Glutathione cadmium complexes

Ions of several metals such as zinc, cadmium, lead, nickel, and mercury form very stable complexes with glutathione, disturb the interconversion of oxidised reduced glutathione, which results in a lowering of the level of available antioxidants in cells (Christie and Costa, 1984). 

Fuhr, B.J., Rabenstein, D.L., 1973. Nuclear magnetic resonance studies of the solution chemistry of metal complexes. IX. The binding of cadmium, zinc, lead and mercury by glutathione. J. Am. Chem. Soc. 95, 6944-6950. 

A further complication in the identification of target sites and chemical forms of metals is the kinetic lability of coordinate covalent bonds. Metal ligands exchange rapidly in and out of the coordination sphere, in particular for first-row transition metals. This kinetic lability varies between metals, and, as indicated above, is influenced by the nature of the ligand, whether mono- or multidentate, and by the pH and ionic strength of its immediate environment. Copper, for example, forms relatively low affinity complexes with albumin or amino acids, but is tightly bound to ceruloplasmin. Similarly, mercury and cadmium form kinetically labile complexes with amino acids, glutathione, or albumin, but more stable chelates with metallothionein. 

Apart from glutathione, AlaAlaCys is the only tripeptide the cadmium(II) complexes of which have been studied [94]. Interestingly, its complex formation processes are very similar to those of AlaCys, the (S ,COO -coordinated C-terminus being the exclusive cadmium(II) binding site. This is a significant difference to the complex formation of any other peptide because in the absence of cysteinyl residues the N-terminal amino acids are the primary metal binding sites. 

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