Svetlana Lutsenko of Physiology on the importance of copper metabolism:
People don’t usually think of copper as a nutrient to include in their diet. Does copper play a big role in the body?
LUTSENKO: The vital importance of trace elements is often underappreciated. Copper is needed for many reactions in the body: respiration, hair and skin coloring, neurotransmitter formation, iron metabolism and blood vessel formation.
Should people be worried about getting enough copper in their diet?
LUTSENKO: There is good news for both health conscious and undisciplined individuals, because there is a lot of copper in spinach and grain, but there is also copper in chocolate and nuts. One can develop a copper deficiency, but it is not likely get too much copper through the diet.
Is there ever a case when healthy is too healthy?
LUTSENKO: I was talking to a doctor who had a patient come in with neurological symptoms--problems walking and keeping balance-- and over time she deteriorated. They didn’t figure out what was going on until they did very extensive blood work. They found out she was copper-deficient, but all the genetic tests for copper diseases came out normal. It turns out that this person was a fan of supplements. She would go to Costco and get the big bottle of zinc and she would eat 400 mg of zinc every day, which is a lot. When one consumes a lot of zinc, the body responds by producing specific proteins which bind zinc, but this protein bound copper too. She ate too much zinc, depleted her body of copper and developed copper deficiency.
Ok, no excessive zinc supplements. Check. Are there other causes of copper deficiency?
LUTSENKO: Well, there have been potential problems identified with patients that have bariatric surgery, which is a way to treat morbidly obese patients. In bariatric surgery, a part of the stomach and a piece of the intestine is removed and it just happens to be the piece where most of the copper is absorbed. If these patients are not monitored closely and if one doesn’t supply a necessary amount of copper in the body, these patients 2 or 3 years down the road can start developing neurological symptoms because of copper deficiency.
How did you get interested in copper metabolism?
LUTSENKO: I became interested in this about 15 years ago when the first copper transport genes were discovered. I was working on sodium and calcium transport in mammals. A colleague and former classmate was sequencing the human genome, specifically chromosome 13 at the Wilson’s disease gene locus. He called me up and said he was getting pieces that looked like one of the transporters I was working with and he wanted to know if I’d like to take a look at it. I was very excited because it was new and it was related to human disease.
What specific aspects of copper metabolism does your lab study?
LUTSENKO: We are interested in how copper gets in cells, how it’s distributed and how excess is removed out of the cell. In the body, copper ions do not float freely, like sodium or potassium. Copper is always carried by proteins. It gets into the cell through special protein transporters and once it’s in the cell, it’s immediately bound by proteins called copper chaperones. These chaperones make sure that copper behaves, so it’s not reacting with oxygen making reactive oxygen that bombards and damages the cell. The chaperones deliver copper to the right destinations in the cell. Another class of transporters export copper and deliver it to other cells. Several genetic diseases like Menkes and Wilson’s disease result from problems with copper transporters. We study Wilson’s disease in a mouse model.
Lutsenko on the importance of copper metabolism:
"Copper plays a very important role in human health and it’s very essential for human metabolism. Yet, it’s important to have proper copper balance. So, if there’s insufficient amount of copper as it happens in the case of Menkes disease, these patients develop neurological problems. They also have heart problems and problems with blood vessel formation. And, this is because copper is required as a co-factor of enzymes which participate in respiration, information of neurotransmitters and neuro-hormones and also enzymes which participate in protection of cells against oxidative stress.
If copper is too high in the cells, it’s also a problem. And, this is an example of Wilson’s disease, where patients cannot export excessive copper out of the liver and the brain and copper accumulates to a very high level. And, these patients have problems with liver function, and also neurological and psychiatric problems.
So, to understand how copper is distributed within the human body, we use different methodologies. So, we use protein chemistry where we’re trying to express proteins which participate in copper metabolism, understand the function, understand the structure and understand what happens with the functions of these proteins when there are mutations--similar to mutations that happen in human patients. In addition, we’re interested in understanding how these transporters are regulated within in a cell. And, for this study we’re using cellular biology approaches.
And, this is important to understand because regulation of copper transporters and copper metabolism may play a very important role in cancer. It turns out that copper misbalance affects treatment of patients and treatment of cells during cancer with a drug called cisplatin. If there are changes in copper metabolism, it may alter resistance of cells to this chemotherapeutic drug.
And, lastly we are developing animal models to try to understand better the course of the disease and how disease progresses and how disease develops and whether or not we can pinpoint more closely different stages of disease by better characterizing important biochemical markers. And, also find tools to treat the disease of both copper deficiency and copper accumulation better."