Ceruloplasmin: the copper transport protein with essential oxidase activity

Adv Enzymol Relat Areas Mol Biol. 1976:44:187-236. doi: 10.1002/9780470122891.ch6.

Abstract

Ceruloplasmin, the blue copper-protein of vertebrate plasma, has been reviewed mainly from a functional point of view. However we have surveyed the chemistry and state copper in the molecule because of the implications of the recent data of Ryden (13,28). His observations suggest that unless special precautions are taken in the isolation of ceruloplasmin degradation, probably proteolytic, produces fragments of various sizes. When isolated, these fragments appear to be held together by noncovalent interactions. Comparison of their catalytic and spectral properties reveals no significant differences from a single homogeneous species of molecular weight of 134,000 isolated by Ryden's methods. On the other hand, the homogeneous molecule may differ in properties highly sensitive to conformation and three-dimensional parameters. Three types of copper atoms have been identified in ceruloplasmin, but their amino acid environment is still unknown. Ceruloplasmin possesses significant oxidase activity towards Fe(II) and numerous aromatic amines and phenols. Its ferroxidase activity has led to the discovery that it is a molecular link between copper and iron metabolism. Ceruloplasmin mobilizes iron into the plasma from iron storage cells in the liver. An equally important duty is that ceruloplasmin, after its rapid biosynthesis in the liver, serves as a major copper transport vehicle, comparable to transferrin. Evidence is accumulating that the copper atoms of ceruloplasmin are a prerequisite for copper utilization in the biosynthesis of cytochrome oxidase and other copper proteins. The ability of ceruloplasmin to release copper at specific cellular sites may be related to its broad substrate spectrum of biological reducing agents. A possible third role of ceruloplasmin is as a contributor to the regulation of the balance of biogenic amines through its oxidase action on the epinephrine and the hydroxyindole series. Thus ceruloplasmin is a copper-protein with several important functions, all of which are directly related to its oxidase activity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Biogenic Amines / metabolism
  • Biological Evolution
  • Biological Transport, Active
  • Carbohydrates / analysis
  • Cations, Divalent
  • Ceruloplasmin / metabolism*
  • Copper / metabolism*
  • Enzyme Activation / drug effects
  • Hemoglobins / metabolism
  • Iron / metabolism
  • Iron / pharmacology
  • Kinetics
  • Liver / metabolism
  • Macromolecular Substances
  • Mathematics
  • Molecular Weight
  • Oxidoreductases / metabolism*
  • Protein Binding
  • Protein Conformation
  • Rats
  • Structure-Activity Relationship

Substances

  • Biogenic Amines
  • Carbohydrates
  • Cations, Divalent
  • Hemoglobins
  • Macromolecular Substances
  • Copper
  • Iron
  • Oxidoreductases
  • Ceruloplasmin