Hempe J M, Cousins R J
Center for Nutritional Sciences, University of Florida, Gainesville 32611.
J Nutr. 1992 Jan;122(1):89-95. doi: 10.1093/jn/122.1.89.
Dietary zinc may regulate zinc absorption in part via the inhibitory effect of intestinal metallothionein, but the mechanism is unknown. We recently showed that cysteine-rich intestinal protein (CRIP) binds zinc during transmucosal zinc transport, and that CRIP may function as an intracellular zinc carrier. The present experiments examine the interaction of CRIP and metallothionein with zinc to evaluate their potential roles in the mechanism of zinc absorption. Intestinal metallothionein concentrations were lower and zinc absorption rates from isolated intestinal loops were higher in rats fed a low zinc diet compared with those fed a high zinc diet or given parenteral zinc to induce metallothionein synthesis. Zinc status did not affect the apparent CRIP concentration, but markedly altered the distribution of 65Zn in intestinal cytosol as determined by gel filtration HPLC. More 65Zn was associated with CRIP (40 vs. 14%) and less was bound to metallothionein (4 vs. 52-59%) in rats fed the low zinc diet compared with rats of high zinc status. Luminal zinc concentration also affected the distribution of 65Zn in the cytosol. CRIP bound progressively less (from 42 to 25%) of the 65Zn taken up from the lumen as the luminal zinc concentration was increased from 5 to 300 mumol/L. Collectively these data suggest that CRIP is a saturable, intracellular zinc transport protein, and that metallothionein inhibits zinc absorption by binding zinc in competition with CRIP. A hypothetical model for the mechanism of transcellular zinc absorption involving metallothionein and CRIP is presented and discussed.
膳食锌可能部分通过肠道金属硫蛋白的抑制作用来调节锌的吸收，但其机制尚不清楚。我们最近发现，富含半胱氨酸的肠蛋白（CRIP）在跨粘膜锌转运过程中与锌结合，并且CRIP可能作为细胞内锌载体发挥作用。本实验研究了CRIP和金属硫蛋白与锌的相互作用，以评估它们在锌吸收机制中的潜在作用。与喂食高锌饮食或给予肠外锌以诱导金属硫蛋白合成的大鼠相比，喂食低锌饮食的大鼠肠道金属硫蛋白浓度较低，离体肠袢的锌吸收率较高。锌状态不影响CRIP的表观浓度，但通过凝胶过滤高效液相色谱法测定，显著改变了肠道细胞溶质中65Zn的分布。与高锌状态的大鼠相比，喂食低锌饮食的大鼠中更多的65Zn与CRIP相关（40%对14%），而与金属硫蛋白结合的较少（4%对52 - 59%）。肠腔锌浓度也影响细胞溶质中65Zn的分布。随着肠腔锌浓度从5μmol/L增加到300μmol/L，CRIP结合从肠腔摄取的65Zn的比例逐渐减少（从42%降至25%）。这些数据共同表明，CRIP是一种可饱和的细胞内锌转运蛋白，并且金属硫蛋白通过与CRIP竞争结合锌来抑制锌吸收。本文提出并讨论了一个涉及金属硫蛋白和CRIP的跨细胞锌吸收机制的假设模型。
