Molecular biological approaches to studying trace minerals: why should clinicians care?

The approaches and tools of molecular biology have been enormously valuable to all branches of biological science over the last decade. Nutrition is no exception, where studies on the influence of nutrients on gene expression and of gene products on nutrient metabolism have resulted in a much more sophisticated and detailed understanding of nutritional biochemistry. An example of this as applied to trace minerals research can be seen in the area of thyroidology. Until recently, the sole link between thyroid hormones and trace minerals was iodide. Then the thyroid hormone receptor was cloned and analysis of the protein coding sequence showed it to be a member of a large family of gene activating receptor proteins. These all possess a region containing two clusters of cysteine residues, thought to chelate zinc, which is required for binding of the receptors to their target genes. Zinc appears to be necessary for the biological functioning of not only the thyroid hormone receptor but also many other nuclear proteins which regulate gene expression. The principal product of the thyroid gland is thyroxine from which the more active form of the hormone, triiodothyronine, is derived by peripheral monodeiodination. One of the two enzymes responsible, type I 5'-iodothyronine deiodinase, was recently cloned and shown to contain selenocysteine. Thus production of the active thyroid hormone is dependent on selenium status. These advances made with molecular biology have important implications for clinicians. The possibilities for understanding the clinical picture are immediately enhanced, improving both diagnosis and treatment. Molecular biology also provides the opportunity for developing more specific and sensitive tools for assessing nutritional status. Diseases with a genetic basis can be unequivocally diagnosed and perhaps even treated. A strength of nutrition is that it encompasses molecular biology and clinical practice and practitioners of each can benefit from an understanding of the complementary area.