Transferrin transition metals

Trans effect, 543-545 Transferrins, 937 Transition metal hydrides, acidities of. 643... 

Box 12-F), which tends to occupy a fraction of the transferrin sites in blood, although it binds much more weakly than does Fe. Several other binding sites for transition metals are pictured in Chapter 16. 

Although both GPx and Cat are very efficient in removing H202, HO can still be formed in abundance (Fenton and Haber-Weiss chemistry). To partially offset the influence of transition metal ions on free radical production, there are numerous metal-binding proteins which prevent these reactions from taking place these include, among others, ferritin, transferrin, ceruloplasmin, and metallotheinein (Table 2). 

Most of the divalent transition metal ions bind only weakly to transferrins, the binding constants for Fe2+, Ni2+, and Zn2+ being approximately 103, 104, and 105, respectively (Table VII). Cu2+ may be an exception. Although no binding constants have been determined for any of its complexes with transferrins, and metal displacement studies indicate that it binds less strongly than Al3+ (144) and Mn3+ (154), it does form a very stable complex and has been used more than any other metal ion (apart from Fe3+) for physicochemical studies on transferrins. With its d9 electron configuration, Cu2+ has, like V02+, provided an excellent and much-used EPR probe of transferrin structure. It was the EPR spectra of Cu2+-transferrin (91), -ovotransferrin (157), and -lactoferrin (92) complexes that provided the most compelling evidence... 

The transferrins are iron chelating agents found in the various fluids of vertebrates including humans (2). They are powerful iron chelators with binding constants for ferric iron of >K 30—31. They have molecular weights up to about 80,000 and two iron binding sites per molecule. Other transition metals can occupy the two iron sites although iron will displace them. 

Enzyme-bound transition metals usually catalyze nontoxic oxidations and iron in the storage form is usually bound as Fe, but reducing agents may convert bound iron to Fe " " causing its release, whereby it becomes reactive (B6, C4, W5). Free cellular iron may reside in a labile chelatable pool (Kl). This pool appears to be regulated by cytoplasmic iron regulatory proteins that modulate production of transferrin and ferritin (C4). Increases in this pool may facilitate oxidation (Kl). One of the seven coppers in the acute phase protein ceruloplasmin can catalyze the oxidation of lipoproteins as readily as free copper, and hence is a potentially important physiological prooxidant (F2, M9). 

Lactoferrin is an iron transport non-heme glycoprotein present in human milk and many biological secretions that can effectively inhibit the oxidation of various lipid systems by its iron-binding capacity. However, this protein can also have prooxidant activity, depending on the lipid system, and its concentration relative to the concentration of metal ions. Lactoferrin effectively inhibited oxidation and increased the oxidative stability of infant formulas supplemented with iron (see Chapter ll.C). Other known proteins that chelate or inactivate transition metals are found in biological systems including transferrin, albumin, and ceruloplasmin (Chapter 13). 

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