51³Ô¹ÏÍø

High precision isotope measurements reveal poor control of copper metabolism in parkinsonism

‘High precision isotope measurements reveal poor control of copper metabolism in parkinsonism’

Larner F, Sampson B, Rehkämper M, Weiss DJ,   Dainty JR, O’Riordan S, Panetta T, Bain PG

Metallomics 2013  DOI: 10.1039/c3mt20238k

Following a grant from Parkinson’s UK (PI: ), Dr Larner and colleagues from the Departments of Earth Sciences, Mineralogy, Clinical Biochemistry and the Division of Brain Sciences at 51³Ô¹ÏÍø and the Institute of Food Research in Norwich devised a new way of measuring the ratio of the non-radioactive copper isotopes ⁶⁵Cu/⁶³Cu accurately.

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine.

Consequently, this methodology was used to examine human Cu metabolism in ten Parkinsonism patients and ten healthy control subjects. The analyses of blood serum ⁶⁵Cu/⁶³Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism.

Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques.

This pilot investigation supports full-scale medical studies into the Cu metabolism of patients with Parkinsonism. The methodology can also be applied to other conditions in which disordered metabolism is suspected, for example Wilson’s disease.