Movement of zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts.
Movement of zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts.
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DOI：
10.1016/s0021-9258(18)54658-5
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发表时间：
1991-11
期刊：
影响因子：
--
通讯作者：
Y. Lange;F. Echevarria;T. Steck
中科院分区：
文献类型：
--
作者：
Y. Lange;F. Echevarria;T. Steck
胆固醇在内质网中合成，而其前体酵母甾醇主要存在于质膜中。这些不同的发现的新含义是，酵母甾醇在细胞内循环。在跟踪其运动，我们现在已经建立了以下：（a）在人类成纤维细胞，酵母甾醇转化为胆固醇，只有在粗糙的ER。(b)很少或没有酵母甾醇或胆固醇在体内粗面内质网中积累。(c)新合成的酵母甾醇移动到质膜没有可检测到的滞后，半衰期为9分钟，大约是胆固醇的两倍。(d)质膜中的放射性标记的酵母甾醇库迅速翻转，比细胞内胆固醇翻转得更快。因此，质膜酵母甾醇不是停滞的。(e)脉冲进入完整细胞的[3H]发酵甾醇最初存在于质膜中。它被迅速内化，然后转化为[3H]胆固醇。产生的一半[3H]胆固醇在初始[3H]酵母甾醇脉冲的30分钟内返回到质膜。(f)新生酵母甾醇在到达质膜之前积累在富含甾醇的漂浮细胞内膜中。该膜还获得新生胆固醇、脉冲进入完整细胞的外源[3H]酵母甾醇和由外源[3H]酵母甾醇合成的[3H]胆固醇。这些结果表明，至少有一种甾醇移动迅速，并在两个方向之间的粗面内质网，富含甾醇的细胞内膜轴承新生胆固醇，和质膜。
Where examined, cholesterol is synthesized in the endoplasmic reticulum; however, its precursor, zymosterol, is found mostly in the plasma membrane. The novel implication of these disparate findings is that zymosterol circulates within the cell. In tracing its movements, we have now established the following: (a) in human fibroblasts, zymosterol is converted to cholesterol solely in the rough ER. (b) Little or no zymosterol or cholesterol accumulates in the rough ER in vivo. (c) Newly synthesized zymosterol moves to the plasma membrane without a detectable lag and with a half-time of 9 min, about twice as fast as cholesterol. (d) The pool of radiolabeled zymosterol in the plasma membrane turns over rapidly, faster than does intracellular cholesterol. Thus, plasma membrane zymosterol is not stagnant. (e) [3H]Zymosterol pulsed into intact cells is initially found in the plasma membrane. It is rapidly internalized and is then converted to [3H] cholesterol. Half of the [3H]cholesterol produced returns to the plasma membrane within 30 min of the initial [3H]zymosterol pulse. (f) Nascent zymosterol accumulates in a buoyant sterol-rich intracellular membrane before it reaches the plasma membrane. This membrane also acquires nascent cholesterol, exogenous [3H]zymosterol pulsed into intact cells, and [3H]cholesterol synthesized from the exogenous [3H] zymosterol. These results suggest that at least one sterol moves rapidly and in both directions among the rough endoplasmic reticulum, a sterol-rich intracellular membrane bearing nascent cholesterol, and the plasma membrane.