**7. References**


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36 Lipid Metabolism

**Author details** 

**7. References** 

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*Clinical Investigation,* 1994, 93(2):844-851.

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In conclusion, increasing the level of endogenous antioxidants, as recently suggested via the supplimentation of weak "pro-oxidants" [8], and not chronic supplementation with large dose of exogenous antioxidants could become in the future a more appropriate approach to

[1] Anderson EJ, Katunga LA, Willis MS. Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart. *Clin Exp Pharmacol Physiol* 2012,

[2] Chae CU, Albert CM, Moorthy MV, Lee IM, Buring JE – Vitamin E supplementation

[3] Cheesman KH, Slater TF - An introduction to free radical biochemistry, in *Free radicals* 

[4] Fritz KS, Petersen DR. Exploring the biology of lipid peroxidation-derived protein

[5] Fulbert J C, Cals M-J - Les radicaux libres en biologie clinique: origine, role pathogene

[6] Gutteridge JM, Halliwell B. Antioxidants: Molecules, medicines, and myths. *Biochem* 

[7] Halliwel B, Gutteridge C, Cross C - Free radicals, antioxidants and human disease.

[8] Halliwell B. Free radicals and antioxidants: updating a personal view. *Nutr Rev* 2012,

[9] Holley A, Cheesman K H - Measuring free radical reactions in vivo, in *Free radicals in* 

[10] 10.Kawada T - Oxidative stress markers and cardiovascular disease: advantage of using these factors in combination with lifestyle factors for cardiovascular risk assessment. *Int* 

[11] Keaney JF Jr, Gaziano JM, Xu A, Frei B, Curran-Celentano J, Shwaery GT, Loscalzo J, Vita JA – Low dose alpha-tocopherol improves and high-dose alpha tocopherol worsens endothelial dependent vasodilator function in cholesterol-fed rabbits. *Journal of* 

and the risk of heart failure in women *Circ Heart Fail* 2012, 5(2): 176-82.

treat diseases that share oxidative stress as a common denominator.

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#### 38 Lipid Metabolism

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**Chapter 3** 

© 2013 Lutsenko and Burkhead, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**The Role of Copper as a Modifier** 

Dietary copper enters the body largely through the small intestine. Two membrane transporters are essential for this process. The high affinity copper uptake protein Ctr1 is responsible for making copper that enters via the apical membrane available in the cytosol for further utilization (1), whereas the copper-transporting ATPase ATP7A facilitates copper exit from the enterocytes into circulation (2) (Figure 1). Complete genetic inactivation of either transporter in experimental animals is embryonically lethal (3-5). However, partial inactivation or tissue specific inactivation of ATP7A or Ctr1, respectively, in either case is associated with copper accumulation in the intestine, impaired copper entry into the bloodstream, and severe copper deficiency in many organs and tissues (1). Copper deficiency, in turn, produces distinct metabolic changes that are discussed in detail in the

The majority of absorbed dietary copper is initially delivered to the liver. Hepatocytes utilize copper for their metabolic needs (such as respiration and radical defense); they also synthesize and secrete the major copper containing protein in serum, ceruloplasmin, and prevent copper overload in the body by exporting excess copper via the canalicular membrane into the bile (Figure 1). These two important functions of hepatocytes (the production of ceruloplasmin and the removal of excess copper) are performed by another transporter, the copper transporting ATPase ATP7B, which is homologous to ATP7A (6, 7). Inactivation of ATP7B in patients with Wilson's disease and in animal models is associated with marked copper overload in the liver and pathologic changes including marked lipid dysregulation in the liver and the serum (discussed in the later

and reproduction in any medium, provided the original work is properly cited.

**of Lipid Metabolism** 

http://dx.doi.org/10.5772/51819

**1. Introduction** 

following sections.

sections).

Jason L. Burkhead and Svetlana Lutsenko

Additional information is available at the end of the chapter

**1.1. Copper homeostasis in mammals** 

[28] Yung LM, Leung FP, Yao X, Chen ZY, Huang Y. Reactive oxygen species in vascular wall. *Cardiovasc Hematol Disord Drug Tagets*. 2006, 6(1): 1-19.
