Vanadium and copper in clinical solutions of albumin and their potential to damage protein structure

Authors

  • G. J. Quinlan,

    1. Divisions of Chemistry and Haematology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, U.K.
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  • C. Coudray,

    1. Laboratoire de Biochimie C, Hôpital A. Michallon, 38700 La Tronche, France
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  • A. Hubbard,

    1. Divisions of Chemistry and Haematology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, U.K.
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  • J. M. C. Gutteridge

    Corresponding author
    1. Oxygen Chemistry Laboratory, Department of Anaesthesia and Intensive Care, Royal Brompton Hospital and National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, U.K.
    • Oxygen Chemistry Laboratory, Department of Anaesthesia and Intensive Care, Royal Brompton Hospital and National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, U.K
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Abstract

Solutions of albumin, for injectable use in humans, are shown to contain the transition metals vanadium, copper, and iron. Variation in the concentration of these metal ions among products from six different manufacturers suggests that problems of metal contamination arise through manufacturing processes. Vanadium concentrations correlated with the loss of tryptophan residues in albumin, whereas copper concentrations correlated with loss of thiol groups and tryptophan residues. Incubation of vanadate and cupric salts with the thiol group-containing molecules cysteine and glutathione resulted in reduction of the metal ions to lower oxidation states. Reduced forms of vanadium and copper were able to transfer electrons to molecular oxygen and produce highly reactive and damaging intermediates of oxygen, such as the hydroxyl radical.

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