Binding of zinc to alpha-2-macroglobulin and its role in enzyme binding activity

Adham, Nabeel F.; Song, Min-Ae; Rinderknecht, H.

doi:10.1016/0005-2795(77)90378-6

Cited by 31 publications

(11 citation statements)

References 18 publications

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“…The approach taken was to obtain Nterminal and internal amino acid sequence to be used in reverse transcription-polymerase chain reaction (RT-PCR) cloning and screening. As will be shown, the large bsubunitQ of transcuprein was identified as a member of the macroglobulin family, one form of which is already recognized as a carrier of the metal ion zinc [25]. The small bsubunitQ was due to albumin contamination.…”

Section: Introductionmentioning

confidence: 92%

Transcuprein is a macroglobulin regulated by copper and iron availability

Liu¹,

Lo²,

Askary³

et al. 2007

The Journal of Nutritional Biochemistry

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Transcuprein is a high-affinity copper carrier in the plasma that is involved in the initial distribution of copper entering the blood from the digestive tract. To identify and obtain cDNA for this protein, it was purified from rat plasma by size exclusion and copper-chelate affinity chromatography, and amino acid sequences were obtained. These revealed a 190-kDa glycosylated protein identified as the macroglobulin alpha(1)-inhibitor III, the main macroglobulin of rodent blood plasma. Albumin (65 kDa) copurified in variable amounts and was concluded to be a contaminant (although it can transiently bind the macroglobulin). The main macroglobulin in human blood plasma (alpha(2)-macroglobulin), which is homologous to alpha(1)-inhibitor III, also bound copper tightly. Expression of alpha(1)I3 (transcuprein) mRNA by the liver was examined in rats with and without copper deficiency, using quantitative polymerase chain reaction methodology and Northern blot analysis. Protein expression was examined by Western blotting. Deficient rats with 40% less ceruloplasmin oxidase activity and liver copper concentrations expressed about twice as much alpha(1)I3 mRNA, but circulating levels of transcuprein did not differ. Iron deficiency, which increased liver copper concentrations by threefold, reduced transcuprein mRNA expression and circulating levels of transcuprein relative to what occurred in rats with normal or excess iron. We conclude that transcupreins are specific macroglobulins that not only carry zinc but also carry transport copper in the blood, and that their expression can be modulated by copper and iron availability.

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Section: Introductionmentioning

confidence: 92%

Transcuprein is a macroglobulin regulated by copper and iron availability

Liu¹,

Lo²,

Askary³

et al. 2007

The Journal of Nutritional Biochemistry

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“…The binding site is situated at the interface of domains I and II, which consists of two Hisnitrogen atoms (His-67, His-247), two carboxylate-oxygen donor atoms (Asn-99, Asp-249) and a water molecule in the coordination sphere, and the Zn center adopts a distorted trigonal bipyramidal geometry [26,34]. a2M is a fairly large protein with 720 kDa, but found at much lower concentration in the blood than albumin (2-6 mM), and with conditional formation constants of logK 1 ' 5 7.49 and logK 2 ' 5 5.12 it has also considerable Zn(II)-binding properties [29,[35][36][37]. Another possible Zn(II) binder is the 79 kDa iron transport protein Tf (37 mM in serum), but 30% of the binding sites are occupied by Fe(III) ions in the serum [27,33].…”

Section: Resultsmentioning

confidence: 99%

“…[16,17,[26][27][28][29] at physiological pH and at 251C in the presence of HCO 3 À . The other LMM components of the serum were omitted from the modeling calculations because of their negligible Zn(II)-binding abilities [30].…”

Section: Data Processing and Calculationsmentioning

confidence: 99%

“…This result might be explained by the low concentration of Tf in serum and also the iron-binding sites of transferrin are partly occupied by Fe(III), competing for the same binding site as Zn(II) [27]. [16,17,[26][27][28][29]. The modeling calculations for the Zn(II) distribution in artificial serum and with the most important HMM and LMM components (HSA, Tf, Cys, His, cit) showed that most of the Zn(II) is bound to the HMM fraction, mostly to HSA (Fig.…”

Section: Interaction With Proteins In Human Serummentioning

confidence: 99%

See 1 more Smart Citation

Biodistribution of anti‐diabetic Zn(II) complexes in human serum and in vitro protein‐binding studies by means of CZE–ICP‐MS

et al. 2009

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Application of modern analytical technology for studying the fate of metallodrugs after administration to the blood is of utmost importance for drug development. Zn(II) compounds are under development as insulin-enhancing drugs with potential use in the treatment of diabetes. In comparison to the well-established vanadium compounds, especially the lower risk of adverse effects due to the essentiality of the element in biological processes is advantageous. Herein, CZE-ICP-MS studies on the interaction of Zn(II)-maltolato, -2-picolinato and -2,6-dipicolinato complexes with human serum proteins are discussed and modeling calculations were confirmed by experimental results. Studies with human serum reveal preference for HSA over other less abundant proteins and serum components.

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“…2M also has considerable Zn(II) binding properties, but it is present at a much lower concentration in the blood serum than albumin (2-6 M), with conditional formation constants of log K 1 = 7.49 and log K 2 = 5.12 [168][169][170][171]. The third possible Zn(II) binder is Tf, where the Zn(II) binding constants are log K 1 = 7.8 and log K 2 = 6.4 (15 mM NaHCO 3 ) [172,173] If both the HMM and the LMM serum binders are considered together, then modeling calculations indicate that most of the total serum Zn(II) is bound to the serum proteins (~98%), where HSA is the primary binder (80-90%) [29,34,169,173] followed by 2M (5-15%) [169][170][171].…”

Section: Speciation Of Zn(ii) In Blood Serummentioning

confidence: 99%