A study of zinc distribution in human serum

doi:10.1016/S0006-3061(00)82019-0

Bioinorganic Chemistry

Volume 5, Issue 3, 1976, Pages 211-218

https://doi.org/10.1016/S0006-3061(00)82019-0 Get rights and content

Abstract

The partition of zinc in human serum between two major zinc-binding proteins, albumin and α₂-macroglobulin, was studied in 28 control subjects and in 156 hospitalized patients. Albumin-bound zinc was both the major and the more dynamic of the serum zinc components. Over a wide range of values the concentrations of albumin-bound zinc and total serum zinc were highly correlated (r=0.91) with each other, as were concentrations of albumin and albumin-bound zinc (r=0.69). α₁-Macroglobulin-bound zinc was not strongly correlated either with total serum zinc or with the serum concentration of α₂-macroglobulin. Twenty-four hour urinary excretion of zinc was not correlated with any of the serum zinc parameters. To a large extent it appears that total serum zinc concentration reflects serum albumin concentration.

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ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16–19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones.
Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19.
Quantitative prediction of electronic absorption spectra of copper(II)–bioligand systems: Validation and applications
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Citation Excerpt :
The small change in the absorption maximum going from [Cu(Gly)2] to [Cu(Gly)2(H2O)] is due to the long Cu–OH2 distance (2.376 Å experimental [98], and 2.434 Å calculated). Human serum albumin is involved in the transport of various metal ions such as Ni(II) [101], Zn(II) [102,103] and Cu(II) [104]. Two metal binding sites exist in its structure: the ATCUN (Amino Terminal Copper and Nickel) or site I in the N-terminal region that binds Cu(II) and Ni(II) through the donor set NH2, N–, N–, His3-N [104], and the multi-metal binding site (MBS) or site II to which Zn(II) and V(IV)O are bound through His67, Asn99, His247 and Asp249 residues [105,106].
The visible region of the electronic absorption spectra of Cu(II) complexes was studied by time-dependent density functional theory (TD-DFT). The performance of twelve functionals in the prediction of absorption maxima (λ_max) was tested on eleven compounds with different geometry, donors and charge. The ranking of the functionals for λ_max was determined in terms of mean absolute percent deviation (MAPD) and standard deviation (SD) and it is as follows: BHandHLYP > M06 ≫ CAM-B3LYP ≫ MPW1PW91 ~ B1LYP ~ BLYP > HSE06 ~ B3LYP > B3P86 ~ ω-B97x-D ≫ TPSSh ≫ M06-2X (MAPD) and BHandHLYP > M06 ~ HSE06 > ω-B97x-D ~ CAM-B3LYP ~ MPW1PW91 > B1LYP ~ B3LYP > B3P86 > BLYP ≫ TPSSh ≫ M06-2X (SD). With BHandHLYP functional the MAPD is 3.1% and SD is 2.3%, while with M06 the MAPD is 3.7% and SD is 3.7%. The protocol validated in the first step of the study was applied to: i) calculate the number of transitions in the spectra and relate them to the geometry of Cu(II) species; ii) determine the coordination of axial water(s); iii) predict the electronic spectra of the systems where Cu(II) is bound to human serum albumin (HSA) and to the regions 94–97 and 108–112 of prion protein (PrP). The results indicate that the proposed computational protocol allows a successful prediction of the electronic spectra of Cu(II) species and to relate an experimental spectrum to a specific structure.
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Citation Excerpt :
The His residue in the third position is replaced by Tyr in dog serum albumin (DSA, GluAlaTyr) and porcine serum albumin (PSA, AspThrTyr), and Glu in chicken serum albumin (CSA, AspAlaGlu) [132]. HSA plays a major role in the transport of physiological CuII [132], ZnII [133,134] CoII and CaII, and toxic NiII and CdII [135]. Albumins may contain a primary metal binding site, the N-terminal site (NTS or site I) [132], and a secondary site, the multi-metal binding site (MBS or site II) [136].
Vanadium is an element ubiquitously present in our planet's crust and thus there are several organisms that use vanadium for activity or function of proteins. Examples are the vanadium-dependent haloperoxidases and the vanadium-containing nitrogenases. Some organisms that use vanadium have extremely efficient and selective protein-dependent systems for uptake and transport of vanadium and are able to accumulate high levels of vanadium from seawater, vanabins being a unique family of vanadium binding proteins found in ascidians involved in this process. For all of the systems a discussion regarding the role of the V-containing proteins is provided, mostly centered on structural aspects of the vanadium site and, when possible or relevant, relating this to the mechanisms operating. Phosphate is very important in biological systems and is involved in an extensive number of biological recognition and bio-catalytic systems. Vanadate(V) is able to inhibit many of the enzymes involved in these processes, such as ATPases, phosphatases, ribonucleases, phosphodiesterases, phosphoglucomutase and glucose-6-phosphatase, and it appears clear that this is closely related to the analogous physicochemical properties of vanadate and phosphate. The ability of vanadium to interfere with