Clinical, pathophysiological and structure/function consequences of modification of albumin by Amadori-glucose adducts

Cohen, Morrel H.

doi:10.1016/j.bbagen.2013.04.024

Cited by 23 publications

(17 citation statements)

References 99 publications

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“…HSA contains a total of 58 surfaceexposed lysine residues rendering their accessibility for interaction with various blood constituents including glucose. Only a few lysines are surface accessible to undergo glycation modification, resulting in impaired antioxidant and cargo capabilities of HSA (41). Similar to HSA modification by malondialdehyde (42), a highly positive local environment expedites glycation reaction, determining the site specificity of glycation.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Albumin comprises almost two-thirds of total serum protein and accounts for over 80% of total glycated serum proteins (52). HPLC tandem mass spectrometry of human plasma using [ 13 C 6 ]glucose labeling has identified 35 glycation sites on albumin (53).…”

Section: Glycated Albuminmentioning

confidence: 99%

“…A number of glycated albumin assays are commercially available, but these lack standardization and values vary widely among methods (54). Specifically, the reference intervals have considerable variation depending on the method and range from 0.8–1.4% to 18–22% (52,54). A U.S. Food and Drug Administration–approved method for glycated albumin measurement manufactured by Diazyme Laboratories (Poway, CA) is commercially available (55).…”

Section: Glycated Albuminmentioning

confidence: 99%

Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions

2016

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“…Several reports indicate that AGE products are able at least in vitro to induce activation of various cells including platelets (16,17). In addition to classical glycemic indices, several recent reports indicated that glycated albumin is a relevant and practical biomarker for the progression of diabetic atherosclerosis (18)(19)(20).…”

mentioning

confidence: 99%

Glycated Albumin With Loss of Fatty Acid Binding Capacity Contributes to Enhanced Arachidonate Oxygenation and Platelet Hyperactivity: Relevance in Patients With Type 2 Diabetes

et al. 2014

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High plasma concentrations of nonesterified fatty acids (NEFAs), transported bound to serum albumin, are associated with type 2 diabetes (T2D). The effects of albumin on platelet function were investigated in vitro. Modifications of albumin, such as those due to glycoxidation, were found in patients with T2D, and the consequences of these modifications on biological mechanisms related to NEFA handling were investigated. Mass spectrometry profiles of albumin from patients with T2D differed from those from healthy control subjects. Diabetic albumin showed impaired NEFA binding capacity, and both structural and functional alterations could be reproduced in vitro by incubating native albumin with glucose and methylglyoxal. Platelets incubated with albumin isolated from patients with T2D aggregated approximately twice as much as platelets incubated with albumin isolated from healthy control subjects. Accordingly, platelets incubated with modified albumin produced significantly higher amounts of arachidonate metabolites than did platelets incubated with control albumin. We concluded that higher amounts of free arachidonate are made available for the generation of active metabolites in platelets when the NEFA binding capacity of albumin is blunted by glycoxidation. This newly described mechanism, in addition to hypoalbuminemia, may contribute to platelet hyperactivity and increased thrombosis, known to occur in patients with T2D.

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Clinical, pathophysiological and structure/function consequences of modification of albumin by Amadori-glucose adducts

Cited by 23 publications

References 99 publications

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

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

Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions

Glycated Albumin With Loss of Fatty Acid Binding Capacity Contributes to Enhanced Arachidonate Oxygenation and Platelet Hyperactivity: Relevance in Patients With Type 2 Diabetes

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