Array ( [0] => {{Short description|Covalent attachment and further modification of carbohydrate residues to a substrate molecule}} [1] => {{dist|Glycation}} [2] => {{see also|Chemical glycosylation}} [3] => {{Use dmy dates|date=July 2020}} [4] => [5] => '''Glycosylation''' is the reaction in which a [[carbohydrate]] (or '[[glycan]]'), i.e. a [[glycosyl donor]], is attached to a hydroxyl or other functional group of another molecule (a [[glycosyl acceptor]]) in order to form a [[glycoconjugate]]. In biology (but not always in chemistry), '''glycosylation''' usually refers to an enzyme-catalysed reaction, whereas [[glycation]] (also 'non-enzymatic glycation' and 'non-enzymatic glycosylation') may refer to a non-enzymatic reaction.{{cite book |title=Encyclopedia of Biological Chemistry |section=Glycation |editor-last1=Lennarz |editor-first1=William J. |editor-last2=Lane |editor-first2=M. Daniel |last1=Lima |first1= M. |last2= Baynes |first2=J.W. |edition=Second |publisher=Academic Press |year=2013 |pages=405–411 |isbn=9780123786319 |doi=10.1016/B978-0-12-378630-2.00120-1}} [6] => [7] => Glycosylation is a form of co-translational and [[post-translational modification]]. Glycans serve a variety of structural and functional roles in membrane and secreted proteins.{{Cite book | edition = 2nd | publisher = Cold Spring Harbor Laboratories Press | isbn = 978-0-87969-770-9 | editor-first = Ajit | editor-last = Varki | name-list-style = vanc | title = Essentials of Glycobiology | url = https://www.ncbi.nlm.nih.gov/books/NBK1908/ | year = 2009 | pmid = 20301239 | last1 = Varki | first1 = A. | last2 = Cummings | first2 = R. D. | last3 = Esko | first3 = J. D. | last4 = Freeze | first4 = H. H. | last5 = Stanley | first5 = P. | last6 = Bertozzi | first6 = C. R. | last7 = Hart | first7 = G. W. | last8 = Etzler | first8 = M. E. }} The majority of proteins synthesized in the [[rough endoplasmic reticulum]] undergo glycosylation. Glycosylation is also present in the [[cytoplasm]] and nucleus as the [[O-GlcNAc|''O''-GlcNAc]] modification. Aglycosylation is a feature of engineered antibodies to bypass glycosylation.{{cite journal | vauthors = Jung ST, Kang TH, Kelton W, Georgiou G | title = Bypassing glycosylation: engineering aglycosylated full-length IgG antibodies for human therapy | journal = Current Opinion in Biotechnology | volume = 22 | issue = 6 | pages = 858–67 | date = December 2011 | pmid = 21420850 | doi = 10.1016/j.copbio.2011.03.002 }}{{cite journal|url=https://www.researchgate.net/publication/263802548|title=Transgenic plants of ''Nicotiana tabacum'' L. express aglycosylated monoclonal antibody with antitumor activity|year=2013|journal=Biotecnologia Aplicada}} Five classes of glycans are produced: [8] => * ''N''-linked glycans attached to a [[nitrogen]] of [[asparagine]] or [[arginine]] [[Side chain|side-chains]]. [[N-linked glycosylation|''N''-linked glycosylation]] requires participation of a special lipid called dolichol phosphate. [9] => * ''O''-linked glycans attached to the [[hydroxyl]] [[oxygen]] of [[serine]], [[threonine]], [[tyrosine]], [[hydroxylysine]], or [[hydroxyproline]] side-chains, or to oxygens on lipids such as [[ceramide]]. [10] => * Phosphoglycans linked through the phosphate of a phosphoserine. [11] => *''C''-linked glycans, a rare form of glycosylation where a sugar is added to a carbon on a [[tryptophan]] side-chain. [[Aloin]] is one of the few naturally occurring substances. [12] => * [[Glypiation]], which is the addition of a GPI anchor that links proteins to lipids through glycan linkages. [13] => [14] => == Purpose == [15] => Glycosylation is the process by which a [[carbohydrate]] is [[covalent]]ly attached to a target [[macromolecule]], typically [[protein]]s and [[lipid]]s. This modification serves various functions.