Multifunctional roles of the plasma protein, caeruloplasmin, have been briefly reviewed under three main headings. These are protein functions, enzymic activity, and antioxidant protection. As a plasma protein it is said to play a role in the transport of copper. Since some 95 % of serum copper is associated with caeruloplasmin, measurement of the protein provides a useful guide to copper levels. Enzymic functions are related to its oxidase activity. Substrates commonly used for laboratory assay include non-biologically occurring aromatic amines and polyphenols. More recently, a physiological function has been proposed in which the enzyme oxidases iron from the ferrous to ferric state for binding to apotransferrin. This enzymic function of caeruloplasmin has been designated ‘ferroxidase’. In vitro studies have shown that caeruloplasmin can inhibit the peroxidation of polyunsaturated fatty-acids. This function is in part related to its ferroxidase activity. No antioxidant activity has yet been demonstrated in vivo but this possibility is speculatively discussed.
References
1.
Al-TimimiD.DormandyT. L. (1977). The inhibition of lipid autoxidation by human caeruloplasmin. Biochemical Journal, 168, 283–288.
2.
BarrassB. C.CoultO. B. (1972). In Progress in Brain Research, Volume 36, edited by BradleyP. B.BrimbleR. W., pp. 97–104. Elsevier, Amsterdam.
3.
CrocksonR. A.PayneC. J.RatcliffA. P.SoothillJ. F. (1966). The sequence of acute phase reactive proteins following surgical trauma. Clinica Chimica Acta, 14, 435–441.
4.
CurzonG. (1960). The effects of some ions and chelating agents on the oxidase activity of caeruloplasmin. Biochemical Journal, 77, 66–73.
5.
CurzonG.O'ReillyS. (1960). A coupled iron-caeruloplasmin oxidation system. Biochemical and Biophysical Research Communications, 2, 284–286.
6.
FriedenE. (1974). In Protein-metal Interactions, edited by FriedmanM., pp. 1–31. Plenum Press, New York.
7.
FriedenE.HsiehH. S. (1976). Ceruloplasmin: The copper transporting protein with essential oxidase activity. In Advances in Enzymology, Volume 44, edited by MeisterA., pp. 187–236. Wiley, and Sons, London.
8.
GutteridgeJ. M. C. (1976). Superoxide dismutase (erythrocuprein) and free-radicals in clinical chemistry. Annals of Clinical Biochemistry, 13, 393–398.
9.
GutteridgeJ. M. C. (1977a). The measurement of malondialdehyde in peroxidising ox-brain phospholipid liposomes. Analytical Biochemistry, 82, 76–82.
10.
GutteridgeJ. M. C. (1977b). The protective action of superoxide dismutase on metal-ion catalysed peroxidation of phospholipid. Biochemical and Biophysical Research Communications, 77, 379–386.
11.
HalliwellB. (1978). Biochemical mechanisms accounting for the toxic action of oxygen on living organisms: The key role of superoxide dismutases. Cell Biology International Reports, 2, 113–128.
12.
HartE. B.SteenbockH.WaddellJ.ElvehjemC. A. (1928). Iron in nutrition. VII Copper as a supplement to iron for hemoglobin building in the rat. Journal of Biological Chemistry, 77, 797–812.
13.
HolmbergC. G.LaurellC. B. (1948). Investigations in serum copper. II Isolation of the copper containing protein and a description of some of its properties. Acta Chemica Scandinavica, 2, 550–556.
14.
HoltzmanN. A.GaumnitzB. M. (1970). Studies on the rate of release and turnover of ceruloplasmin and apoceruloplasmin in rat plasma. Journal of Biological Chemistry, 245, 2354–2358.
15.
JoesterK. E.JungG.WeberU.WeserU. (1972). Superoxide dismutase activity of Cu-amino acid chelates. Federation of European Biochemical Societies Letters, 25, 25–28.
16.
LovstadR. A. (1975). Kinetic studies on the ceruloplasmin-catalyzed oxidation of phenothiazine derivatives. Biochemical Pharmacology, 24, 475–478.
17.
McDermottJ. A.HuberC. T.OsakiS.FriedenE. (1968). Role of iron in the oxidase activity of ceruloplasmin. Biochimica et Biophysica Acta, 151, 541–557.
18.
McKeeD. J.FriedenE. (1971). Binding of transition metal ions by ceruloplasmin (ferroxidase). Biochemistry, 10, 3880–3883.
19.
OsakiS.JohnsonD. A.FriedenE. (1966). The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. Journal of Biological Chemistry, 241, 2746–2751.
20.
OwenC. A. (1975). Uptake of 67Cu by ceruloplasmin in vitro. Proceedings of the Society for Experimental Biology and Medicine, 149, 681–682.
21.
PlacerZ.SlabochovàZ.VeselkováA. (1964). Der biologische Einfluss der Antioxydantien. Nährung, 8, 333–339.
22.
PoillonW. N.BearnA. G. (1966). The molecular structure of human ceruloplasmin: Evidence for subunits. Biochimica et Biophysica Acta, 127, 407–427.
23.
RaganH. A.NachtS.LessG. R.BishopC. R.CartwrightG. E. (1969). Effect of ceruloplasmin on plasma iron in copper-deficient swine. American Journal of Physiology, 217, 1320–1323.
24.
RiceE. W. (1961). Evaluation of the role of ceruloplasmin as an acute-phase reactant. Clinica Chimica Acta, 6, 652–655.
25.
RoeserH. P.LeeG. R.NachtS.CartwrightG. E. (1970). The role of ceruloplasmin in iron metabolism. Journal of Clinical Investigation, 49, 2408–2417.
26.
RydenL. (1971). Evidence for proteolytic fragments in commercial samples of human ceruloplasmin. Federation of European Biochemical Societies Letters, 18, 321–325.
27.
ScheinbergI. H.MorellA. G. (1973). In Inorganic Biochemistry, edited by EichornG. I., pp. 306–319. Elsevier, New York.
28.
StocksJ.GutteridgeJ. M. C.SharpR. J.DormandyT. L. (1974). The inhibition of lipid autoxidation by human serum and its relationship to serum proteins and tocopherol. Clinical Science and Molecular Medicine, 47, 223–233.
29.
VanngardT. (1967). In Magnetic Resonance in Biological Systems, edited by EhrenbergE.MalmströmE. C.VanngardT., p. 213. Pergamon Press, Oxford.
30.
VidlákováM.ErazimováJ.HorkyJ.PlacerZ. (1972). Relationship of serum antioxidative activity to tocopherol and serum inhibitor of lipid peroxidation. Clinica Chimica Acta, 36, 61–66.
31.
YoungG.CurzonG. (1972). A method for obtaining linear reciprocal plots with caeruloplasmin and its application in the study of the kinetic parameters of caeruloplasmin substrates. Biochemical Journal, 129, 273–283.
