TY - JOUR
T1 - Identification of a haptoglobin-hemoglobin complex in human blood plasma
AU - Sarpong-Kumankomah, Sophia
AU - Gailer, Jürgen
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/12
Y1 - 2019/12
N2 - Blood plasma metalloproteins that contain copper (Cu), iron (Fe), zinc (Zn) and/or other metals/metalloids are potential disease biomarkers because the bloodstream is in permanent contact with organs. Their quantification and/or the presence of additional metal-entities or the absence of certain metalloproteins in blood plasma (e.g. in Wilson's disease) may provide insight into the dyshomeostasis of the corresponding metal (s) to gain insight into disease processes. The first step in investigating if the determination of plasma metalloproteins is useful for the diagnosis of diseases is their definitive qualitative identification. To this end, we have added individual highly pure Cu, Fe or Zn-containing metalloproteins to plasma (healthy volunteer) and analyzed this mixture by size-exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic spectrometer (ICP-AES), simultaneously monitoring the emission lines of Cu, Fe and Zn. The results clearly identified ceruloplasmin (Cp), holo-transferrin (hTf), and α2-macroglobulin (α2M), which verifies our previous assignments. Interestingly, another major Fe-peak in plasma was identified as a haptoglobin (Hp)-hemoglobin (Hb) complex. This Hp-Hb complex is formed after Hb, which is released during the hemolysis of erythrocytes, binds to the plasma protein Hp. The Hp-Hb complex formation is known to be one of the strongest interactions in biochemistry (Kd ≈ 1 pmol/L) and is critical because it prevents kidney toxicity of free Hb. Hence, the simultaneous determination of Cp, hTf, α2M and the Hp-Hb complex in plasma in <25 min has the potential to provide new insight into disease processes associated with the bioinorganic chemistry of Cu, Fe and Zn.
AB - Blood plasma metalloproteins that contain copper (Cu), iron (Fe), zinc (Zn) and/or other metals/metalloids are potential disease biomarkers because the bloodstream is in permanent contact with organs. Their quantification and/or the presence of additional metal-entities or the absence of certain metalloproteins in blood plasma (e.g. in Wilson's disease) may provide insight into the dyshomeostasis of the corresponding metal (s) to gain insight into disease processes. The first step in investigating if the determination of plasma metalloproteins is useful for the diagnosis of diseases is their definitive qualitative identification. To this end, we have added individual highly pure Cu, Fe or Zn-containing metalloproteins to plasma (healthy volunteer) and analyzed this mixture by size-exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic spectrometer (ICP-AES), simultaneously monitoring the emission lines of Cu, Fe and Zn. The results clearly identified ceruloplasmin (Cp), holo-transferrin (hTf), and α2-macroglobulin (α2M), which verifies our previous assignments. Interestingly, another major Fe-peak in plasma was identified as a haptoglobin (Hp)-hemoglobin (Hb) complex. This Hp-Hb complex is formed after Hb, which is released during the hemolysis of erythrocytes, binds to the plasma protein Hp. The Hp-Hb complex formation is known to be one of the strongest interactions in biochemistry (Kd ≈ 1 pmol/L) and is critical because it prevents kidney toxicity of free Hb. Hence, the simultaneous determination of Cp, hTf, α2M and the Hp-Hb complex in plasma in <25 min has the potential to provide new insight into disease processes associated with the bioinorganic chemistry of Cu, Fe and Zn.
KW - Copper
KW - Haptoglobin
KW - Hemoglobin
KW - Iron
KW - Metalloproteins
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85071956326&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2019.110802
DO - 10.1016/j.jinorgbio.2019.110802
M3 - Article
C2 - 31514091
AN - SCOPUS:85071956326
SN - 0162-0134
VL - 201
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
M1 - 110802
ER -