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ABSTRACT
Transition metals such as iron, copper, manganese, and zinc are essential nutrients. The yeast Saccharomyces cerevisiae is an ideal organism for deciphering the mechanism and regulation of metal ion transport. Recent studies of yeast have shown that accumulation of any single metal ion is mediated by two or more substrate-specific transport systems. High-affinity systems are active in metallimited cells, whereas low-affinity systems play the predominant roles when the substrate is more abundant. Metal ion uptake systems of cells are tightly controlled, and both transcriptional and posttranscriptional regulatory mechanisms have been identified. Most importantly, studies of S. cerevisiae have identified a large number of genes that function in metal ion transport and have illuminated the existence and importance of gene families that play related roles in these processes in mammals.
KEY WORDS: uptake, iron, copper, zinc, manganese, regulation, yeast
INTRODUCTION
When medieval cartographers mapped an uncharted region, they would label it "Here there be dragons." Until recently, the field of metal ion transport in eukaryotic organisms was filled with dragons. Thanks to the many researchers studying the baker's yeast Saccharomyces cerevisiae, however, a wealth of new information about metal ion metabolism in all eukaryotes is now available.
Transition metals such as iron, copper, manganese, and zinc are essential nutrients that play critical roles in a variety of biochemical processes. For example, iron and copper readily donate and accept electrons and are important cofactors in electron transport and in many redox-active metalloenzymes. Zinc, which under physiological conditions is not redox active, is a catalytic component of more than 300 enzymes and in many proteins plays critical structural roles. The ability of an organism to accumulate metal ions from its diet is critical to its health. As many as two billion people suffer from malnutrition due to deficiencies of micronutrients such as metal ions. Furthermore, several genetic diseases in humans-including hereditary hemochromatosis, acrodermatitus enteropathica, Wilson disease, and Menkes disease-are caused by mutations that alter metal ion transport.
Despite their nutritional importance, metal ions, when overaccumulated, can have toxic affects. When the intracellular level of a metal ion reaches an excess, the metal can inhibit critical processes, for example by competing with other metal ions for enzyme-active sites and other important biological ligands. Excess...