| Revision as of 17:49, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Saving copy of the {{chembox}} taken from revid 456620058 of page 3-Deoxyglucosone for the Chem/Drugbox validation project (updated: 'CASNo'). |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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| ImageFile = 3-Deoxyglucosone.svg |
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| ImageFile = 3-Deoxyglucosone.svg |
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| IUPACName = (4''S'',5''R'')-4,5,6-Trihydroxy-2-oxohexanal |
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| IUPACName = 3-Deoxy-<small>D</small>-''erythro''-hexos-2-ulose |
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| SystematicName = (4''S'',5''R'')-4,5,6-Trihydroxy-2-oxohexanal |
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| OtherNames = 3-Deoxy-<small>D</small>-erythro-hexosulose; 2-Keto-3-deoxyglucose; 3-Deoxy-<small>D</small>-erythro-hexos-2-ulose; 3-Deoxy-<small>D</small>-erythro-hexosulose; 3-Deoxy-<small>D</small>-glucosone; <small>D</small>-3-Deoxyglucosone |
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| OtherNames = 3-Deoxy-<small>D</small>-''erythro''-hexosulose; 2-Keto-3-deoxyglucose; 3-Deoxy-<small>D</small>-''erythro''-hexosulose; 3-Deoxy-<small>D</small>-glucosone; <small>D</small>-3-Deoxyglucosone |
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| Section1 = {{Chembox Identifiers |
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| StdInChIKey = ZGCHLOWZNKRZSN-NTSWFWBYSA-N |
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| StdInChIKey = ZGCHLOWZNKRZSN-NTSWFWBYSA-N |
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| CASNo = <!-- blanked - oldvalue: 4084-27-9 --> |
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| CASNo = 4084-27-9 |
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| UNII = EXV5374VEY |
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| PubChem = 114839 |
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| C=6|H=10|O=5 |
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| Density = 1.406 g/ml |
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'''3-Deoxyglucosone''' ('''3DG''') is a sugar that is notable because it is a marker for diabetes. 3DG reacts with protein to form ]s (AGEs), which contribute to diseases such as the vascular complications of ], ], ], ], ], and ].<ref name=Niwa/> |
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==Biosynthesis== |
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] arise from the condensation of arginine residues and 3-deoxyglucosone (R = CH<sub>2</sub>CH(OH)CH(OH)CH<sub>2</sub>OH).<ref name=DRCP>{{cite journal|journal=Diabetes Research and Clinical Practice|volume=148|pages=200–211|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|doi=10.1016/j.diabres.2019.01.002|pmid=30664892|s2cid=58631777 }}</ref>]] 3DG is made naturally via the ]. It forms after glucose reacts with primary amino groups of lysine or arginine found in proteins. Because of the increased concentration of the reactant glucose, more 3DG forms with excessive blood sugar levels, as in uncontrolled ]. Glucose reacts non-enzymatically with protein amino groups to initiate ]. The formation of 3DG may account for the numerous complications of diabetes as well as aging.<ref name=Niwa/> |
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3DG arises also via the degradation of ] (F3P).<ref>{{cite journal | vauthors = Szwergold BS, Kappler F, Brown TR | title = Identification of fructose 3-phosphate in the lens of diabetic rats | journal = Science | volume = 247 | issue = 4941 | pages = 451–4 | date = January 1990 | pmid = 2300805 | doi = 10.1126/science.2300805 | bibcode = 1990Sci...247..451S }}</ref> 3DG plays a central role in the development of diabetic complications via the action of fructosamine-3-kinase.{{Cn|date=February 2021}} |
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==Biochemistry== |
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As a dicarbonyl sugar, i.e. one with the grouping R-C(O)-C(O)-R, 3DG is highly reactive toward amine groups. Amines are common in amino acids as well as some nucleic acids. The products from the reaction of 3DG with protein amino groups are called ]s (AGEs). AGEs include ]s, ], N<sup>6</sup>-(carboxymethyl)lysine, and ]. 3DG as well as AGEs play a role in the modification and cross-linking of long-lived proteins such as ] and ], contributing to diseases such as the vascular complications of ], ], ], ], ], and ].<ref name=Niwa/> |
