On the mechanism of ceruloplasmin-catalyzed oxidations

doi:10.1016/0006-3002(63)90546-8

Biochimica et Biophysica Acta

Volume 77, 1963, Pages 615-628

https://doi.org/10.1016/0006-3002(63)90546-8 Get rights and content

Abstract

1.
1. The ceruloplasmin-catalyzed oxidation of p-phenylenediamine and other related compounds was studied spectrophotometrically and manometrically.
2.
2. For p-phenylenediamine, the reaction sequence proceeded through three stages. The first probably involved the formation of a charge-transfer complex between substrate and ceruloplasmin Cu²⁺. The second involved the transfer of a single electron from substrate to Cu²⁺ to form a yellow free radical, as determined using electron paramagnetic resonance techniques. The third step involved the loss of another electron from the yellow free radical, either through a disproportionation process or by reaction with enzyme, to form a short-lived diradical species that reacted with more p-phenylenediamine to form a stable purple product.
3.
3. The purple product formed in p-phenylenediamine oxidation can act as an inhibitor for the oxidation of p-phenylenediamine and other substrates.
4.
4. The oxidative sequence of durenediamine was similar to that for p-phenylenediamine, except here the diradical that formed rearranged and hydrolyzed in water to form duroquinone and ammonia.

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The autoxidation of N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) at neutral pH has been shown to generate superoxide radical and hydrogen peroxide. The rate of formation of these species was increased in the presence of certain iron and copper compounds; in the presence of iron complexed with EDTA, hydroxyl radical was also produced. Hydrogen peroxide was detected in erythrocytes incubated with TMPD and these cells suffered oxidative damage as reflected by methaemoglobin formation and glutathione depletion; the one-electron oxidation product of TMPD, Wurster's Blue, was equally effective in producing such changes in erythrocytes. N-Methylated p-phenylenediamines are known to be mutagenic and myotoxic, and it is suggested that ‘active oxygen’ species may be involved in the initiation of these harmful effects.
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Ceruloplasmin was purified and resolved into two forms, ceruloplasmin I and ceruloplasmin II, according to the order of elution by chromatography on DEAE-cellulose, hydroxylapatite and Sephadex G-150 from pigs ranging in age from 2 days to 10 weeks. The sera of the 2-day-old pigs contained only one form of ceruloplasmin, ceruloplasmin II. As the pigs grew older and the overall level of ceruloplasmin increased, the amount of ceruloplasmin II remained relatively constant, while the level of ceruloplasmin I increased dramatically. The two forms of ceruloplasmin differed in their specific enzymatic activity towards $p- phenylenediamine$ and in their copper content, with ceruloplasmin I being the greater in both cases.
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On the mechanism of ceruloplasmin-catalyzed oxidations

Abstract

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Arch. Biochem. Biophys.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Mol. Biol.

Anal. Biochem.

Acta Chem. Scand.

J. Lab. Clin. Med.

Acta Chem. Scand.

Biochem. J.

Bell System. Tech. J.

Biochem. J.

Biochem. J.