{{Cite book | edition = 2nd | publisher = Oxford University Press, USA | isbn = 978-0-19-928278-4 | vauthors = Drickamer K, Taylor ME | title = Introduction to Glycobiology | year = 2006 }} For instance, some proteins do not fold correctly unless they are glycosylated. In other cases, proteins are not stable unless they contain [[oligosaccharide]]s linked at the [[amide]] [[nitrogen]] of certain [[asparagine]] residues. The influence of glycosylation on the folding and stability of [[glycoprotein]] is twofold. Firstly, the highly soluble glycans may have a direct physicochemical stabilisation effect. Secondly, ''N''-linked glycans mediate a critical quality control check point in glycoprotein folding in the endoplasmic reticulum.{{cite journal | vauthors = Dalziel M, Crispin M, Scanlan CN, Zitzmann N, Dwek RA | title = Emerging principles for the therapeutic exploitation of glycosylation | journal = Science | volume = 343 | issue = 6166 | pages = 1235681 | date = January 2014 | pmid = 24385630 | doi = 10.1126/science.1235681 | s2cid = 206548002 }} Glycosylation also plays a role in cell-to-cell adhesion (a mechanism employed by cells of the [[immune system]]) via [[Glycan-protein interactions|sugar-binding proteins]] called [[lectins]], which recognize specific carbohydrate moieties. Glycosylation is an important parameter in the optimization of many glycoprotein-based drugs such as [[monoclonal antibodies]]. Glycosylation also underpins the [[ABO blood group]] system. It is the presence or absence of [[glycosyltransferase]]s which dictates which blood group [[antigen]]s are presented and hence what antibody specificities are exhibited. This immunological role may well have driven the diversification of glycan heterogeneity and creates a barrier to [[zoonotic]] transmission of viruses.{{cite journal | vauthors = Crispin M, Harvey DJ, Bitto D, Bonomelli C, Edgeworth M, Scrivens JH, Huiskonen JT, Bowden TA | title = Structural plasticity of the Semliki Forest virus glycome upon interspecies transmission | language = EN | journal = Journal of Proteome Research | volume = 13 | issue = 3 | pages = 1702–12 | date = March 2014 | pmid = 24467287 | pmc = 4428802 | doi = 10.1021/pr401162k }} In addition, glycosylation is often used by viruses to shield the underlying viral protein from immune recognition. A significant example is the dense glycan shield of the envelope spike of the [[human immunodeficiency virus]].{{cite journal | vauthors = Crispin M, Doores KJ | title = Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design | journal = Current Opinion in Virology | volume = 11 | pages = 63–9 | date = April 2015 | pmid = 25747313 | pmc = 4827424 | doi = 10.1016/j.coviro.2015.02.002 | series = Viral pathogenesis • Preventive and therapeutic vaccines }} [16] => [17] => Overall, glycosylation needs to be understood by the likely evolutionary selection pressures that have shaped it. In one model, diversification can be considered purely as a result of endogenous functionality (such as [[cell trafficking]]). However, it is more likely that diversification is driven by evasion of pathogen infection mechanism (e.g. ''[[Helicobacter]]'' attachment to terminal saccharide residues) and that diversity within the multicellular organism is then exploited endogenously. [18] => [19] => Glycosylation can also module the thermodynamic and kinetic stability of the proteins.{{Cite journal|last1=Ardejani|first1=Maziar S.|last2=Noodleman|first2=Louis|last3=Powers|first3=Evan T.|last4=Kelly|first4=Jeffery W.