Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase.

Abstract

Oxidative degradation of biological substrates by HOCl was examined under reaction conditions similar to those found in active phagosomes. Iron sulfur proteins are bleached extremely rapidly, followed in decreasing order by .beta.-carotene, nucleotides, porphyrins and heme proteins. Enzymes containing essential cysteine molecules are inactivated with an effectiveness that roughly parallels the nucleophilic reactivities of their SH groups. Other compounds, including glucosamines, quinones, riboflavin and, except for N-chlorination, phospholipids, are unreactive. Rapid irreversible oxidation of cytochromes, adenine nucleotides and carotene pigments occurs when bacterial cells are exposed to exogenous HOCl with Escherichia coli, titrimetric oxidation of cytochrome coincided with loss of aerobic respiration. The occurrence of these cellular reactions implicates HOCl as a primary microbicide in myeloperoxidase-containing leukocytes; the reactivity patterns observed are consistent with the view that bactericidal action results primarily from loss of energy-linked respiration due to destruction of cellular electron transport chains and the adenine nucleotide pool.