| pubmed-article:6412761 | pubmed:abstractText | Rabbit hemoglobin effects reduced pyridine nucleotide-dependent N-oxidation of 4-chloroaniline in the presence of NADPH-cytochrome c (P-450) reductase (EC 1.6.2.4). The reaction is blocked by the addition of CO, superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6). The apparent Km value for the amine is 5.9 mM. The substrate interacts with hemoglobin in a non-cooperative manner; highly purified alpha- and beta-subunits mediate amine oxidation with kinetic constants close to those of the intact tetramer. Metabolism of 4-chloroaniline is associated with the formation of a 421 nm absorbing spectral complex, which might represent a ferryl species or a product adduct. Rapid reaction measurements suggests that either transfer of the second electron or product dissociation limits the overall rate of hemoglobin cycling. Erythrocyte reductases, such as 'NADPH-methemoglobin reductase' or soluble NADH-cytochrome b5 reductase (EC 1.6.2.2), also sustain amine oxidation in the presence of an appropriate electron carrier. Similarly, intact rabbit erythrocytes generate low amounts of N-oxy product when incubated with the parent amine. These findings support the notion that the red blood cell might be a site of bioactivation of aromatic amines, some of which, after being N-oxidized, become potent mutagens and carcinogens. | lld:pubmed |
