糖鎖の成り立ちから糖の起源を推理する

抄録

Glycans are carbohydrate chains that are considered to be one of the most essential bio-informative macromolecules as well as nucleic acids and proteins. Although biological significance and actual states of glycans are not yet fully understood, they certainly play fundamental roles in various recognition phenomena, such as microbe-parasite infections, cell proliferation and differentiation, fertilization, apoptosis, cancer metastasis, etc. Distinct from nucleic acids, glycans are expressed on cell surfaces and in extracellular matrices as various forms of glycoconjugates. They are indispensable to cover vital cells and to protect against physical and biochemical attacks. Distinct from proteins, glycans are indirect products of so-called glycogenes, i.e., genes that encode glycosyltransfearses, glycosidases and sugar nucleotide transporters involved in glycan biosynthesis. Since individual steps of these processes are not complete, a series of glycans are produced simultaneously as a consequence of collaboration of glycogenes. Here, a"multi genes-multi glycans" principle is applied for glycan biosynthesis instead of the "one gene-one enzyme" principle for nucleic acids and proteins.. As another unique feature of glycans, they have a number of linkage and branching isomers. Nevertheless, sugar units, e.g., glucose (C₆H₁₂O₆), are extremely simple in their compositions, reflecting formal name, "carbohydrates", which mean "C + H₂O". In addition, only carbohydrates lack nitrogen, whereas amino acids and nucleotides contain this atom. On the other hand, saccharides have chirality like amino acids. Naturally occurring saccharides are basically defined as "D-enantiomers", while L-fucose, L-rhamnose and some other L-sugars are actually biosynthesized from either D-mannose or D-glucose. Important notation is that only few component saccharides, i.e., D-glucose, D-mannose and D-galactose are utilized in nature among possible 16 aldohexoses. This observation implies that the first living organisms could make use of a relatively small number of simple saccharides that had been sufficiently available on the prebiotic earth. In this article, the author reviews structural and metabolic features of naturally occurring saccharides and classic glycochemistries. Hence, he presents a possible scenario on the origin of saccharides consisting of i) formose reaction to generate the smallest (C3) sugars, ii) aldol condensation between glyceraldehyde (GA) and dihydroxyacetone (DHA) to yield few ketohexoses, and iii) Lobry de Bruyn rearrangement to convert fructose into glucose. The scenario clearly explains how and why only a few elementary saccharides were born and selected. On the other hand, galactose is categorized into "late-comer" saccharides together with many other "bricolage" saccharides, such as ribose, sialic acid and more unusual deoxy- and dideoxyaldohexoses. In the end, the author refers to the essence of "glycome project", which is an emerging field of glycobiology along with the concept of post-genome science.