Nearly 100 specific enzymes (e.g., EC 126.96.36.199 alcohol dehydrogenase) depend on zinc for catalytic activity. Zinc removal results in loss of activity, and reconstitution of the holoenzyme with zinc usually restores activity. Examples of zinc metalloenzymes can be found in all six enzyme classes (Vallee and Galdes, 1984). Well-studied zinc metalloenzymes include the ribonucleic acid (RNA) polymerases, alcohol dehydrogenase, carbonic anhydrase, and alkaline phosphatase. Zinc is defined as a Lewis acid, and its action as an electron acceptor contributes to its catalytic activity in many of these enzymes. Changes in activity of zinc metalloenzymes during dietary zinc restriction or excess have not been consistent in experimental studies with humans or animals.
The structural role of zinc involves proteins that form domains capable of zinc coordination, which facilitates protein folding to produce biologically active molecules. The vast majority of such proteins form a “zinc finger-like” structure created by chelation centers, including cysteine and histidine residues (Klug and Schwabe, 1995). Some of these proteins have roles in gene regulation as dioxyribonucleic acid binding transcription factors. Examples include nonspecific factors such as Sp1 and specific factors such as retinoic acid receptors and vitamin D receptors. These structural motifs are found throughout biology and include the zinc-containing nucleocapside proteins of viruses such as the human immunodeficiency virus (Berg and Shi, 1996). The relationship of zinc finger protein bioactivity to zinc in the diet has not received extensive study. Zinc also provides a structural function for some enzymes; copper-zinc superoxide dismutase is the most notable example. In this instance, copper provides catalytic activity, whereas zinc’s role is structural. Also of potential relevance as a structural role is the essentiality of zinc for intracellular binding of tyrosine kinase to T-cell receptors, CD4 and CD8α, which are required for T-lymphocyte development and activation (Huse et al., 1998; Lin et al., 1998).
The role of zinc as a regulator of gene expression has received less attention than its other functions. Metallothionein expression is regulated by a mechanism that involves zinc’s binding to the transcription factor, metal response element transcription factor (MTF1), which activates gene transcription (Cousins, 1994; Dalton et al., 1997). The number of genes that are activated by this type of mechanism is not known, however, because a null mutation for MTF1 is lethal during fetal development of mice, suggesting some critical genes must be regulated by MTF1 (Günes et al., 1998). Zinc transporter proteins associated with cellular zinc accumulation and release may be among the metal response element-regulated family