INSIGHTS INTO MYELOPEROXIDASE BIOSYNTHESIS FROM ITS INHERITED DEFICIENCY

Myeloperoxidase (MPO) is a heme protein present in the granules of neu trophils and monocytes. The activated neutrophil releases MPO into the phagolysosome or into the extracellular space in response to a variet y of agonists. During concomitant activation of the NADPH-dependent ox idase, 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 beyon d the domain of innate host defense against infection and includes gen eralized inflammatory diseases, atherosclerosis, and degenerative neur ologic diseases. Search of the various data banks using the cDNA seque nce for MPO has uncovered previously unsuspected relationships among p eroxidatively active proteins in widely different species. In addition , application of the analytical tools of cell and molecular biology ha s allowed definition of specific genotypes underlying MPO deficiency a nd the impact of particular mutations on the fate of MPO precursors al ong the biosynthetic pathway. In parallel, such studies have allowed s ignificant advances in understanding of the normal steps in MPO biosyn thesis and intracellular targeting.