PMID: 2510407Sep 1, 1989Paper

The degradation of haem by carbon tetrachloride: metabolic activation requires a free axial coordination site on the haem iron and electron donation

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
M MannoF De Matteis

Abstract

1. The ability of haem to catalyse the reductive activation of carbon tetrachloride (CCl4) in vitro has been investigated under anaerobic conditions, using methaemalbumin (MHA) and either sodium dithionite or NADPH together with NADPH-cytochrome P-450 reductase (EC 1.6.2.4) as the reducing agents. 2. In the non-enzymic system protohaem and other non-physiological haem analogues underwent rapid and extensive CCl4-dependent degradation, due to irreversible modification of their porphyrin tetrapyrrolic structure. 3. This mechanism of non-enzymic activation of CCl4 by protohaem mimics that catalyzed by cytochrome P-450 in that it requires a free, reduced haem iron and electron donation and it is largely prevented by carbon monoxide. 4. H.p.l.c. analysis of 14C-haem after anaerobic incubation with CCl4 and sodium dithionite gave radioactive products which eluted before and after haem, and exhibited significantly lower absorbance at 400 nm compared with authentic haem. When the products of CCl4-dependent haem degradation were methylated and applied to silica for t.l.c., two non-fluorescent pigments were isolated, purified and partially characterized. 5. On incubation of haem with 14CCl4 and sodium dithionite a 1:1 stoichiometry could...Continue Reading

References

Oct 1, 1968·Proceedings of the National Academy of Sciences of the United States of America·R TenhunenR Schmid
Aug 29, 1980·Biochemical and Biophysical Research Communications·D MansuyJ C Chottard
Oct 1, 1955·Archives of Biochemistry and Biophysics·A ROSSI-FANELLI, E ANTONINI
Nov 1, 1957·Biochimica Et Biophysica Acta·R F LABBE, G NISHIDA
Aug 1, 1965·Analytical Chemistry·G R MORRISON

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Citations

Jan 1, 1990·Pharmacology & Therapeutics·P R Ortiz de Montellano
Aug 16, 2003·Toxicology Letters·Alberta ZanovelloMaurizio Manno
Nov 19, 2004·Antioxidants & Redox Signaling·Enika Nagababu, Joseph M Rifkind
Jan 1, 1995·Critical Reviews in Toxicology·A R GoeptarN P Vermeulen
Apr 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R TolandoM Manno

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