Protein ceruloplasmin

Lovstad, R.A. (1984). Catecholamine stimulation of copper-dependent haemolysis protective action of superoxide dismutase, catalase, hydroxyl radical scavengers and scrum proteins (ceruloplasmin, albumin and apotransferrin). Acta Pharmacol. Toxicol. 54, 340-345. 

A copper-binding protein, ceruloplasmin, which is a blood serum protein, has been demonstrated in milk by immunodiffusion techniques (Hanson et al. 1967 Poulik and Weiss 1975). It may be the enzyme ferroxidase (EC 1.16.3.1). 

Factor IXa causes a rapid activation of factor X only if Ca2+, phospholipid,553 554 and the accessory factor Villa555 are present. The IXa Villa complex acts on X about 2 x 105 times faster than does IXa alone. This complex cleaves the same bonds in X as does the VIIa Va complex formed in the tissue factor pathway.514 The 2332-residue factor VIII and factor V have similar structures that include three repeats of a domain homologous to the blue copper-containing plasma protein ceruloplasmin (Chapter 16).556-559 Tyrosine 1680 of VIII apparently must be converted to a sulfate ester for full activity.560... 

Hypoproteinemia may result in low levels of serum calcium, ceruloplasmin, and transferrin. Because losses of iron are at most 0.5-1.0 mg/24 hr, even with the heaviest proteinuria, other factors must operate to produce iron deficiency and microcytic hypochromic anemia. Although the copper-binding protein ceruloplasmin is lost in the urine in nephrotic subjects and its plasma levels are low, plasma and red cell copper concentrations are usually normal. Zinc circulates mainly bound to albumin and also to transferrin, and thus the reported reduction zinc concentration in plasma, hair, and white cells in nephrotic patients is not surprising. 

Thrombin (MW 39,000) is a proteolytic enzyme of the serine protease group. It is derived from prothrombin, a circulating plasma protein, through the proteolytic action of a complex consisting of the proteolytic enzyme factor X (or factor Xa), another protein called factor V (accelerator protein), calcium, and phospholipid. Factor V has recently been identified as the plasma copper protein ceruloplasmin or a similar protein (see Chapter 6). 

A few years ago optical intermediates in the reactions between the reduced enzymes and dioxygen were detected with laccase (21) and with the related protein ceruloplasmin (22). It was tentatively suggested that they represent H202 or one of its ions bound to a metal ion in the enzymes. With cytochrome oxidase, the search for a functional intermediate also has presented greater problems, and it is only recently that Chance and associates (23) have been able to report substantial progress... 

Metal-binding proteins Ceruloplasmin Ferritin Hemoglobin Lactoferrin Metallotheinein Myoglobin Transferrin... 

Recent reviews on copper homeostasis in E. col and yeast are available. Copper and iron metabolism are often intertwined. For instance, mammalian iron metabohsm depends on the copper protein, ceruloplasmin, a ferroxidase that facilitates iron efflux from cells see Copper Proteins Oxidases) Several important human diseases, including Menkes disease and Wilson s disease, result from mutations in copper transport see Metal-related Diseases of Genetic Origin) ... 

Copper is a reddish metallic element (symbol Cu atomic no. 29). Its symbol derives from the Latin word cuprum, because it was originally discovered in Cyprus. It is widely found as different salts in minerals such as atacamite (chloride) azurite and malachite (carbonates) bornite, chalco-cite, chalcopjrite, stannite, tennantite, and tetrahedrite (sulfides) chalcanthite (sulfate) dioptase (silicate) erinite and olivenite (arsenates) tenorite (oxide) torbernite (phosphate) and zorgite (selenide). Copper is an essential constituent of several enzymes. It is carried in the blood by a specific copper-binding protein, ceruloplasmin. 

If one had to state an overall role of copper in the body, one might say oxygen metabolism. One major factor shared by both zinc and copper is that both metal ions occur bound to metallothionein. The function of metallothionein is not firmly established. Copper is bound to another protein, ceruloplasmin, which occurs in the cell and plasma. The function of this protein is not clear either. Zinc absorption, as iron absorption, is impaired by high levels of phytic acid. Copper absorption is not inhibited by phytic acid. The major route of excretion of both metal ions is fecal, rather than urinary. 

Iron entering the bloodstream from the gastrointestinal tract is thought to be present as Fe , and must be oxidized to Fe before binding to transferrin, which then delivers iron to many different types of cell. The non-enzymic route for oxidation of Fe in serum appears to be too slow for the formation of iron(III) transferrin. As noted in Section 62.1.8.5.1, the copper protein ceruloplasmin has ferroxidase activity, being responsible for the oxidation of Fe" to Fe . It is well known that deficiency of copper influences iron metabolism in animals, in accord with this role for ceruloplasmin. 

Antioxidant Functions, Both intracellular and extracellular SODs are copper- and zinc-containing enzymes, able to convert superoxide radicals to hydrogen peroxide, which can be subsequently removed by catalase and other antioxidant defenses. The plasma protein ceruloplasmin also binds copper ions and thus prevents oxidative damage from free copper ions, which can generate hydroxyl radicals. 

Plasma Cu levels in rats are low at birth and increase sharply after postnatal day 10, concomitantly with the Cu storage protein ceruloplasmin. In contrast, plasma Zn levels were highest at birth and decreased slowly to adult values [26]. Older rats (20-22 months) have also been shown to have lower total plasma Fe content than middle aged rats (8-10 months), in addition to lower levels of the Fe-containing protein, hemoglobin [27]. 

Some of the methods of investigation essential for the study of copper metabolism will be surveyed in this chapter. In addition to the analytical methods for the detection and quantitative determination of copper in biological materials, the techniques for determination and detection of one of the biologically important copper proteins (ceruloplasmin) will also be discussed. Finally, the general principles and techniques involved in the use of radiocopper will be surveyed. 

ORD and EPR measurements indicated that the ligand field of the single cupric ion is distorted from the regular square-planar configuration [(109) and refs, cited therein similar considerations had been applied to the Cu(II) sites in the copper protein ceruloplasmin (96)]. This could also explain the very intense blue color observed. ORD data in the ultraviolet region indicated little or no helical structure in this plant protein (109). CD spectra of stellacyanin in the range 300 to 1100 nm were reported (98). 

Cu 72 Electron transfer systems (blue copper proteins) O2 storage and transport (haemocyanin) Cu transport proteins (ceruloplasmin)... 

Also the blue copper protein, ceruloplasmin, which is considered the laccase counterpart in the animal kingdom, could oxidise HA. The seric protein is widespread in animals and has been studied in depth, but its actual physiological role is far from being understood. It shows a wide substrate specificity [223-224], The ability of ceruloplasmin to oxidise HA has been demonstrated [201], even if this oxidation is slow and stops when unaltered HA is still present. It has been suggested that the protein could be inactivated by some reactive intermediates in HA oxidation. As noted elsewhere [38], it is reasonable to conclude that HA / ceruloplasmin interaction, if existing, would be of very little physiological importance. 

Spectrophotometric determination of the protein ceruloplasmin in blood serum. The determination of this protein has replaced the determination of copper in blood serum. 

Transcriptional control of iron metabolism has been described, and therefore IRP is imlikely to be the only iron biosensor in mammals. The serum protein ceruloplasmin is transcriptionally regulated by iron in the human hepatocellular carcinoma line HepG2 [48]. Ceruloplasmin is a ferrous iron oxidase (ferroxidase) involved in both transferrin-dependent and -independent iron transport, but appears to facilitate only the latter in the carcinoma cell line. The factor(s) that mediate(s) transcriptional control of ceruloplasmin by iron is not yet known. 

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