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.
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. Each year the Society of Glycobiology awards the Rosalind Kornfeld award for lifetime achievement in the field of glycobiology.[4]
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 membrane 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.[5][6] In addition to their function in protein folding and cellular attachment, the N-linked glycans of a protein can modulate the protein's function, in some cases acting as an on-off switch.[7]
"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.[8][9]
Challenges in the study of sugar structuresEdit
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.[10] 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.[11]
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 predictionEdit
One of the most widely used techniques is mass spectrometry which uses three principal units: the ionizer, analyzer and detector.
Glycan arrays, like that offered by the Consortium for Functional Glycomics and Z Biotech LLC, contain carbohydrate compounds that can be screened with lectins or antibodies to define carbohydrate specificity and identify ligands.
Multiple reaction monitoring (MRM)Edit
MRM is a mass spectrometry-based technique that has recently been used for site-specific glycosylation 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.[7] This technique is being used to characterize the immune glycome.[7]
MedicineEdit
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.[13] 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.
SkinEdit
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.[14]
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.[15] The functions of communication and metabolism are impaired and the skin's architecture is degraded.
^Varki A, Cummings RD, Esko JD, Stanley P, Hart GW, Aebi M, Mohnen D, Kinoshita T, Packer NH, Prestegard JH, Schnaar RL, Seeberger PH (2022). Essentials of Glycobiology (4th ed.). Cold Spring Harbor Laboratory Press. doi:10.1101/9781621824213 (inactive 1 August 2023). ISBN978-1-621824-21-3. PMID 35536922.{{cite book}}: CS1 maint: DOI inactive as of August 2023 (link)
^Varki A, Cummings R, Esko J, Freeze H, Hart G, Marth J (1999). Essentials of glycobiology. Cold Spring Harbor Laboratory Press. ISBN0-87969-560-9.
^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. S2CID 1110879.
^ abcMaverakis 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. PMC4340844. PMID 25578468.
^Cold Spring Harbor Laboratory Press Essentials of Glycobiology, Second Edition
^Schnaar, RL (June 2016). "Glycobiology simplified: diverse roles of glycan recognition in inflammation". Journal of Leukocyte Biology. 99 (6): 825–38. doi:10.1189/jlb.3RI0116-021R. PMC4952015. PMID 27004978.
^Marth, JD (2008). "A unified vision of the building blocks of life". Nature Cell Biology. 10 (9): 1015–6. doi:10.1038/ncb0908-1015. PMC2892900. PMID 18758488.
^Olden K, Bernard BA, Humphries M, et al. (1985). Function of glycoprotein glycans T.I.B.S. pp. 78–82.
^Faury, G (December 2008). "The alpha-L-Rhamnose recognizing lectin site of human dermal fibroblasts functions as a signal transducer: modulation of Ca2+ fluxes and gene expression". Biochimica et Biophysica Acta. 1780 (12): 1388–94. doi:10.1016/j.bbagen.2008.07.008. PMID 18708125.
^Oh, Jang-Hee; Kim, Yeon Kyung; Jung, Ji-Yong; Shin, Jeong-eun; Chung, Jin Ho (2011). "Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo". Experimental Dermatology. 20 (5): 454–456. doi:10.1111/j.1600-0625.2011.01258.x. ISSN 1600-0625. PMID 21426414. S2CID 34434784.