the metabolic processes involving Ca²⁺ and Mg²⁺, connected with its versatility to undergo changes in coordination geometry, allow V to influence the function of a large variety of phosphate-metabolizing enzymes and vanadate(V) salts and compounds have been frequently used either as inhibitors of these enzymes, or as probes to study the mechanisms of their reactions and catalytic cycle. In this review we give an overview of the many examples so far reported, also disclosing that vanadate(IV) may also have an equally efficient inhibiting effect. The prospective application of vanadium compounds as therapeutics has also been an important topic of research. How vanadium may be transported in blood and up-taken by cells are particularly relevant issues, this being mainly dependent on transferrin (and albumin) present in blood plasma. The thousands of studies reported on the effects of vanadium compounds reflect the complexity of the interactions occurring. Although it is not easy to anticipate/determine if a particular effect observed in a test tube or in vitro is also going to take place in vivo, it is clear that vanadium ions may interfere with many metabolic processes at many distinct levels. Emphasis is given on structural and functional aspects of vanadium–protein interactions relevant for vanadium binding and/or for clarification of role of the metal center in the reaction mechanisms. The additional knowledge that the presence of vanadium can change the action of a protein, other than simply inhibiting it, may also be important to understand how vanadium affects biological systems. This possibility, together with the vanadate–phosphate analogy further potentiates the belief that vanadium probably has relevant functions in living beings, which may involve interaction or incorporation of the metal ion and/or its compounds with several proteins.
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IMAC is highly sensitive to the type of solvent [10] and immobilized metal ion used [11,12]. To date, a few human proteins have been identified, some only tentatively, using IMAC and similar approaches [13–19]. The extensive review of that literature is provided in the Section 4 of this paper.
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Citation Excerpt :
Zn(II) is transported and tightly regulated by HSA [10]. A number of studies concluded that the association of Zn(II) and HSA occurred at two inter-domain specific binding sites on HSA secondary structure [11] and Zn(II) can also coordinate with nonspecific binding sites [12]. The Maillard products of a lactose-glycine, in-vitro system, analyzed by atomic absorption spectroscopy revealed that Zn(II) stimulated accumulation of melanoidins at 5 mg/l and suppressed it at the higher concentration of 25 mg/l. [13].
Amino groups of human serum albumin (HSA) can react non-enzymatically with carbonyl groups of reducing sugars to form advanced glycation end products (AGEs). These AGEs contribute to many of the chronic complications of diabetes including atherosclerosis, cataract formation and renal failure. The current study focused on in vitro non-enzymatic reactivity of glyceraldehyde (GA) and methylglyoxal (MG) with HSA and evaluated the rate and extent of AGE formation in the presence of varied concentrations of Zn(II). At normal physiological conditions, GA and MG readily react with HSA. The presence of Zn(II) in HSA–GA or HSA–MG incubation mixtures reduced AGE formation. This finding was confirmed by UV and fluorescence spectrometry, HPLC techniques, and matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF). HPLC studies revealed decreased adduct formation of the glycated protein in the presence of Zn(II). The inhibition of AGE formation was intense at elevated Zn(II) concentrations. The results of this study suggest that Zn(II) may prove to be a potent agent in reducing AGE formation.
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N-ethyl-3-carbazolecarboxaldehyde-3-thiosemicarbazone (ECCT) is proposed as a new sensitive reagent for the extractive spectrophotometric determination of zinc(II). The ECCT forms yellow colored species of zinc(II) at pH range 3.0–5.5 and the complex was extracted into benzene. The Zn(II)–ECCT complex shows maximum absorbance at 420 nm with molar absorptivity and Sandell’s sensitivity being 1.55 × 10⁴ lit mol⁻¹ cm⁻¹ and 4.212 × 10⁻³ μg cm⁻², respectively. The system obeys Beer’s law in the range of 0.4–6.0 mg/l, with an excellent linearity in terms of correlation coefficient value of 0.999. Most of the common metal ions generally found associated with zinc do not interfere. The repeatability of the method was checked by finding relative standard deviation (RSD). The developed method has been successfully employed for the determination of zinc(II) in foods. Various certified reference materials (NIST 1573, NBS 1572 and NIST SRM 8435) have been tested for the determination of zinc for the purpose of validation of the present method.

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A study of zinc distribution in human serum

Abstract

Biochim. Biophys. Acta

Biochemical Med.

Standard Methods in Clinical Chemistry

J. Biol. Chem.

Gastroenterology

Metabolism

Clin. Chim. Acta

Am. J. Clin. Nutr.

Biochemistry

Biochemistry

Scand. J. Clin. Lab. Invest.