The molecular mechanisms of copper metabolism and its roles in human diseases
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MOLECULAR AND CELLULAR MECHANISMS OF DISEASE
The molecular mechanisms of copper metabolism and its roles in human diseases Ji Chen 1,2 & Yunhui Jiang 3 & Hua Shi 4 & Yougong Peng 5 & Xueying Fan 1 & Chenghua Li 1 Received: 15 February 2020 / Revised: 13 May 2020 / Accepted: 29 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Copper is an essential element in cells; it can act as either a recipient or a donor of electrons, participating in various reactions. However, an excess of copper ions in cells is detrimental as these copper ions can generate free radicals and increase oxidative stress. In multicellular organisms, copper metabolism involves uptake, distribution, sequestration, and excretion, at both the cellular and systemic levels. Mammalian enterocytes take in bioavailable copper ions from the diet in a Ctr1-dependent manner. After incorporation, cuprous ions are delivered to ATP7A, which pumps Cu+ from enterocytes into the blood. Copper ions arrive at the liver through the portal vein and are incorporated into hepatocytes by Ctr1. Then, Cu+ can be secreted into the bile or the blood via the Atox1/ATP7B/ceruloplasmin route. In the bloodstream, this micronutrient can reach peripheral tissues and is again incorporated by Ctr1. In peripheral tissue cells, cuprous ions are either sequestrated by molecules such as metallothioneins or targeted to utilization pathways by chaperons such as Atox1, Cox17, and CCS. Copper metabolism must be tightly controlled in order to achieve homeostasis and avoid disorders. A hereditary or acquired copper unbalance, including deficiency, overload, or misdistribution, may cause or aggravate certain diseases such as Menkes disease, Wilson disease, neurodegenerative diseases, anemia, metabolic syndrome, cardiovascular diseases, and cancer. A full understanding of copper metabolism and its roles in diseases underlies the identification of novel effective therapies for such diseases. Keywords Copper . Metabolism . Homeostasis . Chaperon . Transporter
Introduction As a transition metal, copper (Cu) plays several key roles in the human body. These various roles are due Ji Chen, Yunhui Jiang and Hua Shi contributed equally to this work. * Chenghua Li [email protected] 1
Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China
2
Department of Medical Oncology, The Seventh People’s Hospital of Chengdu, Chengdu 610041, China
3
Pathology Department, The Second People’s Hospital of Jingmen, Jingmen 448000, China
4
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China
5
Department of General Surgery, The Second People’s Hospital of Jingmen, Jingmen 448000, China
to its two oxidation states, Cu(I)/Cu+ (cuprous ion) and Cu(II)/Cu2+ (cupric ion), which endow it with the ability to act as either a recipient or a donor of electrons. Cu+ prefers to bind t
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