Re-partitioning of Cu and Zn isotopes by modified protein expression

Copper (Cu) and zinc (Zn) have essential roles in mammalian metabolism: copper in the formation of haemoglobin and red blood cells and Zn and Cu in several enzymes in a number of metabolic pathways. A number of neurodegenerative diseases are associated with abnormalities in the tissue distribution of these trace metals, such as Cu in prion disease [1,2], and Cu and Zn in Alzheimer's disease [3]. Cu has the two isotopes 65Cu and 63Cu, Zn has the five isotopes 64Zn, 66Zn, 67Zn, 68Zn and 70Zn. Different isotopes of the same element have different masses, which leads to different behaviour, and this contribution is concerned with the extent these isotopes are fractionated by small changes in a complex biological system, the brain.Precise analyses of the ratios of transition stable isotopes has only been possible since the development of multi-collector inductively coupled plasma mass spectrometers and associated extraction techniques [4-7]. Variations in the isotopic composition are expressed by delta notation [δ66Zn = (66Zn/64Znsample/66Zn/64Znstandard -1)*1000, and δ65Cu = (65Cu/63Cusample/65Cu/63Custandard -1)*1000 ], which is the deviation of a sample from an international standard in permil (1‰ = 0.1%). Variations in the isotopic composition of trace metals within organisms result from two effects. Biogeochemical processes in the environment lead to different isotopic compositions in, for example, soil, water, and plants. Isotope ratios may therefore be used to trace the origin, or source, of the element in question at the time it enters the body. Secondly, heavy stable isotope ratios fractionate during biochemical processes in organisms, and they are known to fractionate both during the uptake of trace metals into a cell, and as metals pass through membranes within the cell [8,9]. A study of Fe isotopes in human blood samples established that they were fractionated, and that the mean Fe isotope value is different in the blood of men and of women [10]. Such isotope