Muchmore E A, Diaz S, Varki A
UCSD Cancer Center, Division of Hematology-Oncology, University of California San Diego, La Jolla 92093-0687, USA.
Am J Phys Anthropol. 1998 Oct;107(2):187-98. doi: 10.1002/(SICI)1096-8644(199810)107:2<187::AID-AJPA5>3.0.CO;2-S.
The sialic acids are major components of the cell surfaces of animals of the deuterostome lineage. Earlier studies suggested that humans may not express N-glycolyl-neuraminic acid (Neu5Gc), a hydroxylated form of the common sialic acid N-acetyl-neuraminic acid (Neu5Ac). We find that while Neu5Gc is essentially undetectable on human plasma proteins and erythrocytes, it is a major component in all the four extant great apes (chimpanzee, bonobo, gorilla and orangutan) as well as in many other mammals. This marked difference is also seen amongst cultured lymphoblastoid cells from humans and great apes, as well as in a variety of other tissues compared between humans and chimpanzees, including the cerebral cortex and the cerebrospinal fluid. Biosynthetically, Neu5Gc arises from the action of a hydroxylase that converts the nucleotide donor CMP-Neu5Ac to CMP-Neu5Gc. This enzymatic activity is present in chimpanzee cells, but not in human cells. However, traces of Neu5Gc occur in some human tissues, and others have reported expression of Neu5Gc in human cancers and fetal tissues. Thus, the enzymatic capacity to express Neu5Gc appears to have been suppressed sometime after the great ape-hominid divergence. As terminal structures on cell surfaces, sialic acids are involved in intercellular cross-talk involving specific vertebrate lectins, as well as in microbe-host recognition involving a wide variety of pathogens. The level of sialic acid hydroxylation (level of Neu5Ac versus Neu5Gc) is known to positively or negatively affect several of these endogenous and exogenous interactions. Thus, there are potential functional consequences of this widespread structural change in humans affecting the surfaces of cells throughout the body.
唾液酸是后口动物谱系动物细胞表面的主要成分。早期研究表明，人类可能不表达N-羟乙酰神经氨酸（Neu5Gc），这是常见唾液酸N-乙酰神经氨酸（Neu5Ac）的一种羟基化形式。我们发现，虽然在人血浆蛋白和红细胞上基本检测不到Neu5Gc，但它是所有现存的四种大型猿类（黑猩猩、倭黑猩猩、大猩猩和猩猩）以及许多其他哺乳动物中的主要成分。在人类和大型猿类的培养淋巴母细胞中，以及在人类和黑猩猩之间比较的各种其他组织中，包括大脑皮层和脑脊液中，也可以看到这种显著差异。从生物合成角度来看，Neu5Gc是由一种羟化酶作用产生的，该酶将核苷酸供体CMP-Neu5Ac转化为CMP-Neu5Gc。这种酶活性存在于黑猩猩细胞中，但不存在于人类细胞中。然而，在一些人类组织中存在痕量的Neu5Gc，并且其他人报道了Neu5Gc在人类癌症和胎儿组织中的表达。因此，表达Neu5Gc的酶能力似乎在大型猿类与原始人类分化后的某个时候受到了抑制。作为细胞表面的末端结构，唾液酸参与涉及特定脊椎动物凝集素的细胞间相互作用，以及涉及多种病原体的微生物-宿主识别。已知唾液酸羟基化水平（Neu5Ac与Neu5Gc的水平）对这些内源性和外源性相互作用中的几种有正向或负向影响。因此，人类这种影响全身细胞表面的广泛结构变化存在潜在的功能后果。
