The extent of digestion of the complete diet is a major determinant of how well trace metal (elements) are absorbed by the gastrointestinal tract. Malabsorption tends to reduce trace metal uptake and absorption. Copper must be reduced to the cuprous ion (Cu+) prior to uptake mediated by the apically located CRT1 transporter. CRT1-mediated transport increases in dietary copper deficiency. Cu+ is transported across the trans-Golgi network by ATP7A. This transporter is also located at the basolateral membrane where an ATP-requiring mechanism pumps Cu+ into the plasma. ZIP4 is the major zinc transporter located at the apical membrane. Zip4 gene transcription increases in zinc deficiency and contributes to homeostatic upregulation of zinc transport at the apical surface. Zn2+ is transported into the trans-Golgi network by the transporter ZnT7 and/or could be bound to cytoplasmic binding proteins such as metallothionein. This protein acts as a metal buffer and the metallothionein gene is regulated by copper and zinc. Elevated synthesis of the protein may scavenge copper ions and limit copper availability for transport by ATP7A. Zinc associated with vesicles is transported from enterocytes by ZnT1 and perhaps other efflux transporters. Zinc transporter ZIP14 is believed to contribute to intestinal barrier function. Other ZIP and ZnT proteins may contribute to trafficking of zinc and other trace metals by enterocytes. Manganese absorption does not appear to require the metal transporter DMT1. Both hepatic ZIP14 and ZnT10 are necessary for effective secretion of manganese into the bile to prevent manganese accumulation by tissues. Selenocysteine and selenomethionine are well-absorbed sources of selenium and absorption occurs via various amino acid transporters, but without homeostatic regulation. Dietary deficiency of each of these trace metals has been shown to produce deficiency signs in humans and rodents. Defects in transport of zinc, copper, and manganese have been linked to specific medical disorders.
