, which suggests that short periods of hyperglycaemia, as occur in impaired glucose tolerance, may be sufficient to increase the concentrations of alpha-oxoaldeHydes in vivo.
Abstract: The glycation of proteins by glucose has been linked to the development of diabetic complications and other diseases. Early glycation is thought to involve the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff's base and fructosamine adducts. The formation of the alpha-oxoaldehydes, glyoxal, methylglyoxal and 3-deoxyglucosone, in early glycation was investigated. Glucose (50 mM) degraded slowly at pH 7.4 and 37 degrees C to form glyoxal, methylglyoxal and 3-deoxyglucosone throughout a 3-week incubation period. Addition of t-BOC-lysine and human serum albumin increased the rate of formation of alpha-oxoaldehydes - except glyoxal and methylglyoxal concentrations were low with albumin, as expected from the high reactivity of glyoxal and methylglyoxal with arginine residues. The degradation of fructosyl-lysine also formed glyoxal, methylglyoxal and 3-deoxyglucosone. alpha-Oxoaldehyde formation was dependent on the concentration of phosphate buffer and availability of trace metal ions. This suggests that alpha-oxoaldehydes were formed in early glycation from the degradation of glucose and Schiff's base adduct. Since alpha-oxoaldehydes are important precursors of advanced glycation adducts, these adducts may be formed from early and advanced glycation processes. Short periods of hyperglycaemia, as occur in impaired glucose tolerance, may be sufficient to increase the concentrations of alpha-oxoaldehydes in vivo.
1,116 citations
TL;DR: In this paper, a complex relationship of the chemistry, biology, and pathology of browning products and the impact on human nutrition and health is discussed. And possible approaches to inhibiting browning reactions and preventing adverse effects of the browning during food processing and food consumption, including protection of heterocyclic amines by N-acetylcysteine, caffeine, chlorophyll, conjugated linoleic acid, lignin, and tea extracts, are also described.
Abstract: Enzymatic and nonenzymatic browning reactions of amino acids and proteins with carbohydrates, oxidized lipids, and oxidized phenols cause deterioration of food during storage and processing. The loss in nutritional quality and potentially in safety is attributed to destruction of essential amino acids, decrease in digestibility, inhibition of proteolytic and glycolytic enzymes, interaction with metal ions, and formation of antinutritional and toxic compounds. Studies in this area include influence of damage to essential amino acids on nutrition and food safety, nutritional damage as a function of processing conditions, and simultaneous formation of deleterious and beneficial compounds. These compounds include kidney-damaging Maillard reaction products, mutagens, carcinogens, antimutagens, antioxidants, antibiotics, and antiallergens. This overview covers the formation, nutrition, and safety of glycated proteins, characterized browning products, and heterocyclic amines. Possible approaches to inhibiting browning reactions and preventing adverse effects of browning during food processing and food consumption, including protection against adverse effects of heterocyclic amines by N-acetylcysteine, caffeine, chlorophyll, conjugated linoleic acid, lignin, and tea extracts, are also described. This research subject covers a complex relationship of the chemistry, biology, and pathology of browning products and the impact on human nutrition and health. Future study should differentiate antinutritional and toxicological relationships, define individual and combined potencies of browning products, and develop means to prevent the formation and to minimize the adverse manifestations of the most antinutritional and toxic compounds. Such studies should lead to better and safer foods and improved human health.
949 citations