Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system
Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by (1) a failure to mobilize iron from iron-loaded transferrin, (2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and (3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species.
- Research Organization:
- Veterans Administration Medical Center, Iowa City, IA (USA)
- OSTI ID:
- 5872707
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 264:16
- Country of Publication:
- United States
- Language:
- English
Similar Records
Luminol-dependent photoemission from single neutrophil stimulated by phorbol ester and calcium ionophore--role of degranulation and myeloperoxidase
Halogenation and proteolysis of complement component C3 on Salmonella typhimurium during phagocytosis by human neutrophils
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
IRON
RECEPTORS
PEROXIDASES
BIOCHEMICAL REACTION KINETICS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
TRANSFERRIN
IODINATION
AMINO ACID SEQUENCE
CATALASE
CATALYSIS
DOGS
IODINE ISOTOPES
MAN
NEUTROPHILS
TRACER TECHNIQUES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CHEMICAL REACTIONS
ELEMENTS
ENZYMES
ESTERS
GLOBULINS
GLOBULINS-BETA
HALOGENATION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
METALLOPROTEINS
METALS
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PRIMATES
PROTEINS
REACTION KINETICS
TRANSITION ELEMENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques