ALBUMIN MODIFICATION IN HEMOCHROMATOSIS

André SILVA^1,2, Eduardo RAMOS¹, Graça PORTO^3,4,5, Maria RANGEL²

¹LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
²LAQV-REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
³Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
⁴I3S, Instituto de Investigação e Inovação em Saúde, Porto, Portugal
⁵Departamento de Hematologia, Centro Hospitalar Universitário de Santo António, Porto, Portugal

NTBI is present under the form of a heterogenous mixture of species, composed of Low Molecular Weight species (LMW-NTBI) and High Molecular Weight species (HMW-NTBI). Albumin (HSA) has been proposed as the main candidate for the formation of HMW-NTBI, with protein post-translational modifications (PTMs) playing a role in this interaction.

Here in, we aimed to study HSA PTMs by mass spectrometry, namely glycation and oxidation, to evaluate their contribution to NTBI levels in blood serum samples. Serum from individuals homozygous for the p.C282Y variant in HFE, as well as samples from healthy blood donors, were utilized to characterize HSA PTMs and study their correlation with NTBI levels.

Results show that glycation levels were altered in HH patients, which showed higher PTM site occupancy values in both K233 and K525 in comparison with controls. HSA oxidation was also altered in HH patients, namely those under intensive treatment, with significantly higher oxidation values for M87 (2.6%) in comparison with controls (1.0%). Glycation values for K525 and oxidation values for M87 and M298 showed a positive correlation with NTBI levels. These results may reveal the unspecific iron binding sites in HSA. Additionally, these results positively indicate an interaction between HSA and serum iron levels, supporting the role of HSA in NTBI speciation, in vivo.

Funding: The work was financially supported by the eQuaNTI project (2022.06328.PTDC), funded by FCT/MCTES through national funds.

Acknowledgments: FCT/MCTES through the project UIDB/50006/2020 | UIDP/50006/2020.