Occupancy of the iron-binding sites of human transferrin in sera obtained from different anatomical sites.

Transferrin is the major iron-transport protein in serum. Four molecular species (apo-, two mono-, and diferric transferrins) can be distinguished on the basis of their occupancy with iron. These species differ physicochemically and in the affinity with which they bind to the transferrin receptor. To elucidate the possible role of the four molecular species in directing the flow of iron between the major anatomical sites of iron release and utilization we have analyzed sera from eight stable multiorgan donors. The samples were obtained from veins draining the spleen, gut, and liver, and from the periphery. Employing polyacrylamide-gel electrophoresis in combination with crossed immunoelectrophoresis we were able to identify the four molecular species in all samples. Apo-transferrin was the predominant molecular species while diferric transferrin was the least abundant (P less than 0.01). The monoferric species were dominated by the acid-stable form (iron loading on the C-terminal end of the molecule) with ratios C/N from 1.2 (splenic and posthepatic serum) to 1.5-1.6 in mesenteric or peripheral samples respectively. We conclude from our study that it is unlikely that the monoferric transferrin species play a role in directing internal iron exchange and that in accordance with most of the literature the acid-stable form is preferentially loaded under physiological conditions of iron metabolism.