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The Modification of Lysine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
The reaction of glyceraldehyde with carbonmonoxyhemoglobin S has been explored by Acharya and Manning.113 This reaction was performed with 0.010 M glyceraldehyde in phosphate-buffered saline, pH 7.4, and the resultant Schiff bases were stabilized by reduction with sodium borohydride. Using radiolabeled glyceraldehyde, these investigators were able to obtain support for the concept that there is selectivity in the reaction of sugar aldehydes with hemoglobin. The reaction product between glyceraldehyde and hemoglobin S did have stability properties without reduction that were not consistent with only Schiff base products. These investigators suggested that the glyceraldehyde-hemoglobin Schiff base could undergo an Amadori rearrangement (Figure 43) to form a stable ketoamine adduct which could be reduced with sodium borohydride to form a product identical to that obtained by direct reduction of the Schiff base. In a subsequent study, these investigators did show that the glyceraldehyde-hemoglobin S Schiff base could rearrange to form a ketamine via an Amadori rearrangement.114 These investigators were able to use reaction with phenylhydrazine to detect the protein-bound ketamine adduct as shown in Figure 44.
Fibrinolysis and Diabetes Mellitus
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Michael W. Mansfield, Peter J. Grant
Protein glycosylation is due to the binding of glucose to protein by a nucleophilic reaction resulting in a Schiff base that then undergoes an Amadori rearrangement.81 The extent to which protein glycosylation occurs is dependent upon the duration and magnitude of protein exposure to glucose. This binding may be reversible, giving rise to early glycosylation products such as glycosylated hemoglobin, which is used as a measure of glycemic control over the preceding 6 to 8 weeks, the time taken by the early glycosylation reaction to reach equilibrium. Glucose binds particularly at the free ∊-amino group residue of protein lysine residues.81
Cognitive Dysfunction and Depression in Older Adults with Diabetes
Published in Medha N. Munshi, Lewis A. Lipsitz, Geriatric Diabetes, 2007
Chronic hyperglycemia is a key feature for elderly people afflicted by DM. Early reaction between glucose and protein amino acids proceeds from nonenzymatic glycosylation (post-translational modification) to reversible Schiff bases, and to stable, covalently bonded Amadori rearrangement products (33). Over weeks and months, these early products evolve further chemical reactions, including rearrangement, dehydration, cleavage, and addition, into irreversibly bonded advanced glycation end products (AGEs) (34). Immunohistochemically, AGE modification was identified in both senile plaques and neurofibrillary tangles (35). It was also reported that AGE-modified Aβ promotes Aβ aggregation, thus contributing to amyloidosis in AD (36).
In silico prediction of post-translational modifications in therapeutic antibodies
Published in mAbs, 2022
Glycation is a non-enzymatic modification, where amino groups at lysine (Lys) and arginine residues or the N-terminal are glycated by reducing sugars such as glucose.89 The Schiff base is formed after a condensation reaction between the aldehydes of the reducing sugars and the amine groups of Lys residues (Figure 3(a)). Schiff base formation is reversible; however, the multistep Amadori rearrangement can generate more stable ketoamines (Figure 3(b)).90 Glycated Lys residues can further degrade to form advanced glycation end products,91 which can cause an immunogenic response. Lys glycation typically occurs during long-term storage in formulations, cell culture, and in vivo.92 Disaccharides in formulations can degrade to form reducing sugars, leading to glycation during storage.92 During cell culture, a high glucose concentration can accelerate Lys glycation and reduce protein yield.89 The effects of Lys glycation on antigen binding varies from decreased binding affinity93 to minimal change in binding affinity.94 Lys glycation can increase protein aggregation by affecting the net surface charge, reducing the electrostatic repulsion between antibodies.95 Forced glycation is used to identify liable Lys residues by incubating the IgG with high concentrations of reducing sugars (e.g., glucose) at high temperatures.92 Forced glycation in citrate buffers correlates well with glycation during cell culture.96
Acrylamide in foods: from regulation and registered levels to chromatographic analysis, nutritional relevance, exposure, mitigation approaches, and health effects
Published in Toxin Reviews, 2022
Mónica Quesada-Valverde, Graciela Artavia, Fabio Granados-Chinchilla, Carolina Cortés-Herrera
As a means of preservation or improving sensory properties, several foods are subjected to thermal processing, promoting chemical and physical changes (Teodorowicz et al.2017). Maybe, the most relevant interactions occur during glycation reactions (i.e. as a whole known as Maillard) (Teodorowicz et al.2017). The Maillard reaction produces aromatic and colored compounds (Tamanna and Mahmood 2015). Maillard reaction products (MRP) can generate positive and adverse health effects (Teodorowicz et al.2017). At the first stage of the reaction, sugars and amino acids condense and following this condensation, the Amadori rearrangement and 1-amino-1-deoxy-2-ketoses arise (Tamanna and Mahmood 2015). Common foods where ACR has been chiefly described include milk, soybean, pasta, meat, coffee, and plant-derived foods (Tamanna and Mahmood 2015).
Quantitative analysis of glycation and its impact on antigen binding
Published in mAbs, 2018
Jingjie Mo, Renzhe Jin, Qingrong Yan, Izabela Sokolowska, Michael J. Lewis, Ping Hu
Glycation refers to the nonenzymatic reaction between sugars and proteins as originally described by Maillard.1 Glycation is triggered by the exposure of proteins to reducing sugars such as glucose, fructose and galactose, which typically react with the side chains of lysine residues or the N-termini of proteins to form a Schiff base between the aldehyde groups of the sugars and the primary amines of the protein. Formation of the Schiff base intermediate is reversible, but this intermediate can be converted into a more stable ketoamine adduct through an Amadori rearrangement.2–4 Glycated antibodies have been detected in vivo,5–7 and glycation has been observed during antibody production.8,9 Glycation alters the charge profile of therapeutic proteins,10 and could potentially affect the stability11,12 and potency of the protein.13–18