The acrodermatitis enteropathica mutation transiently affects zinc metabolism in human fibroblasts.

The acrodermatitis enteropathica (AE) mutation has been shown to affect zinc transport in human intestinal biopsies. However, whether the mutation is also expressed in human fibroblasts has not been determined. The activity of the zinc-dependent enzyme, 5' nucleotidase, and cell zinc content were measured in normal and AE fibroblasts 2 and 4 d after subculturing to determine the effect of the AE mutation on zinc metabolism. The activity of 5' nucleotidase in AE cells was 68% of normal at 2 d after subculturing. Although 5' nucleotidase activity had decreased significantly in both normal and AE fibroblasts at 4 d after subculturing, there was no significant difference between the two genotypes. The zinc content of AE fibroblasts was also significantly reduced. Acrodermatitis enteropathica fibroblasts contained 62% less zinc than normal fibroblasts at 2 d. By 4 d the normal fibroblast zinc content had decreased to that of the AE fibroblasts. The uptake and transport of 65Zn into AE fibroblasts at 2 d was measured because these cells exhibited reduced 5' nucleotidase activity and cell zinc content at this time. The uptake of zinc over a 90-min time period was the same in the two genotypes. However, AE fibroblasts incubated with 2-10 mumol Zn/L for 15 min had significantly slower zinc transport compared with normal fibroblasts. In both genotypes, Michaelis-Menten kinetics were observed. Normal and AE fibroblasts had similar affinities for zinc (Km), but AE fibroblasts exhibited a Vmax which was reduced by 38%. These results indicate that the phenotypic expression of the AE mutation occurs in a time-dependent manner, is not restricted to the intestine and is also transiently expressed in human fibroblasts, resulting in abnormal zinc metabolism in these cells.