title: Human serum transferrin: is there a link among autism, high oxalate levels, and iron deficiency anemia?
abstract: It has been previously suggested that large amounts of oxalate in plasma could play a role in autism by binding to the bilobal iron transport protein transferrin (hTF), thereby interfering with iron metabolism by inhibiting the delivery of iron to cells. By examining the effect of the substitution of oxalate for the physiologically utilized synergistic carbonate anion in each lobe of hTF, we sought to provide a molecular basis for or against such a role. Our work clearly shows both qualitatively (6 M urea gels) and quantitatively (kinetic analysis by stopped-flow spectrofluorimetry) that the presence of oxalate in place of carbonate in each binding site of hTF does indeed greatly interfere with the removal of iron from each lobe (in the absence and presence of the specific hTF receptor). However, we also clearly demonstrate that once the iron is bound within each lobe of hTF, neither anion can displace the other. Additionally, as verified by urea gels and electrospray mass spectrometry, formation of completely homogeneous hTF-anion complexes requires that all iron must first be removed and hTF then reloaded with iron in the presence of either carbonate or oxalate. Significantly, experiments described here show that carbonate is the preferred binding partner; i.e., even if an equal amount of each anion is available during the iron loading process, the hTF-carbonate complex is formed.
authors.affiliation: Department of Biochemistry, University of Vermont, College of Medicine , 89 Beaumont Avenue, Burlington, Vermont 05405, United States.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Luck
authors.forename: Cedric E
authors.initials: CE
authors.lastname: Bobst
authors.forename: Igor A
authors.initials: IA
authors.lastname: Kaltashov
authors.forename: Anne B
authors.initials: AB
authors.lastname: Mason
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D001321:Autistic Disorder / Q000097:blood*; D002254:Carbonates / Q000378:metabolism*; D002478:Cells, Cultured; D002659:Child Development Disorders, Pervasive / Q000097:blood*; D006224:Cricetinae; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D010070:Oxalates / Q000097:blood*; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002254:Carbonates; D010070:Oxalates; D014168:Transferrin; D007501:Iron