Editing Glycation

{{Short description|Attachment of a sugar to a protein or lipid}}
{{dist|Glycosylation}}

'''Glycation''' ('''non-enzymatic glycosylation''') is the [[covalent bond|covalent]] attachment of a sugar to a [[protein]],  [[lipid]] or [[nucleic acid]] molecule.<ref name=":0">{{Citation|last1=Lima|first1=M.|title=Glycation|date=2013-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780123786302001201|encyclopedia=Encyclopedia of Biological Chemistry (Second Edition)|pages=405–411|editor-last=Lennarz|editor-first=William J.|place=Waltham|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-378630-2.00120-1|isbn=978-0-12-378631-9|access-date=2020-12-16|last2=Baynes|first2=J. W.|editor2-last=Lane|editor2-first=M. Daniel|url-access=subscription}}</ref> Typical sugars that participate in glycation are [[glucose]], [[fructose]], and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in [[diabetes mellitus]] and is implicated in some diseases and in aging.<ref>{{Cite journal| last1 = Glenn | first1 = J.| last2 = Stitt | first2 = A.| title = The role of advanced glycation end products in retinal ageing and disease| journal = Biochimica et Biophysica Acta (BBA) - General Subjects| volume = 1790| issue = 10| pages = 1109–1116| year = 2009| pmid = 19409449| doi = 10.1016/j.bbagen.2009.04.016}}</ref><ref>{{Cite journal| doi = 10.1007/BF03325227| pmid = 19448391| year = 2009| last1 = Semba | first1 = R. D.| last2 = Ferrucci| last3 = Sun| last4 = Beck| last5 = Dalal| last6 = Varadhan| last7 = Walston| last8 = Guralnik| last9 = Fried| title = Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women| volume = 21| issue = 2| pages = 182–190| journal = Aging Clinical and Experimental Research | first2 = L. | first3 = K. | first4 = J. | first5 = M. | first6 = R. | first7 = J. | first8 = J. M. | first9 = L. P.| pmc = 2684987}}</ref><ref>{{Cite journal| last1 = Semba | first1 = R.| last2 = Najjar | first2 = S.| last3 = Sun | first3 = K.| last4 = Lakatta | first4 = E.| last5 = Ferrucci | first5 = L.| title = Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults| journal = American Journal of Hypertension| volume = 22| issue = 1| pages = 74–79| year = 2009| pmid = 19023277| doi = 10.1038/ajh.2008.320| pmc = 2637811}}</ref> Glycation end products are believed to play a causative role in the vascular complications of [[diabetes mellitus]].<ref>{{Cite journal| pmid = 18331228| year = 2007| last1 = Yan | first1 = S. F.| last2 = D'Agati| last3 = Schmidt| last4 = Ramasamy| title = Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging| volume = 7| issue = 8| pages = 699–710| journal = Current Molecular Medicine| doi = 10.2174/156652407783220732 | first2 = V. | first3 = A. M. | first4 = R.}}</ref>

In contrast with glycation, [[glycosylation]] is the enzyme-mediated ATP-dependent attachment of sugars to a protein or lipid.<ref name=":0" /> Glycosylation occurs at defined sites on the target molecule. It is a common form of [[post-translational modification]] of proteins and is required for the functioning of the mature protein.

==Biochemistry==
[[File:GlycationViaAmadoriRgmt.svg|thumb|364px|Glycation pathway via [[Amadori rearrangement]] (in HbA1c, R is typically N-terminal valine)<ref>{{cite journal|title=Chemistry of Amadori Rearrangement Products: Analysis, Synthesis, Kinetics, Reactions, and Spectroscopic Properties|author1= Yaylayan, Varoujan A. |author2=Huyghues-Despointes, Alexis |journal=Critical Reviews in Food Science and Nutrition|year=1994|volume=34|issue= 4|pages=321–69|doi=10.1080/10408399409527667|pmid= 7945894}}</ref>]]
[[File:HydroimidazoloneAGE.png|thumb|right|266px|[[Imidazolone]]s (R = CH<sub>2</sub>CH(OH)CH(OH)CH<sub>2</sub>OH) are typical glycation products. They arise by the condensation of 3-deoxyglucosone with the guanidine group of an [[arginine]] residue.<ref name=DRCP>{{cite journal|journal=Diabetes Research and Clinical Practice|volume=148|year=2019|title=Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer|first1=Justine|last1=Bellier|first2=Marie-Julie|last2=Nokin|first3=Eva|last3= Lardé|first4=Philippe|last4=Karoyan|first5=Olivier|last5=Peulen|first6=Vincent|last6=Castronovo|first7=Akeila|last7=Bellahcène|pages=200–211|doi=10.1016/j.diabres.2019.01.002|pmid=30664892|s2cid=58631777 }}</ref>]]
Glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: [[glucose]], [[fructose]], and [[galactose]]. It appears that fructose has approximately ten times the glycation activity of glucose, the primary body fuel.<ref>{{cite journal |doi=10.1021/bi00406a016 |vauthors=McPherson JD, Shilton BH, Walton DJ |title=Role of fructose in glycation and cross-linking of proteins |journal=Biochemistry |volume=27 |issue=6 |pages=1901–7 |date=March 1988 |pmid=3132203}}</ref>  Glycation can occur through [[Amadori product|Amadori reaction]]s, [[Schiff base|Schiff base reaction]]s, and [[Maillard reaction]]s; which lead to [[advanced glycation end product]]s (AGEs).<ref name=":0" />