|date=2021-03-15|title=Stereoelectronic effects in stabilizing protein– N -glycan interactions revealed by experiment and machine learning|journal=Nature Chemistry|volume=13|issue=5|language=en|pages=480–487|doi=10.1038/s41557-021-00646-w|pmid=33723379|pmc=8102341|bibcode=2021NatCh..13..480A|issn=1755-4349}} [20] => [21] => ==Glycoprotein diversity== [22] => [23] => Glycosylation increases diversity in the [[proteome]], because almost every aspect of glycosylation can be modified, including: [24] => *[[Glycosidic bond]]—the site of glycan linkage [25] => *[[Glycan composition]]—the types of sugars that are linked to a given protein [26] => *[[Glycan structure]]—can be unbranched or branched chains of sugars [27] => *[[Glycan length]]—can be short- or long-chain oligosaccharides [28] => [29] => == Mechanisms == [30] => [31] => There are various mechanisms for glycosylation, although most share several common features: [32] => *Glycosylation, unlike [[glycation]], is an enzymatic process. Indeed, glycosylation is thought to be the most complex [[Posttranslational modification|post-translational modification]], because of the large number of enzymatic steps involved.{{Cite book | publisher = Roberts and Co. Publishers, Englewood, CO | isbn = 978-0974707730 | last = Walsh | first = Christopher | name-list-style = vanc |title = Posttranslational Modification of Proteins: Expanding Nature's Inventory | year = 2006 }} [33] => *The donor molecule is often an activated [[nucleotide sugar]]. [34] => *The process is non-templated (unlike DNA [[Transcription (genetics)|transcription]] or protein [[Translation (biology)|translation]]); instead, the cell relies on segregating enzymes into different cellular compartments (e.g., [[endoplasmic reticulum]], cisternae in [[Golgi apparatus]]). Therefore, glycosylation is a site-specific modification. [35] => [36] => == Types == [37] => [38] => === ''N''-linked glycosylation === [39] => {{main|N-linked glycosylation}} [40] => ''N''-linked glycosylation is a very prevalent form of glycosylation and is important for the folding of many eukaryotic glycoproteins and for cell–cell and cell–[[extracellular matrix]] attachment. The ''N''-linked glycosylation process occurs in [[eukaryotes]] in the lumen of the endoplasmic reticulum and widely in [[archaea]], but very rarely in [[bacteria]]. In addition to their function in protein folding and cellular attachment, the ''N''-linked glycans of a protein can modulate a protein's function, in some cases acting as an on/off switch. [41] => [42] => === ''O''-linked glycosylation === [43] => {{main|O-linked glycosylation}} [44] => ''O''-linked glycosylation is a form of glycosylation that occurs in [[eukaryotes]] in the [[Golgi apparatus]],{{cite book|first=William G. |last=Flynne | name-list-style = vanc | title=Biotechnology and Bioengineering|url=https://books.google.com/books?id=WEBBP5IYqJQC&pg=PA45|year=2008|publisher=Nova Publishers|isbn=978-1-60456-067-1|pages=45ff}} but also occurs in [[archaea]] and [[bacteria]]. [45] => [46] => === Phosphoserine glycosylation === [47] => [[Xylose]], [[fucose]], [[mannose]], and [[GlcNAc]] [[phosphoserine]] [[glycan]]s have been reported in the literature. Fucose and GlcNAc have been found only in ''Dictyostelium discoideum'', mannose in ''[[Leishmania mexicana]]'', and xylose in ''[[Trypanosoma cruzi]]''. Mannose has recently been reported in a vertebrate, the mouse, ''Mus musculus'', on the cell-surface laminin receptor alpha dystroglycan4. It has been suggested this rare finding may be linked to the fact that alpha dystroglycan is highly conserved from lower vertebrates to mammals.