Fig. 2: Mammalian copper metabolism at the molecular level.

Cu²⁺ is reduced to Cu⁺ with the participation of STEAP, and CTR1 is highly specific for Cu⁺ uptake. Copper-transporting ATPases are located in the TGN, where they pump Cu⁺ from the cytoplasm into the TGN lumen. These copper-transporting ATPases fuse with the plasma membrane to export Cu⁺ when intracellular Cu⁺ increases. Cu⁺ can be sequestered by MT1/2 for storage. Copper is transported by ATP7A through the basolateral membrane of enterocytes into the portal circulation, where it reaches the liver, the primary organ for storing copper. Via ATP7B, extra copper in liver cells is released as vesicles into bile. Cu⁺ is transported by CP to the whole-body system. In addition, Cu⁺ is carried to the nucleus through ATOX1, where it binds to transcription factors to promote the expression of certain genes. To trigger the function of the respiratory chain’s enzymes, COX17 carries Cu⁺ to the SCO1, SCO2, and COX11 which carry copper, and then delivers it to CCO. Cu⁺ can be transferred from CCS to SOD1.