Characterization and developmental expression of lactotriosylceramide:galactosyltransferase for the synthesis of neolactotetraosylceramide in the nervous system.
Characterization and developmental expression of lactotriosylceramide:galactosyltransferase for the synthesis of neolactotetraosylceramide in the nervous system.
复制标题
乳三糖神经酰胺的表征和发育表达：用于神经系统中新乳四糖神经酰胺合成的半乳糖基转移酶。
DOI：
10.1046/j.1471-4159.1994.62010307.x
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发表时间：
1994
影响因子：
4.7
通讯作者：
Jungalwala,FB
中科院分区：
文献类型：
--
作者：
Chou,DK;Jungalwala,FB
新乳糖脂衍生自新乳糖四糖基神经酰胺（nLcOse 4Cer）。它们在胚胎和新生儿发育期间在大鼠大脑皮质中发现，并在出生后不久消失。然而，这些糖脂在成人小脑中是丰富的。乳三糖神经酰胺（LcOse 3Cer）：在哺乳动物脑中表征了半乳糖基转移酶（GT），其催化nLcOse 4Cer生物合成的终末步骤。该酶对LcOse 3Cer具有高度特异性，末端有一个GlcNAcβ1 - 3Gal-残基，并且不催化半乳糖转移到其他糖脂中，研究了其他糖脂的替代碳水化合物残基。微粒体膜酶需要Mn 2+和去污剂的体外活性。最适pH为7.4，Km值为34 μM（Vmax= 0.2nmol/mg/h）。LcOse 3Cer：GT与GM 2：GT和可溶性乳糖合成酶A不同。LcOse 3 Cer：GT的比活性在年轻成年大鼠脑的白色物质中比在灰质中高5倍，而GM 2：GT在白色物质中仅高约1.5倍。LcOse 3Cer：GT在大脑皮质和小脑的发育性表达与nLcOse 4Cer在这些神经区域的表达水平无相关性。尽管完全没有nLcOse 4Cer在5天以上的动物的大脑皮层中，显着的LcOse 3Cer：GT的活动，发现即使在成年人的皮层。在小脑中，nLcOse 4Cer的水平随着发育而增加，但该酶的比活性在出生后不久降低了50%，然后随着发育几乎保持不变。结果表明，LcOse 3Cer：GT不是控制脑中nLcOse 4Cer及其衍生的新乳糖脂表达的调节酶。
Neolactoglycolipids are derived from neolactotetraosylceramide (nLcOse4Cer). They are found during the embryonic and neonatal developmental periods in the rat cerebral cortex and disappear shortly after birth. These glycolipids are, however, abundant in the adult cerebellum. Lactotriosylceramide (LcOse3Cer):galactosyltrans‐ ferase (GT), which catalyzes the terminal step in the biosynthesis of nLcOse4Cer, was characterized in mammalian brain. The enzyme was highly specific for LcOse3Cer, with a terminal GlcNAcβ1 ‐3Gal‐residue, and it did not catalyze the transfer of galactose to other glycolipids studied with alternate carbohydrate residues. The microsomal membrane enzyme required Mn2+and a detergent for in vitro activity. The optimal pH was 7.4, and theKmvalue for LcOse3Cer was 34 μM(Vmax=∼2 nmol/mg/h). The LcOse3Cer:GT was shown to be different from the GM2:GT and the soluble enzyme lactose synthase A. The specific activity of LcOse3Cer:GT was enriched fivefold higher in the white matter than in the gray matter of young adult rat brain, whereas GM2:GT was enriched only about 1.5‐fold higher in the white matter. The developmental expression of LcOse3Cer:GT in the cerebral cortex and cerebellum was not correlative with the levels of nLcOse4Cer in these neural areas. Despite the complete absence of nLcOse4Cer in the cerebral cortex of animals older than 5 days, significant activity of the LcOse3Cer:GT was found even in the adult cortex. In cerebellum, the levels of nLcOse4Cer increased with development, but the specific activity of the enzyme was reduced by 50% soon after birth and then remained practically the same with development. The results indicate that LcOse3Cer:GT is not a regulatory enzyme that controls the expression of nLcOse4Cer and its derived neolactoglycolipids in the brain.