Copper normal transport

Contrary to popular belief, ceruloplasmin5, the principal copper-containing protein in plasma, ceruloplasmin, is not involved in copper transport. This is clearly underlined by the clinical observation that patients with aceruloplasminaemia (i.e. lacking ceruloplasmin in their blood) have perfectly normal copper metabolism and homeostasis. Copper is transported in plasma mostly by serum albumin with smaller amounts bound to low-molecular weight ligands like histidine. Likewise zinc is mostly transported in plasma bound to proteins (albumin and ot2-macroglobulin). 

The role of Cu as an essential trace element has focused attention on possible roles for copper chelation of biologically active ligands, with subsequent interference of normal transport and distribution, as well as the role of the metal in redox reactions due to the accessible oxidation states of (I) and (II). Similarly, the physiological response of copper levels in disease conditions [50] and the overall role of trace metals in health and disease [51, 52] are relevant and of considerable importance. The increase in serum copper content in infections, arthritic diseases, and certain neoplasms is well documented and, in fact, the subsequent decrease in level upon treatment has been used successfully as an indicator of cancer remission [50]. Copper complexes may be effective in therapy due in part to their ability to mimic this physiological response of elevated copper [53] and, clearly, the interplay of introduced copper with pre-existent bound copper and effects on copper—protein mediated processes will affect the ultimate biological fate of the complex. Likewise, while the excess accumulation of free Cu, and indeed Fe and Zn, caused by malfunction or absence of normal metabolic pathways is extremely damaging to the body, the controlled release of such metals may be beneficially cytotoxic. The widespread pharmacological effects of copper complexes have been briefly reviewed [54]. 

Albumin is a major transport facilitator of hydrophobic compounds which would otherwise disrupt cellular membranes. These compounds include free fatty acids and bilirubin as well as hormones such as cortisol, aldosterone, and thyroxine when these materials have exceeded the capacity of proteins normally associated with them. Albumin also binds ions, including toxic heavy metals and metals such as copper and zinc which are essential for normal physiological functioning but may be toxic in quantities in excess of their binding capacity for their carrier proteins. Binding of protons is the basis for the buffering capacity of albumin. 

This blue oxidase, present in the plasma of vertebrates, appears to be multifunctional.905,975 It accounts for some 95% of the circulating copper in a normal mammal, and its concentration fluctuates considerably in diseased states. It appears that ceruloplasmin has a major role in copper transport (as discussed in Section 62.1.11). In addition it has oxidase activity towards three groups of substrates, although its physiological role is not known with certainty. 

Copper is an essential trace element absorbed in the gut and transported to the liver bound to albumin. It is found in a variety of enzymes, including superoxide dismutase. In the bloodstream Cu is present mostly in ceruloplasmin. Tissues with a relatively high content of Cu are liver, heart, and brain. The RDA for Cu in normal, healthy adults is 0.9 mg day-1, but newborns usually have liver levels higher than those of adults. The concentration of Cu in mature milk ranges between 0.2 and 0.3 mg l-1 in colostrum it is higher (0.4-0.6 mg l-1), but decreases along the lactation period (see the Chapter 13 by de la Flor St Remy et al.). 

There are several modes of protection from the activity of available iron or copper in vivo. (Antioxidant action is discussed in more detail in Chapter 4). Apotransferrin binds iron(III) for transport and delivery to cells. It is its capacity as an iron-binding protein which renders it also able to function as an antioxidant by making iron(III) unavailable for participation in iron-catalysed radical reactions. Only about 30% of the iron-binding sites on the transferrin in human plasma are normally occupied in vivo (transferrin concentration 1.2-2.0mg/ml). The copper-containing protein caeruloplasmin (0.2-0.4 mg/ml) is... 

Laboratory data demonstrating copper limitation of marine phytoplankton are rare. It has generally been difficult to limit the growth rates of cultures by lowering the copper concentration in the medium, indicating a very low absolute copper requirement and/or a very effective uptake system in most species (Sunda and Huntsman, 1995c). If, as predicted, plastocyanin normally accounts for a major fraction of the copper quota of phytoplankton, a low-copper requirement would result from the known ability to replace plastocyanin by cytochrome c in the electron transport chain of the light reaction in a number of taxa. 

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