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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.
- 5Modern tools and techniques for glycan structure prediction and study of glycan-binding ligands
History[edit]
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[edit]
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-linked glycans of a protein can modulate the protein's function, in some cases acting as an on-off switch.[6]
Glycomics[edit]
'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][8]
Challenges in the study of sugar structures[edit]
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.[9] 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.[10]
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 and study of glycan-binding ligands[edit]
Advanced 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.[11]
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 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]
Medicine[edit]
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.[12] 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[edit]
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.[13]
- 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.[14] The functions of communication and metabolism are impaired and the skin's architecture is degraded.
See also[edit]
References[edit]
- ^Varki A, Cummings R, Esko J, Freeze H, Stanley P, Bertozzi C, Hart G, Etzler M (2008). Essentials of glycobiology. Cold Spring Harbor Laboratory Press; 2nd edition. ISBN978-0-87969-770-9.
- ^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.
- ^Rademacher TW, Parekh RB, Dwek RA (1988). 'Glycobiology'. Annu. Rev. Biochem. 57 (1): 785–838. doi:10.1146/annurev.bi.57.070188.004033. PMID3052290.
- ^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. PMID15047148.
- ^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. PMID15090734.
- ^ 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. PMID25578468.
- ^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. PMID27004978.
- ^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. PMC2892900. PMID18758488.
- ^Aizpurua-Olaizola, O.; Sastre Toraño, 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. ISSN0165-9936.
- ^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. PMID18708125.
- ^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. ISSN1600-0625.
External links[edit]
- The Functional Glycomics Gateway. monthly updated web resource, a collaboration of Nature and the Consortium for Functional Glycomics.
- Emanual Maverakis; et al. 'Glycans in the immune system and The Altered Glycan Theory of Autoimmunity'(PDF).
Have you ever heard of pneumonoultramicroscopicsilicovolcanoconiosis? This is an actual word, but don't let that scare you. Some science terms can be difficult to comprehend: By identifying the affixes -- elements added before and after base words -- you can understand even the most complex terms. This index will help you identify some commonly used prefixes and suffixes in biology.
Common Prefixes
(Ana-): indicates upward direction, synthesis or buildup, repetition, excess or separation.
(Angio-): signifies a type of receptacles such as a vessel or shell.
(Arthr- or Arthro-): refers to a joint or a junction that separates different parts.
(Auto-): identifies something as belonging to oneself, occurring within or occurring spontaneously.
(Blast- , -blast): indicates an immature developmental stage.
(Cephal- or Cephalo-): referring to the head.
(Chrom- or Chromo-): denotes color or pigmentation.
(Cyto- or Cyte-): regarding or relating to a cell.
(Dactyl-, -dactyl): refers to a digit or tactile appendages such as a finger or toe.
(Diplo-): means double, paired or twofold.
(Ect- or Ecto-): means outer or external.
(End- or Endo-): means inner or internal.
- 5Modern tools and techniques for glycan structure prediction and study of glycan-binding ligands
History[edit]
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[edit]
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-linked glycans of a protein can modulate the protein's function, in some cases acting as an on-off switch.[6]
Glycomics[edit]
'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][8]
Challenges in the study of sugar structures[edit]
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.[9] 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.[10]
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 and study of glycan-binding ligands[edit]
Advanced 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.[11]
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 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]
Medicine[edit]
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.[12] 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[edit]
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.[13]
- 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.[14] The functions of communication and metabolism are impaired and the skin's architecture is degraded.
See also[edit]
References[edit]
- ^Varki A, Cummings R, Esko J, Freeze H, Stanley P, Bertozzi C, Hart G, Etzler M (2008). Essentials of glycobiology. Cold Spring Harbor Laboratory Press; 2nd edition. ISBN978-0-87969-770-9.
- ^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.
- ^Rademacher TW, Parekh RB, Dwek RA (1988). 'Glycobiology'. Annu. Rev. Biochem. 57 (1): 785–838. doi:10.1146/annurev.bi.57.070188.004033. PMID3052290.
- ^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. PMID15047148.
- ^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. PMID15090734.
- ^ 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. PMID25578468.
- ^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. PMID27004978.
- ^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. PMC2892900. PMID18758488.
- ^Aizpurua-Olaizola, O.; Sastre Toraño, 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. ISSN0165-9936.
