Fig. 1: Copper metabolism in mammals at a molecular level.

Cu⁺ can be sequestered by MT for storage. CTR1 is highly specific for the uptake of Cu⁺. At physiologic Cu⁺ levels, copper-transporting ATPases localize in the TGN, where they pump Cu⁺ from the cytoplasm into the lumen of the TGN. When intracellular Cu⁺ increases, these copper-transporting ATPases fuse with the plasma membrane to export Cu⁺. In the basolateral membrane of enterocytes, copper is pumped by ATP7A into the portal circulation and enters the main organ of copper storage, the liver. Excess copper in liver cells is secreted into bile in the form of vesicles via ATP7B. Cu⁺ travels through the copper transport ATP7B-TGN pathway to form CP, which is then transported to various systems throughout the body. In addition, ATOX1 transports Cu⁺ to the nucleus, where it binds to transcription factors and drives gene expression. COX17 transports Cu⁺ to the copper-carrying proteins SCO1, SCO2, and COX11 and delivers it to CCO to activate the activity of enzymes in the respiratory chain. CCS can transfer Cu⁺ to SOD1. ATOX1 antioxidant-1, ATP7A copper-transporting ATPase alpha, ATP7B copper-transporting ATPase beta, CCO cytochrome C oxidase, CTR1 copper transporter 1 of CCO, CCS Cu chaperone for SOD1, COX11 cytochrome c oxidase copper chaperone 11, COX17 cytochrome C oxidase copper chaperone 17, CP ceruloplasmin, GSH glutathione, MT metallothionein, SCO1 synthesis of cytochrome C oxidase 1, SCO2 synthesis of cytochrome C oxidase 2, SOD1 superoxide dismutase 1, TGN trans Golgi network. The figure was created with Figdraw (https://www.figdraw.com/).