{{cite journal | vauthors = Yoshida-Moriguchi T, Yu L, Stalnaker SH, Davis S, Kunz S, Madson M, Oldstone MB, Schachter H, Wells L, Campbell KP | title = ''O''-Mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding | journal = Science | volume = 327 | issue = 5961 | pages = 88–92 | date = January 2010 | pmid = 20044576 | pmc = 2978000 | doi = 10.1126/science.1180512 | bibcode = 2010Sci...327...88Y }} [48] => [49] => === ''C''-mannosylation === [50] => [[File:C-mannosylation process.svg|thumb|The mannose molecule is attached to the C2 of the first tryptophan of the sequence]] [51] => A [[mannose]] sugar is added to the first [[tryptophan]] residue in the sequence W–X–X–W (W indicates tryptophan; X is any amino acid). A [[C-C bond]] is formed between the first carbon of the [[Mannose|alpha-mannose]] and the second carbon of the tryptophan.{{Cite journal|last=Ihara|first=Yoshito|title=C-Mannosylation: A Modification on Tryptophan in Cellular Proteins|journal=Glycoscience: Biology and Medicine}} However, not all the sequences that have this pattern are mannosylated. It has been established that, in fact, only two thirds are and that there is a clear preference for the second [[amino acid]] to be one of the polar ones (Ser, [[Alanine|Ala]], [[Glycine|Gly]] and Thr) in order for mannosylation to occur. Recently there has been a breakthrough in the technique of predicting whether or not the sequence will have a mannosylation site that provides an accuracy of 93% opposed to the 67% accuracy if we just consider the WXXW motif. [52] => [53] => [[Thrombospondins]] are one of the proteins most commonly modified in this way. However, there is another group of proteins that undergo ''C''-mannosylation, type I [[cytokine receptor]]s.{{Cite journal |last=Aleksandra |first=Shcherbakova|title=C-mannosylation supports folding and enhances stability of thrombospondin repeats|journal=eLife|year=2019|volume=8|doi=10.7554/eLife.52978|pmid=31868591|pmc=6954052 |doi-access=free }} ''C''-mannosylation is unusual because the sugar is linked to a [[carbon]] rather than a reactive atom such as [[nitrogen]] or [[oxygen]]. In 2011, the first crystal structure of a protein containing this type of glycosylation was determined—that of human complement component 8.{{cite journal |doi=10.1074/jbc.M111.219766 |doi-access=free |title=Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement |pmid=21454577 |pmc=3093833 |year=2011 |journal=J Biol Chem |volume=286 |issue=20 |pages=17585–17592 |vauthors=Lovelace LL, Cooper CL, Sodetz JM, Lebioda L}} Currently it is established that 18% of human [[protein]]s, secreted and [[Transmembrane protein|transmembrane]] undergo the process of C-mannosylation.{{Cite journal|last=Julenius|first=Karin |date=May 2007 |title=NetCGlyc 1.0: prediction of mammalian C-mannosylation sites, K Julenius (2007)|journal=Glycobiology |volume=17|issue=8|pages=868–876|doi=10.1093/glycob/cwm050|pmid=17494086|doi-access=free |url=https://academic.oup.com/glycob/article/17/8/868/611571}} Numerous studies have shown that this process plays an important role in the secretion of [[Thrombospondin 1|Trombospondin type 1]] containing proteins which are retained in the [[endoplasmic reticulum]] if they do not undergo C-mannosylation This explains why a type of [[cytokine receptor]]s, [[erythropoietin receptor]] remained in the [[endoplasmic reticulum]] if it lacked C-mannosylation sites.{{Cite journal|last=Yoshimura |date=June 1992|title=Mutations in the Trp-Ser-X-Trp-Ser motif of the erythropoietin receptor abolish processing, ligand binding, and activation of the receptor |journal=The Journal of Biological Chemistry |volume=267|issue=16|pages=11619–25|doi=10.1016/S0021-9258(19)49956-0|pmid=1317872|doi-access=free}} [54] => [55] => === Formation of GPI anchors (glypiation) === [56] => [[Glypiation]] is a special form of glycosylation that features the formation of a [[GPI anchor]]. In this kind of glycosylation a protein is attached to a lipid anchor, via a glycan chain. (See also [[prenylation]].) [57] => [58] => === Chemical glycosylation === [59] => Glycosylation can also be effected using the tools of [[synthetic organic chemistry]]. Unlike the biochemical processes, synthetic glycochemistry relies heavily on protecting groups{{cite journal | vauthors = Crich D | title = Mechanism of a chemical glycosylation reaction | journal = Accounts of Chemical Research | volume = 43 | issue = 8 | pages = 1144–53 | date = August 2010 | pmid = 20496888 | doi = 10.1021/ar100035r }} (e.g. the 4,6-''O''-benzylidene) in order to achieve desired regioselectivity. The other challenge of chemical glycosylation is the stereoselectivity that each glycosidic linkage has two stereo-outcomes, α/β or ''cis''/''trans''. Generally, the α- or ''cis''-glycoside is more challenging to synthesis.{{cite journal | vauthors = Nigudkar SS, Demchenko AV | title = ''cis''-Glycosylation as the driving force of progress in synthetic carbohydrate chemistry | journal = Chemical Science | volume = 6 | issue = 5 | pages = 2687–2704 | date = May 2015 | pmid = 26078847 | pmc = 4465199 | doi = 10.1039/c5sc00280j }} New methods have been developed based on solvent participation or the formation of bicyclic sulfonium ions as chiral-auxiliary groups.{{cite journal | vauthors = Fang T, Gu Y, Huang W, Boons GJ | title = Mechanism of Glycosylation of Anomeric Sulfonium Ions | language = EN | journal = Journal of the American Chemical Society | volume = 138 | issue = 9 | pages = 3002–11 | date = March 2016 | pmid = 26878147 | pmc = 5078750 | doi = 10.1021/jacs.5b08436 }} [60] => [61] => === Non-enzymatic glycosylation === [62] => The non-enzymatic glycosylation is also known as [[glycation]] or non-enzymatic glycation. It is a spontaneous reaction and a type of [[post-translational modification]] of proteins meaning it alters their structure and biological activity. It is the [[Covalent bond|covalent]] attachment between the [[Carbonyl group|carbonil group]] of a reducing sugar (mainly glucose and fructose) and the amino acid [[side chain]] of the protein. In this process the intervention of an enzyme is not needed. It takes place across and close to the water channels and the protruding tubules.{{Cite journal|last1=Henle|first1=Thomas|last2=Duerasch|first2=Anja|last3=Weiz|first3=Alexander|last4=Ruck|first4=Michael|last5=Moeckel|first5=Ulrike|date=1 November 2020|title=Glycation Reactions of Casein Micelles|journal=Journal of Agricultural and Food Chemistry|volume=64|issue=14|pages=2953–2961|doi=10.1021/acs.jafc.6b00472|pmid=27018258}} [63] => [64] => At first, the reaction forms temporary molecules which later undergo different reactions ([[Amadori rearrangement]]s, [[Schiff base]] reactions, [[Maillard reaction]]s, [[Cross-link|crosslinkings]]...) and form permanent residues known as [[Advanced glycation end-product|Advanced Glycation end-products]] (AGEs). [65] => [66] => AGEs accumulate in long-lived extracellular proteins such as [[collagen]]{{Cite book|last1=Baynes|first1=J. W.|title=Encyclopedia of Biological Chemistry|last2=Lima|first2=M.|year=2013|isbn=978-0-12-378631-9|pages=405–411}} which is the most glycated and structurally abundant protein, especially in humans. Also, some studies have shown [[lysine]] may trigger spontaneous non-enzymatic glycosylation.{{cite journal | last1 = Świa̧tecka | first1 = D. | last2 = Kostyra | first2 = H. | last3 = Świa̧tecki | first3 = A. | year = 2010 | title = Impact of glycated pea proteins on the activity of free‐swimming and immobilised bacteria | url = | journal = J. Sci. Food Agric. | volume = 90 | issue = 11| pages = 1837–1845 | doi = 10.1002/jsfa.4022 | pmid = 20549652 }} [67] => [68] => ==== Role of AGEs ==== [69] => AGEs are responsible for many things. These molecules play an important role especially in nutrition, they are responsible for the brownish color and the aromas and flavors of some foods. It is demonstrated that cooking at high temperature results in various food products having high levels of AGEs.