The role of transferrin in heme transport.
Porphyrin accumulation by proliferating cells, e.g., those associated with cancers or wounds, tends to correlate with increased transferrin receptor density. To determine whether transferrin might be implicated in porphyrin transport, fluorescence and absorption spectroscopy were used to study the interaction of porphyrins with transferrin. A single high-affinity binding site for heme and other porphyrins (Kd approximately 20-25 nM) was detected by fluorescence spectroscopy. Difference spectroscopy revealed three additional heme-binding sites. These sites were distinct from the iron-binding sites: 1) Apotransferrin and diferric transferrin bound porphyrins with equal affinity; 2) 59Fe was not displaced from transferrin by porphyrins. Murine erythroleukemia cells incubated with [59Fe]hemin-[125I]transferrin internalized both labels concomitantly. Accumulation of [59Fe]hemin could be blocked by a 100-fold excess of diferric transferrin but not by apotransferrin. These results indicate that cells can internalize exogenous heme, and possibly porphyrins, bound to transferrin via its receptor.
Stout
D L
DL
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D006418:Heme / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D011166:Porphyrins / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D011166:Porphyrins; D011990:Receptors, Transferrin; D014168:Transferrin; D006418:Heme