3. It is observed that this system of faster exchange of zinc arose and is only found in eukaryotes. The ability of zinc in this exchange between a series of sites allows it to integrate such cellular effects which arise from binding to zinc fingers. One case is the binding of hormones, especially sterol hormones. If this central control role of zinc is confirmed it is then possible to consider zinc as a super-hormone or a second messenger [26] and [30]. Note that the tighter binding to many enzymes is

not related to this exchange directly but their synthesis may still depend on chaperones. Deficiency in the zinc proteins in man leads to slow growth and an inability to go through puberty. Both are cured by giving zinc to the patient. This is an example of what Vallee had hoped to find when he first began to examine zinc biochemistry. The final section of my paper refers to a problem Bert and I discussed in more Selleckchem 3 MA social circumstances. We did no experiments and published no papers together in this area. How did zinc biochemistry evolve AC220 cost [29]? It had to be in two steps. First very early zinc enzymes in a low zinc environment with a high binding constant and no exchange and second a later larger amount of zinc in the environment became associated with message functions either of hormones,

in zinc fingers or free zinc acting itself as a messenger in nerve tissue. The earliest use appears to be at the beginning of life around 3.5 Ga whilst the later uses are related to the beginning of single-cell eukaryotes and multi-cell eukaryotes, Fig. 2, Fig. 4 and Fig. 5. One well-recognised pathway of evolution of zinc proteins and of many other proteins is from an original parent by mutation. It is easy to see that mutational changes, in the evolution of somewhat different organisms and within the increasing diversity of recent organisms, will affect the required efficiency of the enzyme. It does not explain the times when evolution of very different proteins occurred, for example the appearance of zinc fingers in unicellular eukaryotes around 2.5 Ga (billion years ago) and more strongly on the

evolution of multicellular eukaryotes Liothyronine Sodium around the time of the Cambrian Explosion, 0.54 Ga, Fig. 4. Both these faster periods of evolution correspond with the periods of faster chemical change in the sea shown by geochemical evidence of both a rapid rise of oxygen in the atmosphere, of sulphate in the sea and of trace elements including zinc in sediments. Both the second two changes arise from oxidation of sulphides. The sediments are assumed to define the probable nature of the sea which would have a great influence on organisms. Using the comparison of the element content of organisms alive today, from the anaerobes to large plants and animals, it is apparent that the content of zinc (or copper) proteins increases in the series of complexity and that the steps of the most rapid changes, Fig.