{{Cite journal |last1=Gill |first1=Vidhu |last2=Kumar |first2=Vijay |last3=Singh |first3=Kritanjali |last4=Kumar |first4=Ashok |last5=Kim |first5=Jong-Joo |date=2019-12-17 |title=Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health |journal=Biomolecules |language=en |volume=9 |issue=12 |pages=888 |doi=10.3390/biom9120888 |pmid=31861217 |pmc=6995512 |doi-access=free}} [70] => [71] => Having elevated levels of AGEs in the body has a direct impact on the development of many diseases. It has a direct implication in [[Type 2 diabetes|diabetes mellitus type 2]] that can lead to many complications such as: [[cataract]]s, [[Kidney failure|renal failure]], heart damage...{{Cite journal |last1=Ansari |first1=N.A. |last2=Rasheed |first2=Z. |date=March 2010 |title=НЕФЕРМЕНТАТИВНОЕ ГЛИКИРОВАНИЕ БЕЛКОВ: ОТ ДИАБЕТА ДО РАКА |trans-title=Non-enzymatic glycation of proteins: from diabetes to cancer |url=http://pbmc.ibmc.msk.ru/en/article-en/PBMC-2010-56-2-168 |journal=Biomeditsinskaya Khimiya |language=ru |volume=56 |issue=2 |pages=168–178 |doi=10.18097/pbmc20105602168 |pmid=21341505 |doi-access=free |issn=2310-6905}} And, if they are present at a decreased level, skin elasticity is reduced which is an important symptom of aging. [72] => [73] => They are also the precursors of many [[hormone]]s and regulate and modify their receptor mechanisms at the [[DNA]] level. [74] => [75] => ==Deglycosylation== [76] => There are different [[enzymes]] to remove the [[glycans]] from the [[proteins]] or remove some part of the [[sugar]] chain. [77] => * [[α2-3,6,8,9-Neuraminidase]] (from [[Arthrobacter ureafaciens]]): cleaves all non-reducing terminal branched and unbranched [[sialic acids]]. [78] => * [[β1,4-Galactosidase]] (from [[Streptococcus pneumoniae]]): releases only β1,4-linked, nonreducing terminal [[galactose]] from complex carbohydrates and [[glycoproteins]]. [79] => * [[β-N-Acetylglucosaminidase|β-''N''-Acetylglucosaminidase]] (from Streptococcus pneumoniae): cleaves all non-reducing terminal β-linked N-acetylglucosamine residues from complex carbohydrates and glycoproteins. [80] => * [[Endo-α-N-Acetylgalactosaminidase|''endo''-α-''N''-Acetylgalactosaminidase]] (''O''-glycosidase from ''[[Streptococcus pneumoniae]]''): removes ''O''-glycosylation. This enzyme cleaves [[serine]]- or [[threonine]]-linked unsubstituted Galβ1,3GalNAc [81] => * [[PNGase F]]: cleaves [[asparagine]]-linked oligosaccharides unless α1,3-core fucosylated. [82] => [83] => == Regulation of Notch signalling == [84] => [[Notch signaling|Notch signalling]] is a cell signalling pathway whose role is, among many others, to control the [[cell differentiation]] process in equivalent [[precursor cells]]. This means it is crucial in embryonic development, to the point that it has been tested on mice that the removal of glycans in Notch proteins can result in [[embryonic death]] or malformations of vital organs like the heart.{{cite journal |last1=Stanley |first1=Pamela |last2=Okajima |first2=Tetsuya |title=Roles of glycosylation in Notch signaling |journal=Current Topics in Developmental Biology |date=2010 |volume=92 |pages=131–164 |doi=10.1016/S0070-2153(10)92004-8 |pmid=20816394 |isbn=9780123809148 |url=https://pubmed.ncbi.nlm.nih.gov/20816394/ |access-date=2 November 2020}} [85] => [86] => Some of the specific modulators that control this process are [[glycosyltransferase]]s located in the [[endoplasmic reticulum]] and the [[Golgi apparatus]]. The Notch proteins go through these organelles in their maturation process and can be subject to different types of glycosylation: [[N-linked glycosylation]] and [[O-linked glycosylation]] (more specifically: O-linked glucose and O-linked fucose). [87] => [88] => All of the Notch proteins are modified by an O-fucose, because they share a common trait: O-fucosylation [[consensus sequence]]s.