Actinides, transferrin binding

The mechanisms of actinide/lanthanide binding to transferrin may not be the same as that for ironflll)... 

The mechanisms of actinide/lanthanide binding to transferrin may not be the same as that for iron( III). Spectroscopic studies by Duffield and Taylor(1987) have shown the fine details of Pu(IV) and Th(IV) binding to transferrin to be very similar to that of Fe(III). 

The actinides plutonium, neptunium, protoactinium, and thorium (151,173) bind to transferrin. The larger Th4+ ion (radius, 0.94 A) still binds to both sites, although binding to the second site (probably the N-terminal site) is significantly weaker than that to the first and apparently involves only one Tyr ligand compared with two Tyr in the other (151). Although UV difference spectra for Pu4+ are equivocal (174), it seems likely that two Pu4+ are bound. The likely carrier properties of transferrin for Pu4+ makes the design of competitive chelators of some importance (151). 

In addition to binding and transporting Fe + ions, transferrin is also responsible for binding certain of the actinide and lanthanide ions in viva, much evidence having been gleaned from animal studies by Taylor et al. (1987) and Taylor (1991). These studies have shown transferrin to bind Pu, Np, Pa in rat plasma. Evidence for Th(IV) binding to transferrin has been obtained (Duilield and Taylor 1986) with indications that this protein also binds Cm ", Eu " Gd " and Yb " in plasma (Taylor... 

UV-difference spectroscopy, and other studies in vitro with plutonium (IV), tho-rium(IV) and a number of trivalent lanthanides, have demonstrated that, like iron, two lanthanide or actinide metal atoms are bound per transferrin molecule (Duffield and Taylor 1986, Taylor et al. 1991, Zak and Aisen 1988). Saturation of the lanthanide- or actinide-containing transferrin with excess iron results in a liberation of the f element, thus suggesting that these metals are binding to the two iron-binding sites on the transferrin molecule (Taylor et al. 1991). These studies have also shown that bicarbonate is necessary, as a synergistic anion, for the binding of actinides and lanthanides to transferrin. 

The observations described above have important implications with regard to actinide/lanthanide distributions within the body. It is apparent that in binding to transferrin, the f elements are participating in certain aspects of the iron transport pathways in vivo. However, no plutonium, e.g., is found within red blood cells following incorporation and there is no unequivocal evidence that plutonium and the other actinides or lanthanides are transported into cells via transferrin-receptor-mediated endocytosis (Duffield and Taylor 1986). This, too, is a puzzling aspect of f-element-transferrin chemistry and biochemistry which needs more study. 

The physiological result of the binding of the non-essential lanthanide and actinide metals to albumin, or transferrin, in the blood plasma may well be that the metals are held in a form in which they are virtually unable to penetrate the cell membrane in ionic form thus limiting cellular uptake and also the ability to cause harmful effects by interaction with essential enzymes or other proteins. Thus for the non-essential f elements, protein binding may be regarded as part of a protective mechanism against chemical toxicity,... 

The ultimate fate of plutonium that is not excreted promptly after administration or ingestion is deposition in the bone and other mineralized tissues. Whether the mineralization is phosphate- or carbonate-based appears to be immaterial. In cartilaginous fish, plutonium is concentrated in the skeleton to a significant extent, and in fish with a bony skeleton, the plutonium concentration in the soft tissues may be less than 1 % of that in the skeleton. The uptake of actinide elements from the body fluids by bone is a slow process, because of the strong binding of plutonium by transferrin. Autoradiography of bone shows quite different patterns of deposition for plutonium and ameridum compared to the deposition of radioactive caldum. Caldum deposition is uniform, whereas actinide deposition is irregular. The lack of uniformity in the distribution of the actinides deposited in bone may be related to variations in the pH of the bone surface, or to different concentrations of dtrate ion at different locations on the bone surface. 

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