glycobiology, journal, journal, defined, narrowest, sense, glycobiology, study, structure, biosynthesis, biology, saccharides, sugar, chains, glycans, that, widely, distributed, nature, sugars, saccharides, essential, components, living, things, aspects, vario. 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 Contents 1 History 2 Glycoconjugates 3 Glycomics 4 Challenges in the study of sugar structures 5 Modern tools and techniques for glycan structure prediction 5 1 Multiple reaction monitoring MRM 6 Medicine 7 Skin 8 See also 9 References 10 External linksHistory EditAccording 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 Each year the Society of Glycobiology awards the Rosalind Kornfeld award for lifetime achievement in the field of glycobiology 4 Glycoconjugates EditMain 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 membrane 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 5 6 In addition to their function in protein folding and cellular attachment the N linked glycans of a protein can modulate the protein s function in some cases acting as an on off switch 7 Glycomics EditMain 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 8 9 Challenges in the study of sugar structures EditPart 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 10 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 11 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 EditAdvanced analytical instruments and software programs when used in combination can unlock the mystery of glycan structures Current techniques for structural annotation and analysis of glycans include liquid chromatography LC capillary electrophoresis CE mass spectrometry MS nuclear magnetic resonance NMR and lectin arrays 12 One of the most widely used techniques is mass spectrometry which uses three principal units the ionizer analyzer and detector Glycan arrays like that offered by the Consortium for Functional Glycomics and Z Biotech LLC contain carbohydrate compounds that can be screened with lectins or antibodies to define carbohydrate specificity and identify ligands Multiple reaction monitoring MRM Edit MRM is a mass spectrometry based technique that has recently been used for site specific glycosylation 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 7 This technique is being used to characterize the immune glycome 7 Medicine EditDrugs 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 13 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 Skin EditGlycobiology 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 14 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 15 The functions of communication and metabolism are impaired and the skin s architecture is degraded See also EditSugar signal transduction Glycan protein interactionsReferences Edit Varki A Cummings RD Esko JD Stanley P Hart GW Aebi M Mohnen D Kinoshita T Packer NH Prestegard JH Schnaar RL Seeberger PH 2022 Essentials of Glycobiology 4th ed Cold Spring Harbor Laboratory Press doi 10 1101 9781621824213 inactive 1 August 2023 ISBN 978 1 621824 21 3 PMID 35536922 a href Template Cite book html title Template Cite book cite book a CS1 maint DOI inactive as of August 2023 link Varki A Cummings R Esko J Freeze H Hart G Marth J 1999 Essentials of glycobiology Cold Spring Harbor Laboratory Press ISBN 0 87969 560 9 Rademacher TW Parekh RB Dwek RA 1988 Glycobiology Annu Rev Biochem 57 1 785 838 doi 10 1146 annurev bi 57 070188 004033 PMID 3052290 Rosalind Kornfeld Award www glycobiology org Retrieved 2021 11 05 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 S2CID 1110879 a b c 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 PMC 4340844 PMID 25578468 Cold Spring Harbor Laboratory Press Essentials of Glycobiology Second Edition Schnaar RL June 2016 Glycobiology simplified diverse roles of glycan recognition in inflammation Journal of Leukocyte Biology 99 6 825 38 doi 10 1189 jlb 3RI0116 021R PMC 4952015 PMID 27004978 Kreuger J 2001 Decoding heparan sulfate Retrieved 2008 01 11 a href Template Cite journal html title Template Cite journal cite journal a Cite journal requires journal help 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 Aizpurua Olaizola O Sastre Torano J Falcon Perez J M Williams C Reichardt N Boons G J March 2018 Mass spectrometry for glycan biomarker discovery TrAC Trends in Analytical Chemistry 100 7 14 doi 10 1016 j trac 2017 12 015 ISSN 0165 9936 Olden K Bernard BA Humphries M et al 1985 Function of glycoprotein glycans T I B S pp 78 82 Faury G December 2008 The alpha L Rhamnose recognizing lectin site of human dermal fibroblasts functions as a signal transducer modulation of Ca2 fluxes and gene expression Biochimica et Biophysica Acta 1780 12 1388 94 doi 10 1016 j bbagen 2008 07 008 PMID 18708125 Oh Jang Hee Kim Yeon Kyung Jung Ji Yong Shin Jeong eun Chung Jin Ho 2011 Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo Experimental Dermatology 20 5 454 456 doi 10 1111 j 1600 0625 2011 01258 x ISSN 1600 0625 PMID 21426414 S2CID 34434784 External links EditVendor 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 Emanual Maverakis et al Glycans in the immune system and The Altered Glycan Theory of Autoimmunity PDF http www healthcanal com medical breakthroughs 22037 UGA scientists team define first ever sequence biologically important carbohydrate html Retrieved from https en wikipedia org w index php title Glycobiology amp oldid 1168149622, wikipedia, wiki, book, books, library,
