Inhibition of polyisoprenoid and glycoprotein biosynthesis causes abnormal embryonic development.
Inhibition of polyisoprenoid and glycoprotein biosynthesis causes abnormal embryonic development.
复制标题
类异戊二烯和糖蛋白生物合成的抑制会导致胚胎发育异常。
DOI：
10.1073/pnas.76.11.5709
复制
发表时间：
1979
影响因子：
11.1
通讯作者：
W. Lennarz
中科院分区：
文献类型：
--
作者：
D. Carson;W. Lennarz
紧缩素是一种有效的类异戊二烯生物合成抑制剂，在对早期胚胎发育或大分子合成没有影响的浓度下，会诱导海胆发育过程中的异常原肠形成。三条证据表明，致密素引起的发育损害是由于抑制了二羟苯乙醇的生物合成，以及伴随而来的N-连接糖蛋白的寡糖链的生物合成的抑制。(I)在紧缩素存在的情况下培养的胚胎在单独补充二羟胆碱的情况下正常原肠形成，而补充胆固醇或辅酶Q或两者都不能阻止紧缩素诱导的发育损害。(Ii)将外源添加的[~3H]二羟苯二酚并入具有低聚糖-焦磷酰二醇层析性质的化合物中。(Iii)在致密蛋白存在的情况下培养的胚胎合成甘露糖标记的糖脂和N-连接糖蛋白的能力降低。如果胚胎与紧缩素一起培养，这种合成的减少就会消失。
Compactin, a potent inhibitor of polyisoprenoid biosynthesis, induces abnormal gastrulation during sea urchin development at concentrations that have no effect on earlier embryonic development or on macromolecular synthesis. Three lines of evidence suggest that the developmental lesion caused by compactin results from inhibition of dolichol biosynthesis and a concomitant inhibition in the biosynthesis of the oligosaccharide chains of N-linked glycoproteins. (i) Embryos cultured in the presence of compactin gastrulate normally when supplemented with dolichol alone, whereas supplementation with cholesterol or coenzyme Q or both does not prevent the compactin-induced developmental lesion. (ii) Exogenously supplemented [3H]dolichol is incorporated into a compound with the chromatographic properties of oligosaccharide-pyrophosphoryldolichol. (iii) Embryos cultured in the presence of compactin exhibit a decreased capacity to synthesize mannose-labeled glycolipids and N-linked glycoproteins. This decrease in synthesis is abolished if the embryos are cultured in the presence of dolichol along with compactin.