Subsidence of venice: predictive difficulties.

in equilibrium with metallothionein at pH 7.4 after 48 hours. We are currently reexamining copper binding to normal metallothionein and metallothionein from subjects with hepatolenticular degeneration under different experimental conditions. If, as Scheinberg suggests, copper is bound to metallothionein in the cuprous form, our interpretation of the data is indeed incorrect, and I will take full responsibility for dubious experimental design and incorrect interpretation of results. However, before submitting to Scheinberg's refutation, I would like to see experimental evidence proving that copper is bound in the cuprous form. Scheinberg has stated that "it is almost certain that copper is bound as cuprous ions . . ." (italics mine) and referenced experiments demonstrating that copper is reduced by thiols. Scheinberg has overlooked the fact that we are dealing with a unique protein-a protein in which an average of three cysteinyl residues are involved in the binding of each metal atom (2). A complex involving three sulfhydryl groups, possibly another electron-pair donor, and a cupric ion would preclude oxidation-reduction and permit equilibrium to be obtained in a solution containing cupric ion. Indeed, cupric complexes with two cysteine molecules have been described (3). Thus, the presence of a thiol and a cupric ion does not necessarily dictate oxidation-reduction. G. W. EVANS Human Nutrition Laboratory, Agricultural Research Service, Grand Forks, North Dakota 58201