Fucolipids (1978)

Fucolipids are complex glycosphingolipids found in human erythrocytes and in certain secretory tissues of several mammalian species.They are of special interest because of their antigenic activity in the A B 0 and Lewis blood group systems and are mainly responsible for this activity in human blood.Although antigenicity was earlier recognized in glycolipid preparations of red blood cells ( 1, 2), fucose was not identified as a component sugar of glycolipids until 1963 (3, 4).It was not specifically associated with the blood groupactive glycolipids until Yamakawa, Nishimura, and Kamimura (5) reported the separation of two glycolipids that were immunologically active and relatively rich in fucose.The first pure fucolipid was isolated from human gastric adenocarcinoma and human bronchogenic carcinoma tissue by Hakomori and Jeanloz in 1964 (6).Since this time much has been discovered about the chemistry and biology of these substances.Research has been stimulated by interest in the immunology of biohaptens that could be obtained in pure form, by interest in cell membrane chemotopography, and by the role of membrane components in normal cell and in tumor cell biology.This review will consider briefly the chemical nature, the methods and techniques for isolation and identification, the biosynthesis, and some aspects of the biology of the fucolipids.Several excellent reviews are available on subjects involving fucolipids: one on blood group antigens by Hakomori and Kobata (7), one on blood group glycolipids in normal and tumor tissue by Hakomori (8), and one on glycolipids of tumor cell membranes by Hakomori (9).The reader is also referred to a general review of the biochemistry of glycosphingolipids by Wiegandt (10).A 1975 symposium on glycolipids, Glycolipid Methodology, has been published in book form by the American Oil Chemists' Society Press (1 l), and Volume 28 part B of Methods in Enzymology contains many valuable references relating to the complex glycolipids and fucolipids (1 2). I. NATURE OF THE FUCOLIPIDSAll of the fucolipids thus far isolated are ceramide oligosaccharides containing five or more sugars, with the single exception of a fucosyl ceramide (13).Besides the fucose, one glucose, two or more galactoses, and N-acetylglucosamine are usually present, and N - acetylgalactosamine is present in the fucolipids with blood group A-activity.Only two types of fucolipids containing sialic acid have been reported.All of the sugars are in glycosyl linkage in the pyranosyl form and all are of the D series except fucose.Most of the known fucolipids are glycosyl derivatives of lacto-N-tetraosyl ceramide or lacto-N-neotetraosyl ceramide, giving rise to the "type 1" and "type 2" (14) oligosaccharide chains, respectively.Lacto-N-tetraosylceramide; Type 1 chain Gal(P1 + 3)GlcNAc(Pl + 3)Gal(Pl + 4)Glc(P1 + 1)ceramide Lacto-N-neotetraosylceramide, or "paragloboside"; Gal@ 1 + 4)GlcNAc(P 1 + 3)Gal(P 1 + 4)Glc(P 1 Type 2 chain + 1) ceramide Substitution of fucose, galactose, and N-acetylgalactosamine residues at the appropriate positions of these precursors gives rise to all of the A B 0 and Lewis blood group antigens of the simplest kind.A few examples of these are given in Table 1 and the complete structure of one is shown in Fig. 1.There are a number of variants that include an extra galactose in the precursor chain or deletion of the N-acetylglucosamine.Several larger fucolipids contain a -Gal(Pl + 4)-GlcNAc(P 1 + 3)-disaccharide inserted between the