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requirement. This state of affairs is attributable to a number of factors, including the homeostatic processes that maintain zinc occupancy of the catalytic sites of these enzymes and the lack of consistency in findings between studies. Other factors include a lack of sensitivity, the inaccessibility of optimal tissues to assay, or, simply, inadequate research. The lack of baseline dietary data also negates the potential value of some reports. Given these limitations, limited dose-response data, and inconsistent responses to dietary zinc (Bales et al., 1994; Davis et al., 2000; Paik et al., 1999; Ruz et al., 1992; Samman et al., 1996), the activities of zinc-dependent enzymes, including alkaline phosphatase, copper-zinc superoxide dismutase, and lymphocyte 5′-nucleotidase, can at most serve as supportive indicators of dietary zinc requirements at this time. Although it is not consistently responsive to zinc intake, the activity of plasma 5′-nucleotidase (Beck et al., 1997a), which is derived from the CD73 cell surface markers of B and T cells, merits specific recognition as a potential marker of zinc status (Failla, 1999).

Metallothionein and Zinc-Regulated Gene Markers

Erythrocyte metallothionein concentrations have been reported to be responsive to both increased and restricted dietary zinc (Grider et al., 1990; Thomas et al., 1992), but the sensitivity and precision of this index has not been thoroughly evaluated. Monocyte metallothionein messenger RNA responds rapidly to in vivo zinc supplementation (Sullivan et al., 1998) and merits additional research. Moreover, this approach points the way for future exploration of molecular markers of zinc status including, for example, a whole family of zinc transporters that are now being identified (Failla, 1999; McMahon and Cousins, 1998).

Indexes of Immune Status

Zinc is essential for the integrity of the immune system, and inadequate zinc intake has many adverse effects (Shankar and Prasad, 1998). Though the immune system, which is thought to underlie several of the most important sequelae of mild zinc deficiency, is sensitive to even mild zinc deficiency, the effects on functional indexes of zinc status are not specific. At this time, therefore, changes in indexes of immune status with manipulation of dietary zinc can serve only as a limited indicator for dietary zinc requirements.

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