Copper is an essential trace element that the diet supplies well above daily need, yet free copper inside cells is kept very low, because unbound copper is toxic. The body therefore invests in proteins that carry copper, hand it to the enzymes that need it, and store the excess until it can be excreted.
How copper moves through the body
The copper absorbed in the intestine is transported in the blood to different organs through the loose attachment it has with albumin. Most of the absorbed copper is transported to the liver through the portal vein.
Inside the cells, copper is barely free: it is mostly attached to the enzymes that use it, or carried between different cell compartments with the help of intracellular proteins such as metallochaperones, which deliver copper to its targets without letting it react with other molecules. In the liver, copper is attached to ceruloplasmin, the main copper-carrying protein of the blood. Ceruloplasmin circulating in the serum in adult life is about 200–400 mg/L. Ceruloplasmin is an inflammatory reactant, so it increases during inflammatory conditions, infections, pregnancy and the use of exogenous estrogen.
In plasma, ceruloplasmin carries about 90% of the copper, and the remainder is bound to albumin and other proteins. The small non-ceruloplasmin-bound fraction, often called free copper, is the reactive part, and it is the fraction the kidney filters and the fraction the tests for Wilson disease follow.
When intestinal and liver cells are overloaded with copper, metallothionein is induced; these are intracellular proteins that bind copper in a non-toxic form and hold it until the cell can deal with it.
The enzymes that need copper
Copper is a cofactor for enzymes across several systems, which is why both its deficiency and its overload cause disease. Lysyl oxidase cross-links collagen and elastin, so copper is needed for connective tissue. Superoxide dismutase is a free radical scavenger, and cytochrome oxidase, which is Complex IV of the mitochondrial electron transport chain, carries electrons to oxygen, so copper sits at the centre of energy metabolism. Tyrosinase produces pigment, and dopamine monooxygenase is needed for neurotransmission.