Zinc transport by fibroblasts from patients with acrodermatitis enteropathica

Abstract

Acrodermatitis enteropathica (AE) is a zinc deficiency disease. To date, the only defect has been demonstrated in the gut. We have investigated zinc uptake in fibroblasts established from four unrelated patients with AE using normal skin fibroblasts as controls. Zinc content of AE and control cells was similar (0.3 fmol/cell). Zinc accumulation over 24 h from a complete culture medium was similar in both normal controls and mutant cells. The fraction of zinc removed by Pronase treatment remained constant at 50 pmol/micrograms DNA, whereas the zinc remaining after Pronase treatment accumulated rapidly for 8 h, then more slowly. Analysis of binding data showed no significant difference between AE and control cells, with apparent Ka values of 4-6 X 10(6) M-1 and between 1 and 2 X 10(8) receptors/cell. Analysis of Pronase resistant data showed no difference between the control and the mutant cells with apparent Km values of 0.2-0.3 microM and Vmax values of 17-19 pmol/micrograms DNA/h. No difference in zinc efflux rates was detected. We conclude that the defect that underlies acrodermatitis enteropathica is either not expressed in fibroblasts or cannot be detected under these experimental conditions.