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Effect of different glycation agents on Cu(II) binding to human serum albumin, studied by liquid chromatography, nitrogen microwave-plasma atomic-emission spectrometry, inductively-coupled-plasma mass spectrometry, and high-resolution molecular-mass spectrometry

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Abstract

The ability of human serum albumin to capture unbound copper under different clinical conditions is an important variable potentially affecting homeostasis of this element. Here, we propose a simple procedure based on size-exclusion chromatography with on-line UV and nitrogen microwave-plasma atomic-emission spectrometry (MP-AES) for quantitative evaluation of Cu(II) binding to HSA upon its glycation in vitro. The Cu-to-protein molar ratio for non-glycated albumin was 0.98 ± 0.09; for HSA modified with glyoxal (GO), methylglyoxal (MGO), oxoacetic acid (GA), and glucose (Glc), the ratios were 1.30 ± 0.22, 0.72 ± 0.14, 0.50 ± 0.06, and 0.95 ± 0.12, respectively. The results were confirmed by using ICP-MS as an alternative detection system. A reduced ability of glycated protein to coordinate Cu(II) was associated with alteration of the N-terminal metal-binding site during incubation with MGO and GA. In contrast, glycation with GO seemed to generate new binding sites as a result of tertiary structural changes in HSA. Capillary reversed-phase liquid chromatography with electrospray-ionization quadrupole-time-of-flight tandem mass spectrometry enabled detection and identification of Cu(II) coordinated to the N-terminal metal-binding site (Cu(II)–DAHK) in all tryptic digests analyzed. This is the first report confirming Cu(II)–DAHK species in HSA by means of high-resolution tandem mass spectrometry, and the first report on the use of MP-AES in combination with chromatographic separation.

General scheme designed to study Cu(II) binding to glycated versus non-glycated albumin and MPAESinstrumentation used

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Acknowledgments

The financial support from National Council of Science and Technology, Mexico (CONACYT), projects 178553,187749, 123732, is gratefully acknowledged. The authors also thank for the support from the Ministry of Public Education (PROMEP), project UGTO-PTC-327.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Chemistry Department, Division of Natural and Exact Sciences, University of Guanajuato, L. de Retana 5, 36000, Guanajuato, Mexico

    Alma Rosa Corrales Escobosa, Katarzyna Wrobel, Eunice Yanez Barrientos, Sarahi Jaramillo Ortiz, Alejandra Sarahi Ramirez Segovia & Kazimierz Wrobel

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  1. Alma Rosa Corrales Escobosa
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  2. Katarzyna Wrobel
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  3. Eunice Yanez Barrientos
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Correspondence to Kazimierz Wrobel.

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Corrales Escobosa, A.R., Wrobel, K., Yanez Barrientos, E. et al. Effect of different glycation agents on Cu(II) binding to human serum albumin, studied by liquid chromatography, nitrogen microwave-plasma atomic-emission spectrometry, inductively-coupled-plasma mass spectrometry, and high-resolution molecular-mass spectrometry. Anal Bioanal Chem 407, 1149–1157 (2015). https://doi.org/10.1007/s00216-014-8335-1

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