or increased unless these changes in intake are severe and prolonged (Cousins, 1989a). Preliminary kinetic data indicate that the combined size of readily exchangeable zinc pools (i.e., those that exchange with zinc in plasma within 72 hours) decreases with dietary zinc restriction (Miller et al., 1994). Fasting results in increased plasma zinc concentration, an outcome that possibly reflects catabolic changes in muscle protein. Cyclic postprandial changes in plasma zinc concentration have been documented (King et al., 1994). In both cases, hormonally regulated events are the biochemical basis for the changes. Albumin is the principal zinc-binding protein in plasma from which most metabolic zinc flux occurs. Functional aspects of zinc tightly bound to α-2-macroglobulin have not been described. Plasma amino acids bind some zinc and could be an important source of zinc excretion.
Zinc secretion into and excretion from the intestine provides the major route of endogenous zinc excretion. It is derived partially from pancreatic secretions, which are stimulated after a meal. Biliary secretion of zinc is limited, but intestinal cell secretions also contribute to fecal loss (Lonnerdal, 1989). These losses may range from less than 1 mg/day with a zinc-poor diet to greater than 5 mg/day with a zinc-rich diet, a difference that reflects the regulatory role that the intestinal tract serves in zinc homeostasis. Urinary zinc losses are only a fraction (less than 10 percent) of normal fecal losses (King and Keen, 1999). Zinc transporter activity may account for renal zinc reabsorption (McMahon and Cousins, 1998), and glucagon may help regulate it. Increases in urinary losses are concomitant with increases in muscle protein catabolism due to starvation or trauma. The increase in plasma amino acids, which constitute a potentially filterable zinc pool, is at least partially responsible. Zinc loss from the body is also attributed to epithelial cell desquamation, sweat, semen, hair, and the menstrual cycle.
Individuals with malabsorption syndromes including sprue, Crohn’s disease, and short bowel syndrome are at risk of zinc deficiency due to malabsorption of zinc and increased urinary zinc losses (Pironi et al., 1987; Valberg et al., 1986). In mild human zinc deficiency states, the detectable features and laboratory/functional abnormalities of mild zinc deficiency are diverse. This diversity is not altogether surprising in view of the biochemistry of zinc and the ubiquity of this metal in biology with its participation in an extra-ordinarily wide range of vital metabolic processes. Impaired growth