Interaction of curium with human serum albumin

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Title: Interaction of curium with human serum albumin
Author: Keskitalo, Markus
Contributor: University of Helsinki, Faculty of Science
Publisher: Helsingin yliopisto
Date: 2019
Language: eng
Thesis level: master's thesis
Discipline: Radiokemia
Abstract: Actinides are heavy elements with no known physiological function in man, animals or plants. The actinides are radioactive without exception. In addition, the actinides exhibit metallotoxic properties. Due to these properties the actinides represent a health hazard to living organisms. This hazard can materialize should actinides be accidentally released into the environment. Decontamination regimes are used to treat humans contaminated with actinides. The knowledge of actinide bioinorganic chemistry inside the tissues and bodily fluids of humans is required for the development of internal decontamination therapies. Unfortunately, fairly little is known of the behaviour of actinides inside the human body at a molecular level. Human serum albumin (HSA) is a blood plasma protein. With a concentration of circa 600 micromolar, it is the most ubiquitous of the blood-borne proteins. HSA has a multitude of physiological functions, one among them being the role of metal carrier. It is tempting to speculate that HSA might be an actor responsible for actinide distribution inside the human body. In this study, the interaction between HSA and trivalent curium was investigated using time-resolved laser fluorescence spectroscopy (TRLFS) in a bid to obtain information useful in decontamination therapy development. TRLFS is a highly sensitive technique that allows the determination of speciation data even at trace level concentrations. Cm(III) has excellent optical properties, making it amenable for study using TRLFS and a convenient representative of trivalent actinides in general. In addition to Cm(III) the trivalent actinide analogue Eu(III), which is also a good fluorescent probe, was also utilized. Nuclear magnetic resonance (NMR) spectroscopy was used in an experiment aimed at resolving the site of interaction. The experiments revealed the existence of a CmHSA complex. It was discovered that 90 % of available Cm(III) was in the CmHSA complex at physiological pH and temperature (7,4 and 310 K, respectively). A pH 8,0 conditional stability constant log K of 6,8 +/- 0,5 and a Cm(III):HSA reaction stoichiometry of 1:1 were determined for the complex. In addition, the thermodynamic parameters deltaH and deltaS were determined. The number of non-water ligands in the first coordination sphere of Cm(III) was determined to be five or six. Furthermore, a combined TRLFS and NMR approach revealed the HSA binding locus of Cm(III) and Eu(III). Based on the results, a model could be presented, in which trivalent actinides bind HSA at the amino-terminus of the protein and that the site shares at least some of its ligands with the canonical Cu(II) binding site of HSA.

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