Insights into myeloperoxidase biosynthesis from its inherited deficiency.
Myeloperoxidase (MPO) is a heme protein present in the granules of neutrophils and monocytes. The activated neutrophil releases MPO into the phagolysosome or into the extracellular space in response to a variety of agonists. During concomitant activation of the NADPH-dependent oxidase, the stimulated neutrophil also generates hydrogen peroxide, and in this way the MPO-hydrogen peroxide-halide system exerts its potent microbicidal activity. Recent interest in MPO has extended well beyond the domain of innate host defense against infection and includes generalized inflammatory diseases, atherosclerosis, and degenerative neurologic diseases. Search of the various data banks using the cDNA sequence for MPO has uncovered previously unsuspected relationships among peroxidatively active proteins in widely different species. In addition, application of the analytical tools of cell and molecular biology has allowed definition of specific genotypes underlying MPO deficiency and the impact of particular mutations on the fate of MPO precursors along the biosynthetic pathway. In parallel, such studies have allowed significant advances in understanding of the normal steps in MPO biosynthesis and intracellular targeting.
Department of Medicine, University of Iowa and Veterans Administration Medical Center, Iowa City 52242, USA.
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D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000096:biosynthesis* / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics
D018076:DNA, Complementary; D009195:Peroxidase