Carbamylation of human serum albumin generates high-molecular weight aggregates: fine characterization by multi-spectroscopic methods and electron microscopy
| Autor: | Zarina Arif, Shireen Naaz Islam, Khursheed Alam, Faizan Abul Qais, Asim Badar |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Amyloid
Serum Albumin Human 02 engineering and technology Biochemistry Protein Aggregates 03 medical and health sciences chemistry.chemical_compound Structural Biology medicine Humans Molecular Biology Cyanates 030304 developmental biology Homocitrulline 0303 health sciences Protein Carbamylation Chemistry Spectrum Analysis Albumin General Medicine 021001 nanoscience & nanotechnology Human serum albumin Isocyanic acid Congo red Microscopy Electron Urea Biophysics 0210 nano-technology Potassium cyanate Macromolecule medicine.drug |
| Zdroj: | International Journal of Biological Macromolecules. 164:2380-2388 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2020.08.083 |
| Popis: | Carbamylation is the non-enzymatic reaction between isocyanic acid and macromolecules (mainly proteins) which results in carbamylation-derived products (CDPs) generation, wherein the macromolecules show altered structure and function. In this study, we examined the modifications caused in human serum albumin (HSA) upon interaction with potassium cyanate (KCNO). HSA was incubated with varying concentrations of KCNO for 6 h at 37 °C. The resultant product was characterized by biochemical and biophysical techniques. Among other changes, the carbamylated-HSA showed homocitrulline generation (LC-MS), increase in mass (DLS), and amyloidogenic aggregate formation (Congo red, SEM, TEM). The Gibb's free energy was calculated to be −2.91 to −3.95 kcal mol−1, suggesting that the binding was spontaneous and energetically favourable. The results indicate that in chronic kidney disease patients, elevated levels of isocyanic acid (formed from urea) may modify the albumin structure and lead to its conversion into amyloidogenic aggregates, thus accelerating kidney damage. |
| Databáze: | OpenAIRE |
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