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3DG has a variety of potential biological effects, particularly when it is present at elevated concentrations in diabetic states: |
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* Diabetics with ] were found to have elevated plasma levels of 3DG compared with other diabetics.<ref>{{cite journal | vauthors = Kusunoki H, Miyata S, Ohara T, Liu BF, Uriuhara A, Kojima H, Suzuki K, Miyazaki H, Yamashita Y, Inaba K, Kasuga M | title = Relation between serum 3-deoxyglucosone and development of diabetic microangiopathy | journal = Diabetes Care | volume = 26 | issue = 6 | pages = 1889–94 | date = June 2003 | pmid = 12766129 | doi = 10.2337/diacare.26.6.1889 | doi-access = free | hdl = 20.500.14094/D2002787 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Wells-Knecht KJ, Lyons TJ, McCance DR, Thorpe SR, Feather MS, Baynes JW | title = 3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes | journal = Diabetes | volume = 43 | issue = 9 | pages = 1152–6 | date = September 1994 | pmid = 8070616 | doi = 10.2337/diabetes.43.9.1152 }}</ref><ref name=Niwa>{{cite journal|doi=10.1016/S0378-4347(99)00113-9|pmid=10491986|title=3-Deoxyglucosone: Metabolism, analysis, biological activity, and clinical implication|journal=Journal of Chromatography B: Biomedical Sciences and Applications|volume=731|issue=1|pages=23–36|year=1999|last1=Niwa|first1=Toshimitsu}}</ref> |
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* Glycated diet, which elevates systemic 3DG levels, leads to diabetes-like tubular and glomerular kidney pathology.<ref>{{cite journal | vauthors = Kappler F, Schwartz ML, Su B, Tobia AM, Brown T | title = DYN 12, a small molecule inhibitor of the enzyme amadorase, lowers plasma 3-deoxyglucosone levels in diabetic rats | journal = Diabetes Technology & Therapeutics | volume = 3 | issue = 4 | pages = 609–16 | year = 2001 | pmid = 11911173 | doi = 10.1089/15209150152811234 }}</ref> |
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* Increased 3DG is correlated to increased ] ] width.<ref>{{cite journal | vauthors = Beisswenger PJ, Drummond KS, Nelson RG, Howell SK, Szwergold BS, Mauer M | title = Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress | journal = Diabetes | volume = 54 | issue = 11 | pages = 3274–81 | date = November 2005 | pmid = 16249455 | doi = 10.2337/diabetes.54.11.3274 | doi-access = free }}</ref> |
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* 3DG inactivates ].<ref>{{cite journal | vauthors = Takahashi M, Lu YB, Myint T, Fujii J, Wada Y, Taniguchi N | title = In vivo glycation of aldehyde reductase, a major 3-deoxyglucosone reducing enzyme: identification of glycation sites | journal = Biochemistry | volume = 34 | issue = 4 | pages = 1433–8 | date = January 1995 | pmid = 7827091 | doi = 10.1021/bi00004a038 }}</ref> Aldehyde reductase is the cellular enzyme that protects the body from 3DG. Detoxification of 3DG to 3-deoxyfructose (3DF) is impaired in diabetic humans since their ratio of 3DG to 3DF in urine and plasma differs significantly from non-diabetic individuals.<ref>{{cite journal | vauthors = Lal S, Kappler F, Walker M, Orchard TJ, Beisswenger PJ, Szwergold BS, Brown TR | title = Quantitation of 3-deoxyglucosone levels in human plasma | journal = Archives of Biochemistry and Biophysics | volume = 342 | issue = 2 | pages = 254–60 | date = June 1997 | pmid = 9186486 | doi = 10.1006/abbi.1997.0117 }}</ref> |
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* 3DG is a ] factor in diabetic embryopathy, leading to embryo malformation.<ref>{{cite journal | vauthors = Eriksson UJ, Wentzel P, Minhas HS, Thornalley PJ | title = Teratogenicity of 3-deoxyglucosone and diabetic embryopathy | journal = Diabetes | volume = 47 | issue = 12 | pages = 1960–6 | date = December 1998 | pmid = 9836531 | doi = 10.2337/diabetes.47.12.1960 }}</ref> This appears to arise from 3DG accumulation, which leads to superoxide-mediated embryopathy. Women with pre-existing diabetes or severe diabetes that develops during pregnancy are between 3 and 4 times more likely than other women to give birth to infants with birth defects. |
