scispace - formally typeset
Search or ask a question
Author

Antony C. McLellan

Bio: Antony C. McLellan is an academic researcher from University of Essex. The author has contributed to research in topics: Methylglyoxal & Glyoxalase system. The author has an hindex of 10, co-authored 13 publications receiving 1907 citations.

Papers
More filters
Journal ArticleDOI
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

Journal ArticleDOI
TL;DR: The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus, patients with non-insulin-dependent Diabetes mellitus and 21 normal healthy control subjects.
Abstract: 1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

556 citations

Journal ArticleDOI
TL;DR: The concentration of methylglyoxal in whole blood from normal healthy human individuals was 256 +/- 92 and that from diabetic patients was 479 +/- 49, showing a significant increase in diabetes mellitus (P < 0.01; Mann-Whitney U test).

226 citations

Journal ArticleDOI
TL;DR: Retinopathy, neuropathy and nephropathy correlated with duration of diabetes, but retinopathy also correlated positively with haemoglobin A1C in diabetic patients and the role of these factors in the development of diabetic complications and the prospective prevention of diabetes complications by supplementation of reduced glutathione and/or alpha-oxoaldehyde-scavenging agents now deserve investigation.
Abstract: 1. Multiple logistic regression analysis of biochemical and clinical variables in diabetic patients was performed to identify those associated with the presence of diabetic complications (retinopathy, neuropathy and nephropathy). 2. The presence of diabetic complications correlated positively with duration of diabetes and patients age and negatively with the concentration of reduced glutathione in erythrocytes. Individually, retinopathy, neuropathy and nephropathy correlated with duration of diabetes, but retinopathy also correlated positively with haemoglobin A1C in diabetic patients. In insulin-dependent patients, the concentration of methylglyoxal was also in the logistic model for retinopathy and diabetic complications, but the logistic regression coefficient was not significant. 3. Multiple linear regression analysis indicated that erythrocyte reduced glutathione concentration correlated negatively with D-lactate concentration and positively with duration of diabetes in insulin-dependent patients and correlated negatively with glucose concentration in non-insulin-dependent diabetic patients. 4. In non-diabetic subjects, erythrocyte glyoxalase I activity correlated positively with methylglyoxal concentration. There was no similar correlation in diabetic patients. In insulin-dependent patients, methylglyoxal concentration correlated positively with duration of diabetes. 5. Glyoxal and methylglyoxal are detoxified by the glyoxalase system with reduced glutathione as co-factor. The concentration of reduced glutathione may be decreased by oxidative stress and by decreased in situ glutathione reductase activity in diabetes mellitus. A reduced concentration of reduced glutathione may predispose diabetic patients to oxidative damage and to alpha-oxoaldehydemediated glycation by decreasing the in situ glyoxalase I activity. Recent studies of vascular endothelial cells in vitro have suggested that alpha-oxoaldehydes detoxified by glyoxalase I are the major precursors of advanced glycation end products implicated in the development of diabetic complications. The role of these factors in the development of diabetic complications and the prospective prevention of diabetic complications by supplementation of reduced glutathione and/or alpha-oxoaldehyde-scavenging agents now deserve investigation.

133 citations

Journal ArticleDOI
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


Cited by
More filters
Journal ArticleDOI
01 Jun 2005-Diabetes
TL;DR: What was learned about the pathobiology of diabetic complications starting with that 1966 Science paper and continuing through the end of the 1990s are described, including a unified mechanism that links together all of the seemingly unconnected pieces of the puzzle.
Abstract: It’s a great honor to join the exceptional club of Banting Award winners, many of whom were my role models and mentors. In addition, giving the Banting Lecture also has a very personal meaning to me, because without Frederick Banting, I would have died from type 1 diabetes when I was 8 years old. However, it was already apparent at the time I was diagnosed that for too many people like me, Banting’s discovery of insulin only allowed them to live just long enough to develop blindness, renal failure, and coronary disease. For example, when I started college, the American Diabetes Association’s Diabetes Textbook had this to say to my parents: “The person with type 1 diabetes can be reassured that it is highly likely that he will live at least into his 30s.” Not surprisingly, my parents did not find this particularly reassuring. At the same time we were reading this in 1967, however, the first basic research discovery about the pathobiology of diabetic complications had just been published in Science the previous year. In my Banting Lecture today, I am thus going to tell you a scientific story that is also profoundly personal. I’ve divided my talk into three parts. The first part is called “pieces of the puzzle,” and in it I describe what was learned about the pathobiology of diabetic complications starting with that 1966 Science paper and continuing through the end of the 1990s. In the second part, I present a unified mechanism that links together all of the seemingly unconnected pieces of the puzzle. Finally, in the third part, I focus on three examples of novel therapeutic approaches for the prevention and treatment of diabetic complications, which are all based on the new paradigm of a unifying mechanism for the pathogenesis of diabetic complications. …

4,691 citations

Journal ArticleDOI
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

Journal ArticleDOI
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

Journal ArticleDOI
TL;DR: Aqueous V(III) Chemistry 877 6.2.1.
Abstract: 6.1.2. Aqueous V(III) Chemistry 877 6.1.3. Oxidation State of Vanadium in Tunicates 878 6.1.4. Uptake of Vanadate into Tunicates 879 6.1.5. Vanadium Binding Proteins: Vanabins 879 6.1.6. Model Complexes and Their Chemistry 880 6.1.7. Catechol-Based Model Chemistry 880 6.1.8. Vanadium Sulfate Complexes 881 6.2. Fan Worm Pseudopotamilla occelata 883 7. Vanadium Nitrogenase 883 7.1. Nitrogenases 883 7.2. Biochemistry of Nitrogenase 884 7.3. Clusters in Nitrogenase and Model Systems: Structure and Reactivity 885

1,184 citations

Journal ArticleDOI
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