Transporters in the absorption and utilization of zinc and copper.

ABSTRACT

Before the discovery and elucidation of transporters, mammals were thought to cotransport Cu or Zn as an anionic complex, such as binding with an AA as a chelate or a receptor such as transferrin. In 1995, the first mammalian Zn transporter (ZnT) gene, ZnT1, was identified. However, 2 protein families are now thought to be involved in Zn transport. The ZnT family reduces intracellular Zn by aiding in efflux from the cell or promoting the influx into intracellular vesicles. The mechanism of ZnT transport against a Zn concentration gradient is unknown; however, only ZnT1 appears to be located at the plasma membrane. It has been shown to respond in tissues in a variety of ways to Zn reduction and supplementation. In our laboratory, we have found ZnT1 and metallothionein to work in concert during pharmacological Zn supplementation. The second protein family, Zip proteins, provides Zn transport from extracellular fluid or intracellular vesicles into the cytoplasm and has not been identified in a livestock species. Like Zn, no good indicator of status has been identified for Cu. However, the recent identification of Cu transporters and chaperones gives researchers the opportunity to understand the regulation of Cu trafficking where the proteins are modified by posttranslational mechanisms. Two Cu transporters, Ctr1 and Ctr3, mediate high-affinity Cu uptake. A small cytoplasmic protein, MURR1, has been identified in human hepatic tissue, but its role in Cu metabolism is unknown. The discovery of Cu chaperones that are involved in facilitating Cu absorption into proteins may provide an excellent status indicator. It has been shown that the Cu chaperone for Cu/Zn superoxide dismutase (CCS) is increased in tissue of Cu-deficient rats, induced when moderately high Zn diets are fed. We have recently found CCS in the young pig. Other Cu chaperone proteins that have been identified are COX17 and Atox1. As with CCS, they are involved in making Cu available to apo-enzymes inside the cell. It is essential that these new molecular findings be used to evaluate the bioavailability of and nutritional need for Cu and Zn in livestock.