Defined in the narrowest sense, glycobiology is the study of the structure, biosynthesis, and biology of saccharides (sugar chains or glycans) that are widely distributed in nature. Sugars or saccharides are essential components of all living things and aspects of the various roles they play in biology are researched in various medical, biochemical and biotechnological fields.
According to Oxford English Dictionary the specific term glycobiology was coined in 1988 by Prof. Raymond Dwek to recognize the coming together of the traditional disciplines of carbohydrate chemistry and biochemistry. This coming together was as a result of a much greater understanding of the cellular and molecular biology of glycans. However as early as the late nineteenth century pioneering efforts were being made by Emil Fisher to establish the structure of some basic sugar molecules.
Sugars may be linked to other types of biological molecule to form glycoconjugates. The enzymatic process of glycosylation creates sugars/saccharides linked to themselves and to other molecules by the glycosidic bond, thereby producing glycans. Glycoproteins, proteoglycans and glycolipids are the most abundant glycoconjugates found in mammalian cells. They are found predominantly on the outer cell wall and in secreted fluids. Glycoconjugates have been shown to be important in cell-cell interactions due to the presence on the cell surface of various glycan binding receptors in addition to the glycoconjugates themselves.
Difficulties in the study of sugar structures
Part of the variability seen in saccharide structures is because monosaccharide units may be coupled to each other in many different ways, as opposed to the amino acids of proteins or the nucleotides in DNA, which are always coupled together in a standard fashion. The study of glycan structures is also complicated by the lack of a direct template for their biosynthesis, contrary to the case with proteins where their amino acid sequence is determined by their corresponding gene.
Glycans are secondary gene products and therefore are generated by the coordinated action of many enzymes in the subcellular compartments of a cell. Since the structure of a glycan may depend on the expression, activity and accessibility of the different biosynthetic enzymes, it is not possible to use recombinant DNA technology in order to produce large quantities of glycans for structural and functional studies as it is for proteins.
Modern tools and techniques for glycan structure prediction
Accurate machines and advanced software programs, when used in combination, can unlock the mystery of glycan structures. One such technique is Mass Spectrometry which uses three principal units: the ionizer, analyzer and detector. Fast Atom Bombardment (FAB) mass spectrometers are powerful tools for characterizing complex carbohydrates. This technique can be coupled with sensitive array detector technology.
Drugs already on the market, such as heparin, erythropoietin and a few anti-flu drugs have proven effective and highlight the importance of glycans as a new class of drug. Additionally, the search for new anti-cancer drugs is opening up new possibilities in glycobiology Anti-cancer drugs with new and varied action mechanisms together with anti-inflammatory and anti-infection drugs are today undergoing clinical trials. They may alleviate or complete current therapies. Although these glycans are molecules that are difficult to synthesize in a reproducible way, owing to their complex structure, this new field of research is highly encouraging for the future.
Glycobiology and skin
Glycobiology, in which recent developments have been made possible by the latest technological advances, helps provide a more specific and precise understanding of skin aging. It has now been clearly established that glycans are major constituents of the skin and play a decisive role in skin homeostasis.
- They play a crucial role in the recognition of molecules and cells, they act, most notably, at the surface of cells to deliver biological messages.
- They are instrumental in the metabolism of cells: synthesis, proliferation and differentiation
- They have a role to play in the structure and architecture of tissue.
Vital to the proper functioning of skin, glycans undergo both qualitative and quantitative changes in the course of aging. The functions of communication and metabolism are impaired and the skin’s architecture is degraded.
- Varki A, Cummings R, Esko J, Freeze H, Stanley P, Bertozzi C, Hart G, Etzler M (2008). "Essentials of glycobiology". Essentials of Glycobiology (Cold Spring Harbor Laboratory Press; 2nd edition). ISBN 0-87969-770-9.
- Varki A, Cummings R, Esko J, Freeze H, Hart G, Marth J (1999). "Essentials of glycobiology". Essentials of glycobiology (Cold Spring Harbor Laboratory Press). ISBN 0-87969-560-9.
- Rademacher TW, Parekh RB and Dwek RA. (1988). "Glycobiology". Annu. Rev. Biochem. 57 (1): 785–838. doi:10.1146/annurev.bi.57.070188.004033. PMID 3052290.
- Ma BY, Mikolajczak SA, Yoshida T, Yoshida R, Kelvin DJ, Ochi A (2004). "CD28 T cell costimulatory receptor function is negatively regulated by N-linked carbohydrates". Biochem. Biophys. Res. Commun. 317 (1): 60–7. doi:10.1016/j.bbrc.2004.03.012. PMID 15047148.
- Takahashi M, Tsuda T, Ikeda Y, Honke K, Taniguchi N (2004). "Role of N-glycans in growth factor signaling". Glycoconj. J. 20 (3): 207–12. doi:10.1023/B:GLYC.0000024252.63695.5c. PMID 15090734.
- Cold Spring Harbor Laboratory Press Essentials of Glycobiology, Second Edition
- Kreuger, J (2001). Decoding heparan sulfate. Retrieved 2008-01-11.
- Marth, JD (2008). "A unified vision of the building blocks of life". Nature Cell Biology 10 (9): 1015–6. doi:10.1038/ncb0908-1015. PMC 2892900. PMID 18758488.
- "Pohlmann, La glycobiologie, une nouvelle arme pour la médecine ?". 2007. Arte. ZDF. http://video.google.com/videoplay?docid=-7663079290156002221.
- Olden K, Bernard BA, Humphries M et al. (1985). Function of glycoprotein glycans T.I.B.S. pp. 78–82.
- Faury, G.,Ruszova,E.,Molinari,J.,Mariko,B.,Raveaud,S.,Velebny,V.,Robert,L. (2008). The alpha-1-rhamnose recognizing lectin site of human dermal fibrolasts functions as a signal transducer. Modulation of Ca++ fluxes and gene expression. Biochim.Biophys.Acta. pp. 1388–1394.
- Jang-Hee Oh, Yeon Kyung Kim, Ji-Yong Jung, Jeong-eun Shin, Jin Ho Chung (2011). Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo Experimental Dermatology.
- Glycoconjugates, Glycan Recognizing Proteins
- The Functional Glycomics Gateway. monthly updated web resource, a collaboration of Nature and the Consortium for Functional Glycomics.
- Carolyn Bertozzi's seminar: "Chemical Glycobiology"