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* 3DG induces apoptosis in macrophage-derived cell lines<ref>{{cite journal | vauthors = Okado A, Kawasaki Y, Hasuike Y, Takahashi M, Teshima T, Fujii J, Taniguchi N | title = Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines | journal = Biochemical and Biophysical Research Communications | volume = 225 | issue = 1 | pages = 219–24 | date = August 1996 | pmid = 8769121 | doi = 10.1006/bbrc.1996.1157 }}</ref> and is toxic to cultured cortical neurons<ref>{{cite journal | vauthors = Kikuchi S, Shinpo K, Moriwaka F, Makita Z, Miyata T, Tashiro K | title = Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons: synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases | journal = Journal of Neuroscience Research | volume = 57 | issue = 2 | pages = 280–9 | date = July 1999 | pmid = 10398306 | doi = 10.1002/(SICI)1097-4547(19990715)57:2<280::AID-JNR14>3.0.CO;2-U | s2cid = 39613521 }}</ref> and PC12 cells.<ref>{{cite journal | vauthors = Suzuki K, Koh YH, Mizuno H, Hamaoka R, Taniguchi N | title = Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone | journal = Journal of Biochemistry | volume = 123 | issue = 2 | pages = 353–7 | date = February 1998 | pmid = 9538214 | doi = 10.1093/oxfordjournals.jbchem.a021944 }}</ref> |
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===3DG and ROS=== |
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3DG induces ] (ROS) that contribute to the development of diabetic complications.<ref>{{cite journal | vauthors = Araki A | title = | journal = Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics | volume = 34 | issue = 9 | pages = 716–20 | date = September 1997 | pmid = 9430981 }}</ref> Specifically, 3DG induces heparin-binding epidermal growth factor, a smooth muscle ] that is abundant in ] plaques. This observation suggests that an increase in 3DG may trigger atherogenesis in diabetes.<ref>{{cite journal | vauthors = Taniguchi N, Kaneto H, Asahi M, Takahashi M, Wenyi C, Higashiyama S, Fujii J, Suzuki K, Kayanoki Y | title = Involvement of glycation and oxidative stress in diabetic macroangiopathy | journal = Diabetes | volume = 45 | pages = S81-3 | date = July 1996 | issue = Suppl 3 | pmid = 8674900 | doi = 10.2337/diab.45.3.s81 | s2cid = 21268446 }}</ref><ref>{{cite journal | vauthors = Che W, Asahi M, Takahashi M, Kaneto H, Okado A, Higashiyama S, Taniguchi N | title = Selective induction of heparin-binding epidermal growth factor-like growth factor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes | journal = The Journal of Biological Chemistry | volume = 272 | issue = 29 | pages = 18453–9 | date = July 1997 | pmid = 9218489 | doi = 10.1074/jbc.272.29.18453 | doi-access = free }}</ref> 3DG also inactivates some enzymes that protect cells from ROS. For example, glutathione peroxidase, a central antioxidant enzyme that uses glutathione to remove ROS, and glutathione reductase, which regenerates glutathione, are both inactivated by 3DG.<ref>{{cite journal | vauthors = Vander Jagt DL, Hunsaker LA, Vander Jagt TJ, Gomez MS, Gonzales DM, Deck LM, Royer RE | title = Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes | journal = Biochemical Pharmacology | volume = 53 | issue = 8 | pages = 1133–40 | date = April 1997 | pmid = 9175718 | doi = 10.1016/S0006-2952(97)00090-7 }}</ref><ref>{{cite journal | vauthors = Niwa T, Tsukushi S | title = 3-deoxyglucosone and AGEs in uremic complications: inactivation of glutathione peroxidase by 3-deoxyglucosone | journal = Kidney International Supplements | volume = 78 | pages = S37-41 | date = February 2001 | pmid = 11168980 | doi = 10.1046/j.1523-1755.2001.59780037.x | doi-access = free }}</ref> Diabetic humans show increased oxidative stress.<ref>{{cite journal | vauthors = Feillet-Coudray C, Choné F, Michel F, Rock E, Thiéblot P, Rayssiguier Y, Tauveron I, Mazur A | title = Divergence in plasmatic and urinary isoprostane levels in type 2 diabetes | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 324 | issue = 1–2 | pages = 25–30 | date = October 2002 | pmid = 12204421 | doi = 10.1016/S0009-8981(02)00213-9 }}</ref> 3DG-induced ROS result in oxidative DNA damage.<ref>{{cite journal | vauthors = Shimoi K, Okitsu A, Green MH, Lowe JE, Ohta T, Kaji K, Terato H, Ide H, Kinae N | title = Oxidative DNA damage induced by high glucose and its suppression in human umbilical vein endothelial cells | journal = Mutation Research | volume = 480-481 | pages = 371–8 | date = September 2001 | pmid = 11506829 | doi = 10.1016/S0027-5107(01)00196-8 }}</ref> 3DG can be internalized by cells and internalized 3DG is responsible for the production of intracellular oxidative stress.<ref>{{cite journal | vauthors = Sakiyama H, Takahashi M, Yamamoto T, Teshima T, Lee SH, Miyamoto Y, Misonou Y, Taniguchi N | title = The internalization and metabolism of 3-deoxyglucosone in human umbilical vein endothelial cells | journal = Journal of Biochemistry | volume = 139 | issue = 2 | pages = 245–53 | date = February 2006 | pmid = 16452312 | doi = 10.1093/jb/mvj017 }}</ref> |