{{cite journal |last1=Haines |first1=Nicole |title=Glycosylation regulates Notch signalling |journal=Nature Reviews. Molecular Cell Biology |date=October 2003 |volume=4 |issue=10 |pages=786–797 |doi=10.1038/nrm1228 |pmid=14570055 |s2cid=22917106 |url=https://pubmed.ncbi.nlm.nih.gov/14570055/ |access-date=1 November 2020}} One of the modulators that intervene in this process is the Fringe, a glycosyltransferase that modifies the O-fucose to activate or deactivate parts of the signalling, acting as a positive or negative regulator, respectively. [89] => [90] => ==Clinical== [91] => [92] => There are three types of glycosylation disorders sorted by the type of alterations that are made to the glycosylation process: congenital alterations, acquired alterations and non-enzymatic acquired alterations. [93] => [94] => * '''Congenital alterations:''' Over 40 [[congenital disorder of glycosylation|congenital disorders of glycosylation]] (CGDs) have been reported in humans.{{cite book | vauthors = Jaeken J | title = Pediatric Neurology Part III | chapter = Congenital disorders of glycosylation | series = Handbook of Clinical Neurology | volume = 113 | pages = 1737–43 | year = 2013 | pmid = 23622397 | doi = 10.1016/B978-0-444-59565-2.00044-7 | isbn = 9780444595652 }} These can be divided into four groups: disorders of protein [[N-linked glycosylation|''N''-glycosylation]], disorders of protein ''O''-glycosylation, disorders of lipid glycosylation and disorders of other glycosylation pathways and of multiple glycosylation pathways. No effective treatment is known for any of these disorders. 80% of these affect the nervous system.{{citation needed|date=January 2018}} [95] => * '''Acquired alterations:''' In this second group the main disorders are infectious diseases, [[Autoimmune disease|autoimmune illnesses]] or [[cancer]]. In these cases, the changes in glycosylation are the cause of certain biological events. For example, in [[Rheumatoid arthritis|Rheumatoid Arthritis (RA)]], the body of the patient produces antibodies against the enzyme lymphocytes galactosyltransferase which inhibits the glycosylation of IgG. Therefore, the changes in the N-glycosylation produce the immunodeficiency involved in this illness. In this second group we can also find disorders caused by [[mutations]] on the enzymes that control the glycosylation of Notch proteins, such as [[Alagille syndrome]].{{cite journal |last1=Hideyuki |first1=Takeuchi |title=Significance of glycosylation in Notch signaling |journal=Biochemical and Biophysical Research Communications |date=17 October 2014 |volume=453 |issue=2 |pages=235–42 |doi=10.1016/j.bbrc.2014.05.115 |pmid=24909690 |pmc=4254162 |url=}} [96] => * '''Non-enzymatic acquired alterations:''' Non-enzymatic disorders, are also acquired, but they are due to the lack of enzymes that attach oligosaccharides to the protein. In this group the illnesses that stand out are [[Alzheimer's disease]] and [[diabetes]].