Abstract
The binding of Al3+ by human serum transferrin has been investigated by u.v.-visible difference spectroscopy. In the presence of 25 mM-HCO3- at pH 7.4, the apparent association constants were found to be 1.69 x 10(12) M-1 and 5.36 x 10(11) M-1. These association constants are pH-dependent, reducing with both increasing and decreasing pH. The apparent pKa values were found to be 6.7 and 8.2. Competitive assays of binding of Al3+ to transferrin in the presence of citrate and human serum albumin at molar ratios corresponding to those found in normal plasma showed that a considerable amount of Al3+ was not bound to transferrin. Taking a concentration of 5 microM as a typical value observed for the plasma of patients on haemodialysis [Harris & Sheldon (1990) Inorg. Chem. 29, 119-124] the competitive binding assay indicate that approximately 60% of it is bound to transferrin, approximately 34% to albumin and the remainder to citrate. These results therefore suggest that, although transferrin at pH 7.4 is the major Al(3+)-binding component of plasma, an appreciable amount of Al3+ present in patients on haemodialysis may be bound to albumin.
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Selected References
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- Aisen P., Leibman A., Zweier J. Stoichiometric and site characteristics of the binding of iron to human transferrin. J Biol Chem. 1978 Mar 25;253(6):1930–1937. [PubMed] [Google Scholar]
- Aisen P., Listowsky I. Iron transport and storage proteins. Annu Rev Biochem. 1980;49:357–393. doi: 10.1146/annurev.bi.49.070180.002041. [DOI] [PubMed] [Google Scholar]
- Anderson B. F., Baker H. M., Dodson E. J., Norris G. E., Rumball S. V., Waters J. M., Baker E. N. Structure of human lactoferrin at 3.2-A resolution. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1769–1773. doi: 10.1073/pnas.84.7.1769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bailey S., Evans R. W., Garratt R. C., Gorinsky B., Hasnain S., Horsburgh C., Jhoti H., Lindley P. F., Mydin A., Sarra R. Molecular structure of serum transferrin at 3.3-A resolution. Biochemistry. 1988 Jul 26;27(15):5804–5812. doi: 10.1021/bi00415a061. [DOI] [PubMed] [Google Scholar]
- Bertholf R. L., Wills M. R., Savory J. Quantitative study of aluminum binding to human serum albumin and transferrin by a chelex competitive binding assay. Biochem Biophys Res Commun. 1984 Dec 28;125(3):1020–1024. doi: 10.1016/0006-291x(84)91385-8. [DOI] [PubMed] [Google Scholar]
- Cochran M., Coates J., Neoh S. The competitive equilibrium between aluminium and ferric ions for the binding sites of transferrin. FEBS Lett. 1984 Oct 15;176(1):129–132. doi: 10.1016/0014-5793(84)80926-6. [DOI] [PubMed] [Google Scholar]
- Cochran M., Cochran M., Coates J. H., Kurucsev T. Direct spectrophotometric determination of the two site binding of aluminum to transferrin. Life Sci. 1987 Jun 15;40(24):2337–2341. doi: 10.1016/0024-3205(87)90507-8. [DOI] [PubMed] [Google Scholar]
- Farrar G., Altmann P., Welch S., Wychrij O., Ghose B., Lejeune J., Corbett J., Prasher V., Blair J. A. Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain. Lancet. 1990 Mar 31;335(8692):747–750. doi: 10.1016/0140-6736(90)90868-6. [DOI] [PubMed] [Google Scholar]
- Ganrot P. O. Metabolism and possible health effects of aluminum. Environ Health Perspect. 1986 Mar;65:363–441. doi: 10.1289/ehp.8665363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris W. R., Pecoraro V. L. Thermodynamic binding constants for gallium transferrin. Biochemistry. 1983 Jan 18;22(2):292–299. doi: 10.1021/bi00271a010. [DOI] [PubMed] [Google Scholar]
- King S. W., Savory J., Wills M. R. Aluminum distribution in serum following hemodialysis. Ann Clin Lab Sci. 1982 Mar-Apr;12(2):143–149. [PubMed] [Google Scholar]
- King S. W., Wills M. R., Savory J. Serum binding of aluminum. Res Commun Chem Pathol Pharmacol. 1979 Oct;26(1):161–169. [PubMed] [Google Scholar]
- Lestas A. N. The effect of pH upon human transferrin: selective labelling of the two iron-binding sites. Br J Haematol. 1976 Mar;32(3):341–350. doi: 10.1111/j.1365-2141.1976.tb00937.x. [DOI] [PubMed] [Google Scholar]
- Martin R. B. Citrate binding of Al3+ and Fe3+. J Inorg Biochem. 1986 Oct-Nov;28(2-3):181–187. doi: 10.1016/0162-0134(86)80081-2. [DOI] [PubMed] [Google Scholar]
- Martin R. B., Savory J., Brown S., Bertholf R. L., Wills M. R. Transferrin binding of Al3+ and Fe3+. Clin Chem. 1987 Mar;33(3):405–407. [PubMed] [Google Scholar]
- Peters T., Jr Serum albumin. Adv Protein Chem. 1985;37:161–245. doi: 10.1016/s0065-3233(08)60065-0. [DOI] [PubMed] [Google Scholar]
- Rahman H., Skillen A. W., Ward M. K., Channon S. M., Kerr D. N. Affinity of the aluminium binding protein. Int J Artif Organs. 1986 Mar;9(2):93–96. [PubMed] [Google Scholar]
- Trapp G. A. Plasma aluminum is bound to transferrin. Life Sci. 1983 Jul 25;33(4):311–316. doi: 10.1016/s0024-3205(83)80002-2. [DOI] [PubMed] [Google Scholar]