Functional genomics of human myeloperoxidase and lactoperoxidase.

摘要

Heme-containing peroxidases are enzymes that use hydrogen peroxide to oxidize organic or inorganic substrates. Eosinophil peroxidase (EPX), lactoperoxidase (LPO), and myeloperoxidase (MPO) constitute a family of enzymes, which are closely related in nucleotide sequence. Neutrophils are the major blood cell type expressing MPO, while LPO is an important enzyme of human milk and other secretions. Both MPO and LPO function to kill bacteria, by catalyzing the formation of reactive cytotoxic oxidants, such as HOCl and HOSCN. These enzymes can also catalyze the oxidative bioactivation of environmental mutagens, such as aromatic amines and polycyclic aromatic hydrocarbons. Human genetic variations in the coding sequences of these enzymes might be associated with differences in susceptibility to environmental mutagenesis. Several coding sequence variants of LPO have been reported on the Environmental Genome Project database (www.niehs.nih.gov/envgenom/) and we explored the functional significance of some of these polymorphisms. Three of the LPO single nucleotide polymorphisms (SNPs) occur in sequences that are highly conserved among the three human peroxidases: R414Q, V421M, and R514Q. Wild-type and variant recombinant human lactoperoxidase SNPs were expressed successfully using a baculovirus system, partially purified by cation exchange chromatography, and compared with respect to specific activities, absorption spectra, and pH stability assays. This research will aid in understanding how these SNPs affect the catalytic function of LPO.