{{cite journal |last1=Jiménez Martínez |first1=María del Carmen |title=Alteraciones de la glicosilación en enfermedades humanas |journal=Rev Inst Nal Enf Resp Mex |date=January–March 2002 |volume=15 |pages=39–47 |url=https://www.researchgate.net/publication/257938556 |access-date=2 November 2020}} [97] => [98] => All these diseases are difficult to diagnose because they do not only affect one organ, they affect many of them and in different ways. As a consequence, they are also hard to treat. However, thanks to the many advances that have been made in [[DNA sequencing|next-generation sequencing]], scientists can now understand better these disorders and have discovered new CDGs. [99] => {{cite journal |last1=S. Kane |first1=Megan |title=Mitotic Intragenic Recombination:A Mechanism of Survivalfor Several Congenital Disorders of Glycosylation |journal=The American Journal of Human Genetics |date=February 4, 2016 |volume=98 |issue=2 |pages=339–46 |doi=10.1016/j.ajhg.2015.12.007 |pmid=26805780 |pmc=4746335 |url=}} [100] => [101] => === Effects on therapeutic efficacy === [102] => It has been reported that mammalian glycosylation can improve the therapeutic efficacy of [[biotherapeutic]]s. For example, therapeutic efficacy of recombinant [[Interferon gamma|human interferon gamma]], expressed in [[HEK 293 cells|HEK 293]] platform, was improved against drug-resistant [[ovarian cancer]] cell lines.{{cite journal | vauthors = Razaghi A, Villacrés C, Jung V, Mashkour N, Butler M, Owens L, Heimann K | title = Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells | journal = Experimental Cell Research | volume = 359 | issue = 1 | pages = 20–29 | date = October 2017 | pmid = 28803068 | doi = 10.1016/j.yexcr.2017.08.014 | s2cid = 12800448 }} [103] => [104] => == See also == [105] => * {{annotated link|Advanced glycation endproduct}} [106] => * {{annotated link|Chemical glycosylation}} [107] => * {{annotated link|Fucosylation}} [108] => * {{annotated link|Glycation}} [109] => * {{annotated link|Glycorandomization}} [110] => [111] => == References == [112] => {{reflist}} [113] => [114] => == External links == [115] => * [http://crdd.osdd.net/raghava/glycoep/ GlycoEP] {{cite journal |vauthors=Chauhan JS, Rao A, Raghava GP |title=''In silico'' platform for prediction of N-, O- and C-glycosites in eukaryotic protein sequences |journal=PLOS ONE |volume=8 |issue=6 |pages=e67008 |date=2013 |doi=10.1371/journal.pone.0067008 |pmid=23840574 |pmc=3695939 |bibcode=2013PLoSO...867008C |doi-access=free }} [116] => * {{cite book |veditors=Varki A, Cummings R, Esko J, Freeze H, Hart G, Marth J |title=Essentials of Glycobiology |publisher=Cold Spring Harbor Laboratory Press |date=1999 |isbn=0-87969-559-5 |id=NBK20709 |url=https://www.ncbi.nlm.nih.gov/books/NBK20709/}} [117] => * [http://www.dkfz-heidelberg.de/spec/glyprot/ GlyProt: In-silico ''N''-glycosylation of proteins on the web]{{dead link|date=October 2017 |bot=InternetArchiveBot |fix-attempted=yes }} [118] => * [http://www.cbs.dtu.dk/services/NetNGlyc/ NetNGlyc: The NetNglyc server predicts ''N''-glycosylation sites in human proteins using artificial neural networks that examine the sequence context of Asn-Xaa-Ser/Thr sequons.] [119] => * [http://www.wiley-vch.de/home/thesugarcode Supplementary Material of the Book "The Sugar Code"] [120] => * [http://www.piercenet.com/browse.cfm?fldID=4E12331D-5056-8A76-4E72-1C5A427505F1 Additional information on glycosylation and figures] [121] => * {{cite journal | author=Emanual Maverakis |display-authors=etal | title=Glycans in the immune system and The Altered Glycan Theory of Autoimmunity | journal=Journal of Autoimmunity | volume=57 | pages=1–13 | doi=10.1016/j.jaut.2014.12.002 | pmid=25578468 | pmc=4340844 | year=2015 }} [122] => [123] => {{Metabolism}} [124] => [125] => [[Category:Post-translational modification]] [126] => [[Category:Organic reactions]] [127] => [[Category:Carbohydrates]] [128] => [[Category:Carbohydrate chemistry]] [129] => [[Category:Biochemistry]] [130] => [[Category:Congenital disorders of glycosylation]] [] => )
good wiki

Glycosylation

Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i. e.

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