title: Phosphate inhibits in vitro Fe3+ loading into transferrin by forming a soluble Fe(III)-phosphate complex: a potential non-transferrin bound iron species.
abstract: In chronic kidney diseases, NTBI can occur even when total iron levels in serum are low and transferrin is not saturated. We postulated that elevated serum phosphate concentrations, present in CKD patients, might disrupt Fe(3+) loading into apo-transferrin by forming Fe(III)-phosphate species. We report that phosphate competes with apo-transferrin for Fe(3+) by forming a soluble Fe(III)-phosphate complex. Once formed, the Fe(III)-phosphate complex is not a substrate for donating Fe(3+) to apo-transferrin. Phosphate (1-10mM) does not chelate Fe(III) from diferric transferrin under the conditions examined. Complexed forms of Fe(3+), such as iron nitrilotriacetic acid (Fe(3+)-NTA), and Fe(III)-citrate are not susceptible to this phosphate complexation reaction and efficiently deliver Fe(3+) to apo-transferrin in the presence of phosphate. This reaction suggests that citrate might play an important role in protecting against Fe(III), phosphate interactions in vivo. In contrast to the reactions of Fe(3+) and phosphate, the addition of Fe(2+) to a solution of apo-transferrin and phosphate lead to rapid oxidation and deposition of Fe(3+) into apo-transferrin. These in vitro data suggest that, in principle, elevated phosphate concentrations can influence the ability of apo-transferrin to bind iron, depending on the oxidation state of the iron.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hilton
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Seare
authors.forename: N David
authors.initials: ND
authors.lastname: Andros
authors.forename: Zachary
authors.initials: Z
authors.lastname: Kenealey
authors.forename: Catalina Matias
authors.initials: CM
authors.lastname: Orozco
authors.forename: Michael
authors.initials: M
authors.lastname: Webb
authors.forename: Richard K
authors.initials: RK
authors.lastname: Watt
mesh_terms: D006801:Humans; D007501:Iron / Q000097:blood / Q000737:chemistry*; D010084:Oxidation-Reduction; D010710:Phosphates / Q000097:blood / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010710:Phosphates; D014168:Transferrin; D007501:Iron