The Modification of Lysine
Roger L. Lundblad in 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.
Cognitive Dysfunction and Depression in Older Adults with Diabetes
Medha N. Munshi, Lewis A. Lipsitz in 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).
Fibrinolysis and Diabetes Mellitus
Pia Glas-Greenwalt in Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
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
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
In silico prediction of post-translational modifications in therapeutic antibodies
Published in mAbs, 2022
The use of SASA to identify liable residues is a popular approach.27 High solvent exposure is a prerequisite for Lys glycation, but not all exposed Lys residues are glycated.96 Lys glycation is also influenced by flanking residues (i.e., polar, 97 acidic, and basic residues92), three-dimensional structure, and pKa of Lys residues.90 Neighboring Asp and His residues can slow Schiff base formation; however, flanking His and Asp residues can promote Amadori rearrangement by acting as proton donors and acceptors (Figure 3(b)).90,97 Liable motifs for glycation include KD, KXD, KXK, and KXE.96 Structure-based approaches can identify acidic residues that are not part of motifs, but are close enough to catalyze glycation.98 For example, Zhang et al. reported glycation at light chain (LC)-Lys49, which was 11 Å apart from LC-Asp31.97 They suggested that the flexibility of Lys and Asp side-chains promoted Amadori rearrangement by reducing the distance between LC-Lys49 and LC-Asp31.97
Related Knowledge Centers
- Acid Catalysis
- Aldose
- Amine
- Carbohydrate Chemistry
- Isomerization
- Glycoside
- Organic Reaction
- Glycosylamine
- Glycated Hemoglobin
- Advanced Glycation End-Product