Ceruloplasmin biologic function

The multi-copper oxidases include laccase, ceruloplasmin, and ascorbate oxidase. Laccase can be found in tree sap and in fungi ascorbate oxidase, in cucumber and related plants and ceruloplasmin, in vertebrate blood serum. Laccases catalyze oxidation of phenolic compounds to radicals with a concomitant 4e reduction of O2 to water, and it is thought that this process may be important in the breakdown of lignin. Ceruloplasmin, whose real biological function is either quite varied or unknown, also catalyzes oxidation of a variety of substrates, again via a 4e reduction of O2 to water. Ferroxidase activity has been demonstrated for it, as has SOD activity. Ascorbate oxidase catalyzes the oxidation of ascorbate, again via a 4e reduction of O2 to water. Excellent reviews of these three systems can be found in Volume 111 of Copper Proteins and Copper Enzymes (Lontie, 1984). 

Copper proteins are involved in a variety of biological functions, including electron transport, copper storage and many oxidase activities. A variety of reviews on this topic are available (Sykes, 1985 Chapman, 1991). Several copper proteins are easily identified by their beautiful blue colour and have been labelled blue copper proteins. The blue copper proteins can be divided into two classes, the oxidases (laccase, ascorbate oxidase, ceruloplasmin) and the electron carriers (plastocyanin, stellacyanin, umecyanin, etc.). 

Ceruloplasmin is a multifunctional enzyme capable of oxidizing phenols and aromatic amines (Musci et al., 1999). It can also efficiently oxidize Fe(II) to Fe(III), which is currently considered its main in vivo biological function. The ferroxidase activity of this enzyme was hrst reported in 1960 (Curzon and O Reilly, 1960) and it was later suggested that such activity is important for loading iron into the transferrin, since it binds only Fe(III) (Osaki, 1966). Recent studies on ceruloplasmin knockout mice demonstrated that they indeed exhibit a severe impairment of... 

Type 1 copper proteins are the class of proteins for which cupredoxins were originally named. Type 1 copper proteins include both proteins with known electron transfer function (e.g., plastocyanin and rusticyanin), and proteins whose biological functions have not been determined conclusively (e.g., stellacyanin and plantacyanin). Although these proteins with unknown function cannot be called cupredoxins by the strict functional definition, they have been classified as cupredoxins because they share the same overall structural fold and metal-binding sites as cupredoxins. In addition, many multidomain proteins, such as laccase, ascorbate oxidase, and ceruloplasmin, contain multiple metal centers, one of which is a type 1 copper. Those cupredoxin centers are also included here. Finally, both the Cua center in cytochrome c oxidase (CcO) and nitrous oxide reductase (N2OR), and the red copper center in nitrocyanin will be discussed in this chapter because their metal centers are structurally related to the type 1 copper center and the protein domain that contains both centers share the same overall structural motif as those of cupredoxins. The Cua center also functions as an electron transfer agent. Like ferredoxins, which contain either dinuclear or tetranuclear iron-sulfur centers, cupredoxins may include either the mononuclear or the dinuclear copper center in their metal-binding sites. 

Ceruloplasmin levels are also influenced by hormones. The levels have been found to increase in pregnancy and also in response to administration of estrogen. There are several hypotheses for the biological function of ceruloplasmin. It has been suggested that ceruloplasmin oxidizes ferrous ion to the ferric state, which then goes to bind apotransferrin in blood plasma [10]. There was a... 

The present volume is the fourth in the series and covers the topics lithium in biology, the structure and function of ceruloplasmin, rhenium complexes in nuclear medicine, the anti-HIV activity of macrocyclic polyamines and their metal complexes, platinum anticancer dmgs, and functional model complexes for dinuclear phosphoesterase enzymes. The production of this volume has been overshadowed by a very sad event—the passing away of the senior editor, Professor Robert W. Hay. It was he who conceived the idea of producing this series and who more than anyone else has been responsible for its continuation. A tribute by one of his many friends, Dr. David Richens, is included in this Volume. 

Copper The daily intake from food is 0.8—2.0 mg it is released into the portal vein via copper-transporting ATPase. The transport of copper, which is toxic in its free form, is effected by the binding to ceruloplasmin, albumin and transcuprin. Copper is bound to reduced glutathione and metallothionein in the hepatocytes and distributed to various organelles or incorporated into enzymes. The biological effects of copper are manifold and essential for some cellular functions, (s. p. 50) Copper is toxic not only in its free form, but also in cases of overload (e. g. cirrhosis in childhood due to the consumption of water from copper pipes). Copper homoe-ostasis is regulated via biliary excretion (normal value about 1.2-2.0 mg/day), so that the normal value in serum is 75-130 fg/dl. (321, 323, 370, 383, 386) (s. p. 102)... 

A basic tenet in biology is that structure and function are linked, and the model above is consistent with functional studies on heme uptake from and gene regulation by heme-hemopexin (see below), Thus, with the recent details of the structures of hemopexin (M. Paoli, H. M. Baker, B. F. Anderson, W. T. Morgan, A. Smith, N. Baker, unpublished results) and ceruloplasmin [74], the metal-protein interactions of two key players in redox metal transport and metabolism are now established. 

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