Copper Transport in Blood
Written By: Paphapin Pairojtanachai
June 13, 2020
Illnesses including Alzheimer’s disease, Parkinson’s disease, and motor neuron disease are linked to the level of copper found in tissues. New studies that investigate the transportation of copper in the bloodstream provide clues about the diagnosis and treatment of these disorders.
Copper is essential for the body’s metabolism: it binds to proteins and acts as enzymes that catalyze various metabolic reactions occurring in the human body. Although this is understood by scientists, the information on the way copper is transported throughout the body or on how homeostasis maintains the amount of copper at a favorable level in certain tissues is not available, says Professor Peep Palumaa, the head of the Research Group of Metalloproteomics at Tallinn University of Technology in Estonia.
Copper is found as footprints over the entire body and is present to a larger extent in tissues or organs, such as the liver, kidneys, brain, heart, and skeletal muscle, where there is high activity. It performs multiple functions, including “producing energy during cell respiration, making red blood cells, mounting immune responses, and maintaining nerve cells.” However, with excessive copper, inflammation and the destruction of free radicals could occur, leading to neurodegenerative diseases. In 2013, a study reported that the buildup of copper in the brain impedes the removal of soluble beta-amyloid molecules and stimulates the clumping together of the molecules to form insoluble plaques. These plaques are a key feature found in patients with Alzheimer’s disease.
To discover more about the failure of the homeostatic regulation of copper, Professor Palumaa and his colleagues worked with three proteins that biochemists deem as important in the process of transporting copper. They developed new innovations called liquid chromatography and inductively coupled plasma mass spectrometry (ICP-MS). These systems work to “separate and identify molecules that are present in trace amounts in a biological fluid, such as blood or cerebrospinal fluid.”
After measuring the affinity of each of the proteins for copper, the researchers found that three-fourths of copper binds to the ceruloplasmin enzyme and one-fourth binds to the albumin enzyme within the bloodstream. Because ceruloplasmin’s affinity for copper is very high, it binds to copper too tightly and is therefore more likely to be assisting another protein that transfers iron. On the other hand, it is more probable that albumin is the “major player” in transporting copper, as its affinity for copper is much lower. In addition to ceruloplasmin and albumin, approximately 0.2% of copper in the blood also binds to an amino acid called histidine. The scientists presume that histidine acts as the catalyst that releases copper from the albumin enzyme. Even though it has been suspected in previous studies that a protein called alpha-2 macroglobulin also transports copper, Professor Palumaa did not find that to a significant amount.
The researchers at Tallinn University of Technology further collaborated with Wilson Therapeutics AB, a Swedish pharmaceutical company. Decuprate, manufactured by the company, is “a promising therapeutic agent to treat Wilson’s disease, a rare genetic disorder that causes copper to accumulate in toxic quantities in the liver, brain, and other tissues.” Decuprate works by attaching itself to copper and provoking the excretion of copper from the body.
With this discovery, it is possible that faulty mechanisms in the metabolism of copper could be detected in order to identify several genetic diseases such as Wilson’s and Menkes disease, as well as Alzheimer’s disease. Professor Palumaa also stated that “In addition to specific diagnoses, the effect of pharmaceuticals normalizing copper metabolism that are used for the treatment of the abovementioned diseases can also be monitored through copper equilibrium in [the] blood.”
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