[Cytochrome P-450 and oxidative modification of macromolecules]

Depending on the localization and functional value, the reactions of the oxidative modification of macromolecules may be classified into two large groups: intracellular and extracellular. To exemplify the first-group reactions, cytochrome P-450 was studied, which is capable of generating different active forms of oxygen during the catalytic cycle. These forms were found to have bactericidal effects and to be able to cause DNA molecule break. In the course of the reaction, cytochrome P-450 also became inactivated under the effect of active oxygen. The involvement of hydrogen peroxide forming directly during peroxycomplex breakdown was proved. It was shown using a soluble reconstructed system that cytochrome P-450 inactivation is attended with the hemoprotein molecule decomposition, destruction and loss of heme, and a rise in the proteolytic vulnerability of the protein. The second reaction group was exemplified by human leucocyte myeloperoxidase which generated hypochlorite along with the active forms of oxygen. Myeloperoxidase showed its bactericidal effect against different strains of bacteria and fungi. The Ames test revealed mutagenic effects of the active oxygen forms generated by myeloperoxidase. In the course of the myeloperoxidase reaction, DNA degradation followed by splitting of the polynucleotide chain and specific pulling out of thymine residues were observed.