==Biomedical implications==
Red blood cells have a consistent lifespan of 120 days and are accessible for measurement of [[glycated hemoglobin]]. Measurement of [[HbA1c]]—the predominant form of glycated hemoglobin—enables medium-term blood sugar control to be monitored in [[diabetes]].

Some glycation products are implicated in many age-related chronic diseases, including [[cardiovascular disease]]s (the endothelium, fibrinogen, and collagen are damaged) and [[Alzheimer's disease]] (amyloid proteins are side-products of the reactions progressing to AGEs).<ref>{{cite journal|last=Münch|first=Gerald|title=Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of β-amyloid peptide|journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease|date=27 February 1997|volume=1360|issue=1|pages=17–29|doi=10.1016/S0925-4439(96)00062-2|pmid=9061036|display-authors=etal|doi-access=}}</ref><ref>{{cite journal|last=Munch|first=G|author2=Deuther-Conrad W |author3=Gasic-Milenkovic J. |title=Glycoxidative stress creates a vicious cycle of neurodegeneration in Alzheimer's disease--a target for neuroprotective treatment strategies?|journal=J Neural Transm Suppl|year=2002|volume=62|pages=303–307|pmid= 12456073|issue=62|doi=10.1007/978-3-7091-6139-5_28}}</ref>

Long-lived cells (such as nerves and different types of brain cell), long-lasting proteins (such as [[crystallin]]s of the [[lens (anatomy)|lens]] and [[cornea]]), and DNA can sustain substantial glycation over time.  Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure, especially in diabetes.<ref>{{cite journal|last=Soldatos|first=G.|author2=Cooper ME|title=Advanced glycation end products and vascular structure and function|journal=Curr Hypertens Rep|date=Dec 2006|volume=8|issue=6|pages=472–478|pmid=17087858|doi=10.1007/s11906-006-0025-8|s2cid=31239347}}</ref> Glycations also cause weakening of the collagen in the blood vessel walls,<ref>{{cite journal|last=Lee|first=J. Michael|author2=Samuel P. Veres|title=Advanced glycation end-product cross-linking inhibits biomechanical plasticity and characteristic failure morphology of native tendon|journal=Journal of Applied Physiology|date=2019-04-02|volume=126|issue=4|pages=832–841|doi=10.1152/japplphysiol.00430.2018|pmid=30653412|pmc=6485690}}</ref> which may lead to micro- or macro-aneurysm; this may cause strokes if in the brain.

==DNA glycation==
The term DNA glycation applies to [[DNA damage (naturally occurring)|DNA damage]] induced by reactive carbonyls (principally [[methylglyoxal]] and [[glyoxal]]) that are present in cells as by-products of sugar metabolism.<ref name = Richarme2017>Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science. 2017 Jul 14;357(6347):208-211. doi: 10.1126/science.aag1095. Epub 2017 Jun 8. PMID 28596309</ref>  Glycation of DNA can cause [[mutation]], breaks in DNA and [[cytotoxicity]].<ref name = Richarme2017/>  [[Guanine]] in DNA is the base most susceptible to glycation.  Glycated DNA, as a form of damage, appears to be as frequent as the more well studied oxidative DNA damage.  A protein, designated DJ-1 (also known as [[PARK7]]), is employed in the repair of glycated DNA bases in humans, and homologs of this protein have also been identified in bacteria.<ref name = Richarme2017/>

==See also==
* [[Advanced glycation end-product]]
* [[Alagebrium]]
* [[Fructose]]
* [[Galactose]]
* [[Glucose]]
* [[Glycosylation]]
* [[Glycated hemoglobin]]
* [[List of aging processes]]

==Additional reading==
* {{cite journal |vauthors=Ahmed N, Furth AJ |title=Failure of common glycation assays to detect glycation by fructose |journal=Clin. Chem. |volume=38 |issue=7 |pages=1301–3 |date=July 1992 |doi=10.1093/clinchem/38.7.1301 |pmid=1623595|doi-access=free }}
* {{cite journal |author=Vlassara H |title=Advanced glycation in health and disease: role of the modern environment |journal=Annals of the New York Academy of Sciences |volume=1043 |issue= 1|pages=452–60 |date=June 2005 |pmid=16037266 |doi=10.1196/annals.1333.051|bibcode = 2005NYASA1043..452V |s2cid=20952378 }}

==References==
{{reflist|2}}

[[Category:Ageing processes]]
[[Category:Carbohydrates]]
[[Category:Post-translational modification]]
[[Category:Protein metabolism]]