- ^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. PMID18708125.
- ^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. ISSN1600-0625.
External links[edit]
- The Functional Glycomics Gateway. monthly updated web resource, a collaboration of Nature and the Consortium for Functional Glycomics.
- Emanual Maverakis; et al. 'Glycans in the immune system and The Altered Glycan Theory of Autoimmunity'(PDF).
Have you ever heard of pneumonoultramicroscopicsilicovolcanoconiosis? This is an actual word, but don't let that scare you. Some science terms can be difficult to comprehend: By identifying the affixes -- elements added before and after base words -- you can understand even the most complex terms. This index will help you identify some commonly used prefixes and suffixes in biology.
Common Prefixes
(Ana-): indicates upward direction, synthesis or buildup, repetition, excess or separation.
(Angio-): signifies a type of receptacles such as a vessel or shell.
(Arthr- or Arthro-): refers to a joint or a junction that separates different parts.
(Auto-): identifies something as belonging to oneself, occurring within or occurring spontaneously.
(Blast- , -blast): indicates an immature developmental stage.
(Cephal- or Cephalo-): referring to the head.
(Chrom- or Chromo-): denotes color or pigmentation.
(Cyto- or Cyte-): regarding or relating to a cell.
(Dactyl-, -dactyl): refers to a digit or tactile appendages such as a finger or toe.
(Diplo-): means double, paired or twofold.
(Ect- or Ecto-): means outer or external.
(End- or Endo-): means inner or internal.
(Epi-): indicates a position that is above, on or near a surface.
(Erythr- or Erythro-): means red or reddish in color.
(Ex- or Exo-): means external, out of or away from.
(Eu-): means genuine, true, well or good.
(Gam-, Gamo or -gamy): refers to fertilization, sexual reproduction or marriage.
(Glyco- or Gluco-): pertains to a sugar or a sugar derivative.
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(Haplo-): means single or simple.
(Hem-, Hemo- or Hemato-): denoting blood or blood components (plasma and blood cells).
(Heter- or Hetero-): means unlike, different or other.
(Karyo- or Caryo-): means nut or kernel, and also refers to the nucleus of a cell.
(Meso-): means middle or intermediate.
(My- or Myo-): means muscle.
(Neur- or Neuro-): referring to nerves or the nervous system.
(Peri-): means surrounding, near or around.
(Phag- or Phago-): pertaining to eating, swallowing or consuming.
(Poly-): means many or excessive.
(Proto-): means primary or primitive.
(Staphyl- or Staphylo-): referring to a cluster or bunch.
(Tel- or Telo-): denoting an end, extremity or final phase.
(Zo- or Zoo-): pertaining an animal or animal life.
Common Suffixes
(-ase): denoting an enzyme. In enzyme naming, this suffix is added to the end of the substrate name.
(-derm or -dermis): referring to tissue or skin.
(-ectomy or -stomy): pertaining to the act of cutting out or the surgical removal of tissue.
(-emia or -aemia): referring to a condition of the blood or the presence of a substance in the blood.
(-genic): means giving rise to, producing or forming.
(-itis): denoting inflammation, commonly of a tissue or organ.
(-kinesis or -kinesia): indicating activity or movement.
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(-lysis): referring to degradation, decomposition, bursting or releasing.
(-oma): indicating an abnormal growth or tumor.
(-osis or -otic): indicating a disease or abnormal production of a substance.
(-otomy or -tomy): denoting an incision or surgical cut.
(-penia): pertaining to a deficiency or lack.
(-phage or -phagia): the act of eating or consuming.
(-phile or -philic): having an affinity for or strong attraction to something specific.
(-plasm or -plasmo): referring to tissue or a living substance.
(-scope): denoting an instrument used for observation or examination.
(-stasis): indicating the maintenance of a constant state.
(-troph or -trophy): pertaining to nourishment or a method of nutrient acquisition.
Other Tips
While knowing suffixes and prefixes will tell you much about biological terms, it's helpful to know a few other tricks for deciphering their meanings, including:
- Breaking down words: Breaking down biological terms into their component parts can help you decipher their meanings.
- Dissections: Just as you might dissect a frog 'to separate (it) into pieces,' as Merriam-Webster explains, you can also break down a biological term to 'expose' its 'several parts for scientific examination.'