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===Detoxification=== |
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Although of uncertain medical significance, a variety of compounds react with 3DG, possibly deactivating it. One such agent is ] (AG).<ref>{{cite journal | vauthors = Brownlee M | title = Lilly Lecture 1993. Glycation and diabetic complications | journal = Diabetes | volume = 43 | issue = 6 | pages = 836–41 | date = June 1994 | pmid = 8194672 | doi = 10.2337/diab.43.6.836 | s2cid = 84490567 }}</ref> AG reduces AGE associated retinal, neural, arterial, and renal pathologies in animal models.<ref>{{cite journal | vauthors = Ellis EN, Good BH | title = Prevention of glomerular basement membrane thickening by aminoguanidine in experimental diabetes mellitus | journal = Metabolism | volume = 40 | issue = 10 | pages = 1016–9 | date = October 1991 | pmid = 1943726 | doi = 10.1016/0026-0495(91)90122-D }}</ref><ref>{{cite journal | vauthors = Soulis-Liparota T, Cooper M, Papazoglou D, Clarke B, Jerums G | title = Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat | journal = Diabetes | volume = 40 | issue = 10 | pages = 1328–34 | date = October 1991 | pmid = 1834497 | doi = 10.2337/diabetes.40.10.1328 }}</ref><ref>{{cite journal | vauthors = Edelstein D, Brownlee M | title = Aminoguanidine ameliorates albuminuria in diabetic hypertensive rats | journal = Diabetologia | volume = 35 | issue = 1 | pages = 96–7 | date = January 1992 | pmid = 1541387 | doi = 10.1007/BF00400859 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A | title = Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking | journal = Science | volume = 232 | issue = 4758 | pages = 1629–32 | date = June 1986 | pmid = 3487117 | doi = 10.1126/science.3487117 | bibcode = 1986Sci...232.1629B }}</ref> The problem with AG is that it is toxic in the quantities needed for efficacy.{{Cn|date=February 2021}} |
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==Additional reading== |
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*{{cite journal | vauthors = Delpierre G, Rider MH, Collard F, Stroobant V, Vanstapel F, Santos H, Van Schaftingen E | title = Identification, cloning, and heterologous expression of a mammalian fructosamine-3-kinase | journal = Diabetes | volume = 49 | issue = 10 | pages = 1627–34 | date = October 2000 | pmid = 11016445 | doi = 10.2337/diabetes.49.10.1627 }} |
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*{{cite book | vauthors = Baynes JW, Thorpe SR, Murtiashaw MH | title = Nonenzymatic glucosylation of lysine residues in albumin | chapter = [8] Nonenzymatic glucosylation of lysine residues in albumin | volume = 106 | pages = 88–98 | year = 1984 | pmid = 6436646 | doi = 10.1016/0076-6879(84)06010-9 | isbn = 978-0-12-182006-0 | series = Methods in Enzymology }} |
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*{{cite journal | vauthors = Dyer DG, Blackledge JA, Thorpe SR, Baynes JW | title = Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo | journal = The Journal of Biological Chemistry | volume = 266 | issue = 18 | pages = 11654–60 | date = June 1991 | doi = 10.1016/S0021-9258(18)99007-1 | pmid = 1904867 | doi-access = free }} |
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*{{cite journal | vauthors = Rahbar S, Kumar Yernini K, Scott S, Gonzales N, ] | title = Novel inhibitors of advanced glycation endproducts | journal = Biochemical and Biophysical Research Communications | volume = 262 | issue = 3 | pages = 651–6 | date = September 1999 | pmid = 10471380 | doi = 10.1006/bbrc.1999.1275 }} |
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*{{cite journal | vauthors = Yan SF, Ramasamy R, Naka Y, Schmidt AM | title = Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond | journal = Circulation Research | volume = 93 | issue = 12 | pages = 1159–69 | date = December 2003 | pmid = 14670831 | doi = 10.1161/01.RES.0000103862.26506.3D | doi-access = free }}* |
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==References== |
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{{Reflist|2}} |
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{{DEFAULTSORT:Deoxyglucosone, 3-}} |
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