Galactose and sialic acids function as if they are “recognition saccharides” on cell surfaces. However, does this kind of “feeling” have some scientific basis? Also, glycans are often described as if they are extremely diverse. However, we ordinarily deal with only some 10 monosaccharides and no more than several hundred glycans. Nevertheless, there has been no satisfactory explanation. Thus, we lack fundamental knowledge on saccharides. To understand the essence of glycans, the third bio-informative macromolecule, as well as nucleic acids and proteins, the time has come to face a very basic question, i. e., the origin of saccharides. In this chapter, the author attempts to answer this question through investigation of saccharide structures, classic glycochemical reactions, biosynthetic features of monosaccharides, and recognition proteins (lectins). As a consequence, a possible scenario on the origin of saccharides is presented. In the hypothesis, fructose, glucose and mannose are defined as the “first triplet” saccharides having been generated before the birth of life, whereas the others are characterized as “late-comer” saccharides as a result of the development of metabolism. The latter saccharides include galactose, xylose, L-arabinose, L-fucose, L-rhamnose, sialic acids, uronic acids, and even ribose. They can be regarded as “bricolage products” as a result of derivatization of the first triplet saccharides. Here, special emphasis is made that galactose, being one of “accepted aldohexoses” together with glucose and mannose because of their thermodynamic stability, has a clearly distinct “history” from that of glucose and mannose. This should have provided galactose with a unique character as a recognition saccharide.
In order to investigate the relationship between glycosyltransferase families and the motifs for them, we classified forty-seven glycosyltransferase families in the CAZy database into four superfamilies, GTS-A, -B, -C and -D, using a profile Hidden Markov Model method. On the basis of the classification and the similarity between GTS-A and nucleotidylyltransferase family catalyzing the synthesis of nucleotidesugar, we proposed that ancient oligosaccharide might have been synthesized by the origin of GTS-B whereas the origin of GTS-A might be the gene encoding for synthesis of nucleotidesugar as the donor and which have evolved to glycosyltransferases to catalyze the synthesis of divergent carbohydrates. We also suggested that the divergent evolution of each superfamily in the corresponding subcellular component has increased the complexities of eukaryotic carbohydrate structure.
Studies of glycoconjugates are now entering an era when their functional analysis in tissues is of primary importance. This information is vital for determining how these molecules contribute to disease, and how we might manipulate them to improve human health. Insights into glycoconjugate function are coming in some large measure from studies of the fruitfly Drosophila melanogaster. The complement of Drosophila glycoconjugates, their conservation with vertebrate glycans, together with the vast array of molecular and genetic tools available for studying this animal, make Drosophila a very powerful model organism for understanding the function of these diverse and functionally fascinating molecules. Developmental genetics allied with biochemical, structural, and molecular studies will provide for a complete understanding of glycoconjugates that can readily be applied to other systems and animals, including humans. A major challenge at present is understanding how glycoconjugates alter the activity of their protein or lipid acceptors in signaling and developmental patterning. Likewise, the cellular activities governed by glycans are only beginning to be described. For example, how do proteoglycans affect the levels of morphogens in the matrix? Do proteoglycans affect the stability, endocytosis, or diffusion of these critical patterning molecules? These issues can all be addressed with the tools available in Drosophila and the fruitlfly promises to remain a valuable tool in understanding glycoconjugate function in vivo.
Proteoglycans (PGs) are molecules found in abundance on the cell surface and in the extracellular matrix, and are involved in a variety of biological phenomena. Arecent analysis of Drosophila melanogaster mutants with defects in sulfotransferases revealed the significance of sulfation of Glycosaminoglycans (GAGs) on growth factor signaling during development. Sulfation of GAGs requires four steps: i) active transport of sulfate ion into the cells by sulfate transporters, ii) conversion into 3'-phosphoadenosine 5'-phosphosulfate (PAPS) by PAPS synthases, iii) translocation of PAPS from the cytosol into the Golgi apparatus by a PAPS transporter, and iv) transfer of sulfate from PAPS to GAGs by sulfotransferases. The com ponents of these steps are conserved among vertebrate and invertebrate animals. In this review, we summarize the significance of each step in providing PAPS prior to sulfotransferases, by comparing human and Drosophila genes.
Blood-group-ABH antigens have been attributed no physiological roles. While studying Ca2+ dependent cell-cell adhesion of Xenopus laevis, we found that blood-group-B active GPI-anchored lectin and blood-group-B active glycoconjugates are mediating cell adhesion of early embryonic cells. In mouse embryonic cells, not the blood-group-B antigens but the Lewis x blood-group-active molecules are playing similar roles in compaction. How did the surface glycomes playing roles in cell-cell adhesion evolve in these two species? In the nematode Caenorhabditis elegans, sugar chains of chondroitin proteoglycan play indispensable roles in completion of cell division. A decrease of chondroitin on the embryonic cell surfaces results in apparent reversion of cell division. Cytokinesis and chromosome partition becomes abnormal, and the embryonic cells die. Are chondroitin in the higher organisms playing similar roles in cell division, or are the roles of chondroitin replaced with different sugar chains? As seen in the two examples, comparison of glycomes between various organisms could be very powerful hypothesis generating tools in glycobiology. With the completion of genome DNA sequencing, it seems to be high time to study the evolution of glycomes with bioinformatics and functional glycomics.
Milk is the only food for the newborn young, and it contains many nutritious as well as biofunctional components which are available for the homeostasis and health of the immature newborn infants. People have been collecting the milk from several domestic animals such as cows, sheep, goats and horses in order to utilize them as raw foods or dairy products. Milk oligosaccharides, which are one of milk's components, have recently been recognized as significant anti-infectional compounds against pathogenic viruses and bacteria as well as being an energy source for the newborn young. They may also be materials which are required for the postnatal biosynthesis of glycoconjugates, particularly of the nervous system. It is concluded that the domestic animals' milk or colostrum are available to separate several biofunctional materials. Milk/colostrum of domestic animals, especially colostrum, contains large amounts of sialyl oligosaccharides as well as many kinds of neutral oligosaccharides. The colostrum should therefore be suitable as raw material for the large-scale preparation of milk oligosaccharides. Improved separation techniques will stimulate their utilisation in the pharmacological and food industries. Many types of oligosaccharides will also be used within an oligosaccharide library to help in determining the epitopes of several types of lectins or antibodies and clarifying the features of glycosyltransferases and glycosidases.