As children some of us may remember these huge copper pans which hung over the stove, showing off a distinctive green patina that, we were told, was poisonous. And yet the jam we spread on our bread was made in them. Indeed, copper is essential to life. Without traces of this heavy metal in our system, a lot can go wrong because many enzymes depend on it. However, the level of copper inside us must be constantly checked. This is carried out by transmembrane pumps which taxi copper in and out of cells. One such copper pump is known as the Menkes disease-associated protein – simply because John Menkes, an American neurologist, was the first to describe the illness.
The importance of copper in our system was first brought to light when – in the 1930s – an Australian vet observed poor neurodevelopment in the lambs of sheep that had grazed in copper-deficient pastures during their pregnancy. The lambs’ wool was also unusually brittle. In the 1970s, David Danks, a British pediatrician, described the same kind of phenotype in infants who presented a neurological disease and associated his findings with those made on the Australian lambs. In between times, John Menkes had meticulously described an inherited X-linked disease in the male infants of one family where what he depicted as ‘kinky hair’ was one of the distinctive features. It was only in the 1990s however, that the gene was tracked down and the protein’s sequence unveiled.
Menkes protein is a copper-transporting enzyme which shuttles copper across plasma membranes, thus keeping a close eye on copper levels in the cell’s cytosol. The pump is found in most tissues and, besides supervising copper trafficking within cells, it also ships copper from the gastrointestinal tract into the bloodstream, and from there into the brain. A deficiency in Menkes protein hinders copper transport. As a consequence, a whole battery of copper-dependent enzymes are affected bringing about many different kinds of symptoms, amongst which severe neurological disorders. It’s the bitter side of Granny’s jam.