The reaction of HOCl and cyanocobalamin: Corrin destruction and the liberation of cyanogen chloride

Husam M. Abu-Soud, Dhiman Maitra, Jaeman Byun, Carlos Eduardo A. Souza, Jashoman Banerjee, Ghassan M. Saed, Michael P. Diamond, Peter R. Andreana, Subramaniam Pennathur

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Overproduction of hypochlorous acid (HOCl) has been associated with the development of a variety of disorders such as inflammation, heart disease, pulmonary fibrosis, and cancer through its ability to modify various biomolecules. HOCl is a potent oxidant generated by the myeloperoxidase-hydrogen peroxide-chloride system. Recently, we have provided evidence to support the important link between higher levels of HOCl and heme destruction and free iron release from hemoglobin and RBCs. Our current findings extend this work and show the ability of HOCl to mediate the destruction of metal-ion derivatives of tetrapyrrole macrocyclic rings, such as cyanocobalamin (Cobl), a common pharmacological form of vitamin B12. Cyanocobalamin is a water-soluble vitamin that plays an essential role as an enzyme cofactor and antioxidant, modulating nucleic acid metabolism and gene regulation. It is widely used as a therapeutic agent and supplement, because of its efficacy and stability. In this report, we demonstrate that although Cobl can be an excellent antioxidant, exposure to high levels of HOCl can overcome the beneficial effects of Cobl and generate proinflammatory reaction products. Our rapid kinetic, HPLC, and mass spectrometric analyses showed that HOCl can mediate corrin ring destruction and liberate cyanogen chloride (CNCl) through a mechanism that initially involves α-axial ligand replacement in Cobl to form a chlorinated derivative, hydrolysis, and cleavage of the phosphonucleotide moiety. Additionally, it can liberate free Co, which can perpetuate metal-ion-induced oxidant stress. Taken together, these results are the first report of the generation of toxic molecular products through the interaction of Cobl with HOCl.

Original languageEnglish (US)
Pages (from-to)616-625
Number of pages10
JournalFree Radical Biology and Medicine
Volume52
Issue number3
DOIs
StatePublished - Feb 1 2012

Fingerprint

Hypochlorous Acid
Vitamin B 12
Oxidants
Metal ions
Antioxidants
Metals
Tetrapyrroles
Ions
Derivatives
Pulmonary diseases
Hydrochloric Acid
Pulmonary Fibrosis
Poisons
Coenzymes
Biomolecules
corrin
cyanogen chloride
Heme
Reaction products
Metabolism

Keywords

  • Aging
  • Cobalt
  • Corrin
  • Cyanogen chloride
  • Free metal toxicity
  • Free radicals
  • Inflammation
  • Mammalian peroxidases
  • Mass spectrometry
  • Oxidative stress
  • Porphyrin
  • Stopped-flow
  • Vitamin B12

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Abu-Soud, H. M., Maitra, D., Byun, J., Souza, C. E. A., Banerjee, J., Saed, G. M., ... Pennathur, S. (2012). The reaction of HOCl and cyanocobalamin: Corrin destruction and the liberation of cyanogen chloride. Free Radical Biology and Medicine, 52(3), 616-625. https://doi.org/10.1016/j.freeradbiomed.2011.10.496

The reaction of HOCl and cyanocobalamin : Corrin destruction and the liberation of cyanogen chloride. / Abu-Soud, Husam M.; Maitra, Dhiman; Byun, Jaeman; Souza, Carlos Eduardo A.; Banerjee, Jashoman; Saed, Ghassan M.; Diamond, Michael P.; Andreana, Peter R.; Pennathur, Subramaniam.

In: Free Radical Biology and Medicine, Vol. 52, No. 3, 01.02.2012, p. 616-625.

Research output: Contribution to journalArticle

Abu-Soud, HM, Maitra, D, Byun, J, Souza, CEA, Banerjee, J, Saed, GM, Diamond, MP, Andreana, PR & Pennathur, S 2012, 'The reaction of HOCl and cyanocobalamin: Corrin destruction and the liberation of cyanogen chloride', Free Radical Biology and Medicine, vol. 52, no. 3, pp. 616-625. https://doi.org/10.1016/j.freeradbiomed.2011.10.496
Abu-Soud, Husam M. ; Maitra, Dhiman ; Byun, Jaeman ; Souza, Carlos Eduardo A. ; Banerjee, Jashoman ; Saed, Ghassan M. ; Diamond, Michael P. ; Andreana, Peter R. ; Pennathur, Subramaniam. / The reaction of HOCl and cyanocobalamin : Corrin destruction and the liberation of cyanogen chloride. In: Free Radical Biology and Medicine. 2012 ; Vol. 52, No. 3. pp. 616-625.
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