Glycobiology

For the journal, see Glycobiology (journal).

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.[1][2] 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.

History

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.[3] 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.

Glycoconjugates

Main articles: Glycoconjugates and Glycosylation

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.[4][5] In addition to their function in protein folding and cellular attachment, the N-liked glycans of a protein can modulate the protein's function, in some cases acting as an on-off switch.[6]

Glycomics

Main article: Glycomics

"Glycomics, analogous to genomics and proteomics, is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology.[7]

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.[8] 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.[9]

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.

Multiple Reaction Monitoring (MRM)

MRM is a mass spectrometry-based technique that has recently been used for site-specific glyosylation profiling. Although MRM has been used extensively in metabolomics and proteomics, its high sensitivity and linear response over a wide dynamic range make it especially suited for glycan biomarker research and discovery. MRM is performed on a triple quadrupole (QqQ) instrument, which is set to detect a predetermined precursor ion in the first quadrupole, a fragmented in the collision quadrupole, and a predetermined fragment ion in the third quadrupole. It is a non-scanning technique, wherein each transition is detected individually and the detection of multiple transitions occurs concurrently in duty cycles.[6] This technique is being used to characterize the immune glycome.[6]

Glycobiology and medicine[10]

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[11] 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.

Vital to the proper functioning of skin, glycans undergo both qualitative and quantitative changes in the course of aging.[13] The functions of communication and metabolism are impaired and the skin’s architecture is degraded.

See also

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. 1 2 3 Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity". J Autoimmun 57 (6): 1–13. doi:10.1016/j.jaut.2014.12.002. PMID 25578468.
  7. ↑ Cold Spring Harbor Laboratory Press Essentials of Glycobiology, Second Edition
  8. ↑ Kreuger, J (2001). "Decoding heparan sulfate". Retrieved 2008-01-11.
  9. ↑ 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.
  10. ↑ "Pohlmann, La glycobiologie, une nouvelle arme pour la médecine ?". 2007. Arte. ZDF. Missing or empty |series= (help)
  11. ↑ Olden K, Bernard BA, Humphries M, et al. (1985). Function of glycoprotein glycans T.I.B.S. pp. 78–82.
  12. ↑ 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.
  13. ↑ 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.

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