History of Sialic Acids, Gangliosides, and GM3

Abstract

Ganglioside was first named by the German scientist Ernst Klenk in 1942 since he for the first time identified it as lipids from ganglion cells of the brain [1]. By 2011, 188 gangliosides are classified in vertebrate alone. For 70 years since the first naming of ganglioside by Klenk, globular acknowledgments have been accumulated on the GM3. In 1951, the sialic acid as a form of sialic acid-containing substance was first found at cell surface membranes of dried ghosts from horse erythrocytes and the isolated acidic sugar compound named hematoside, nowadays GM3 [2, 3]. During the isolation, the dried membranes of packed horse erythrocytes were treated with diethyl ether-methanol (1:1) to extract substances and then further extracted with chloroform-methanol (1:1). The prepared substance was examined to react with reagent orcinol, which is used as the authentic neuraminic acid (sialic acid)-reactive reagent. He, for the first time, called this glycolipid isolated from horse erythrocytes as hematoside in order to distinguish this glycolipid hematoside from the ganglioside isolated by Klenk’s preceding report. However, in fact, the hematoside is GM3 [4]. The hematoside isolated by Yamakawa constituted of an acidic sugar without detailed structural basis but named hemataminic acid that showed a purple color upon orcinol reaction. Thus, his hemataminic acid was also a family of neuraminic acid, what Klenk had earlier discovered them from horse species [1]. In early 1935, Klenk had prepared and isolated an orcinol-reacting purple-colored substance from the brain tissues of human patients of specific lysosomal storage disease, Niemann–Pick diseases [5, 6]. In 1942, Klenk designated this substance, purple-colored substance, to ganglioside [1] because the isolated substances occupied in very high concentration level in neuronal tissue, ganglions. After treatment and incubation of the isolated substances of gangliosides with methanolic hydrochloric acid, crystalline substance with the orcinol-reacted purple color was precipitated, and they named neuraminic acid [7]. In earlier 1936, a scientist Blix isolated polyhydroxyamino acid-like substances from submaxillary mucins of bovine. Thereafter, in 1952, he named it sialic acid as different designation [8]. In another side, a biochemist, R. Kuhn isolated lactaminic acid from cow colostrum [9]. Now, the orcinol-responded substances with the four different names of lactaminic acid, hemataminic acid, sialic acid, and neuraminic acid meant the same sugar. The conclusive description of the name has been summarized by a biochemist, A. Gottschalk in Australia [10, 11]. Now, it is well-known that the simple GM3 ganglioside is abundantly occupied in mammalian cell plasma membrane (PM). In addition, the GM3 has been documented for the functional roles of GM3 in migration, proliferation, senescence, and apoptosis. Genetic mutant mice in ganglioside synthesis, including GM3, have been established with some preventive and therapeutic targets.