A sialic acid-specific O-acetylesterase in human erythrocytes: possible identity with esterase D, the genetic marker of retinoblastomas and Wilson disease.

A sialic acid-specific O-acetylesterase in human erythrocytes: possible identity with esterase D, the genetic marker of retinoblastomas and Wilson disease.
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DOI:
10.1073/pnas.83.4.882
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发表时间:
1986-02
影响因子:
11.1
通讯作者:
A. Varki;E. Muchmore;S. Diaz
A. Varki;E. Muchmore;S. Diaz
中科院分区:
综合性期刊1区
文献类型:
--
作者:
A. Varki;E. Muchmore;S. Diaz

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“非特异性”酯酶是一类酶,最初被识别是因为它们与合成的O-乙酰酯底物发生反应。虽然这些酶的电泳多态性对遗传学研究非常有用,但它们的生物学功能仍然完全未知。酯酶D的特征是它与4-甲基伞形花序乙酸酯的反应活性。这种酶最近引起了人们的特别兴趣,因为它与可能导致视网膜母细胞瘤的隐性基因和导致威尔逊病的隐性基因紧密连锁。我们在这里描述了一种人红细胞酯酶的部分纯化,该酶似乎对O-乙酰化唾液酸具有高度专一性。接下来,我们提出的证据表明,酯酶D与这种唾液酸特异性O-乙酰酯酶相同。首先,这两种活性都是通过几个不同的纯化步骤从人的红细胞裂解物中分离出来的,每个步骤都使用不同的分离原理。其次,这两种活性在各种不同的试剂中表现出非常相似的抑制曲线。第三,它们都显示出几乎相同的热失活曲线。这种胞浆唾液酸特异性O-乙酰基酯酶似乎参与了O-乙酰化唾液酸分子的“循环”。因此,酯酶D可能是第一个可以预测其特定生物学作用的非特异性酯酶。
The "nonspecific" esterases are a family of enzymes that were originally identified because of their reaction with synthetic O-acetyl ester substrates. While the electrophoretic polymorphisms of these enzymes have been extremely useful for genetic studies, their biological functions have remained completely unknown. Esterase D is characterized by its reactivity with 4-methylumbelliferyl acetate. This enzyme has recently been of particular interest because of its tight linkage to the putative recessive gene causing retinoblastomas, and to the recessive gene causing Wilson disease. We describe here the partial purification of a human erythrocyte esterase that appears to be highly specific for O-acetylated sialic acids. We next present evidence that suggests that esterase D is identical to this sialic acid-specific O-acetylesterase. First, both activities copurify from human erythrocyte lysates through several different purification steps, each of which use different principles of separation. Second, both activities show a remarkably similar profile of inhibition with a variety of different agents. Third, they both show a nearly identical heat-inactivation profile. This cytosolic sialic acid-specific O-acetylesterase appears to be involved in the "recycling" of O-acetylated sialic acid molecules. Thus, esterase D may be the first nonspecific esterase for which a specific biological role can be predicted.