3-Deoxyglucosone

Last updated
3-Deoxyglucosone
3-Deoxyglucosone.svg
Names
IUPAC name
3-Deoxy-D-erythro-hexos-2-ulose
Systematic IUPAC name
(4S,5R)-4,5,6-Trihydroxy-2-oxohexanal
Other names
3-Deoxy-D-erythro-hexosulose; 2-Keto-3-deoxyglucose; 3-Deoxy-D-erythro-hexosulose; 3-Deoxy-D-glucosone; D-3-Deoxyglucosone
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.241.539 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C6H10O5/c7-2-4(9)1-5(10)6(11)3-8/h2,5-6,8,10-11H,1,3H2/t5-,6+/m0/s1 Yes check.svgY
    Key: ZGCHLOWZNKRZSN-NTSWFWBYSA-N Yes check.svgY
  • InChI=1/C6H10O5/c7-2-4(9)1-5(10)6(11)3-8/h2,5-6,8,10-11H,1,3H2/t5-,6+/m0/s1
    Key: ZGCHLOWZNKRZSN-NTSWFWBYBM
  • C(C(C(CO)O)O)C(=O)C=O
  • O=C(C=O)C[C@H](O)[C@H](O)CO
Properties
C6H10O5
Molar mass 162.141 g·mol−1
Density 1.406 g/ml
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

3-Deoxyglucosone (3DG) is a sugar that is notable because it is a marker for diabetes. 3DG reacts with protein to form advanced glycation end-products (AGEs), which contribute to diseases such as the vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, inflammation, and aging. [1]

Contents

Biosynthesis

4-Imidazolone arise from the condensation of arginine residues and 3-deoxyglucosone (R = CH2CH(OH)CH(OH)CH2OH). HydroimidazoloneAGE.png
4-Imidazolone arise from the condensation of arginine residues and 3-deoxyglucosone (R = CH2CH(OH)CH(OH)CH2OH).

3DG is made naturally via the Maillard reaction. 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 diabetes. Glucose reacts non-enzymatically with protein amino groups to initiate glycation. The formation of 3DG may account for the numerous complications of diabetes as well as aging. [1]

3DG arises also via the degradation of fructose 3-phosphate (F3P). [3] 3DG plays a central role in the development of diabetic complications via the action of fructosamine-3-kinase.[ citation needed ]

Biochemistry

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 advanced glycation end-products (AGEs). AGEs include imidazolones, pyrraline, N6-(carboxymethyl)lysine, and pentosidine. 3DG as well as AGEs play a role in the modification and cross-linking of long-lived proteins such as crystallin and collagen, contributing to diseases such as the vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, inflammation, and aging. [1]

3DG has a variety of potential biological effects, particularly when it is present at elevated concentrations in diabetic states:

3DG and ROS

3DG induces reactive oxygen species (ROS) that contribute to the development of diabetic complications. [14] Specifically, 3DG induces heparin-binding epidermal growth factor, a smooth muscle mitogen that is abundant in atherosclerotic plaques. This observation suggests that an increase in 3DG may trigger atherogenesis in diabetes. [15] [16] 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. [17] [18] Diabetic humans show increased oxidative stress. [19] 3DG-induced ROS result in oxidative DNA damage. [20] 3DG can be internalized by cells and internalized 3DG is responsible for the production of intracellular oxidative stress. [21]

Detoxification

Although of uncertain medical significance, a variety of compounds react with 3DG, possibly deactivating it. One such agent is aminoguanidine (AG). [22] AG reduces AGE associated retinal, neural, arterial, and renal pathologies in animal models. [23] [24] [25] [26] The problem with AG is that it is toxic in the quantities needed for efficacy.[ citation needed ]

Additional reading

Related Research Articles

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References

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  2. ↑ Bellier J, Nokin M, Lardé E, Karoyan P, Peulen O, Castronovo V, Bellahcène A (2019). "Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer". Diabetes Research and Clinical Practice. 148: 200–211. doi:10.1016/j.diabres.2019.01.002. PMID   30664892. S2CID   58631777.
  3. ↑ Szwergold BS, Kappler F, Brown TR (January 1990). "Identification of fructose 3-phosphate in the lens of diabetic rats". Science. 247 (4941): 451–4. Bibcode:1990Sci...247..451S. doi:10.1126/science.2300805. PMID   2300805.
  4. ↑ Kusunoki H, Miyata S, Ohara T, Liu BF, Uriuhara A, Kojima H, Suzuki K, Miyazaki H, Yamashita Y, Inaba K, Kasuga M (June 2003). "Relation between serum 3-deoxyglucosone and development of diabetic microangiopathy". Diabetes Care. 26 (6): 1889–94. doi: 10.2337/diacare.26.6.1889 . PMID   12766129.
  5. ↑ Wells-Knecht KJ, Lyons TJ, McCance DR, Thorpe SR, Feather MS, Baynes JW (September 1994). "3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes". Diabetes. 43 (9): 1152–6. doi:10.2337/diabetes.43.9.1152. PMID   8070616.
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  16. ↑ Che W, Asahi M, Takahashi M, Kaneto H, Okado A, Higashiyama S, Taniguchi N (July 1997). "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". The Journal of Biological Chemistry. 272 (29): 18453–9. doi: 10.1074/jbc.272.29.18453 . PMID   9218489.
  17. ↑ Vander Jagt DL, Hunsaker LA, Vander Jagt TJ, Gomez MS, Gonzales DM, Deck LM, Royer RE (April 1997). "Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes". Biochemical Pharmacology. 53 (8): 1133–40. doi:10.1016/S0006-2952(97)00090-7. PMID   9175718.
  18. ↑ Niwa T, Tsukushi S (February 2001). "3-deoxyglucosone and AGEs in uremic complications: inactivation of glutathione peroxidase by 3-deoxyglucosone". Kidney International Supplements. 78: S37-41. doi: 10.1046/j.1523-1755.2001.59780037.x . PMID   11168980.
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  20. ↑ Shimoi K, Okitsu A, Green MH, Lowe JE, Ohta T, Kaji K, Terato H, Ide H, Kinae N (September 2001). "Oxidative DNA damage induced by high glucose and its suppression in human umbilical vein endothelial cells". Mutation Research. 480–481: 371–8. doi:10.1016/S0027-5107(01)00196-8. PMID   11506829.
  21. ↑ Sakiyama H, Takahashi M, Yamamoto T, Teshima T, Lee SH, Miyamoto Y, Misonou Y, Taniguchi N (February 2006). "The internalization and metabolism of 3-deoxyglucosone in human umbilical vein endothelial cells". Journal of Biochemistry. 139 (2): 245–53. doi:10.1093/jb/mvj017. PMID   16452312.
  22. ↑ Brownlee M (June 1994). "Lilly Lecture 1993. Glycation and diabetic complications". Diabetes. 43 (6): 836–41. doi:10.2337/diab.43.6.836. PMID   8194672. S2CID   84490567.
  23. ↑ Ellis EN, Good BH (October 1991). "Prevention of glomerular basement membrane thickening by aminoguanidine in experimental diabetes mellitus". Metabolism. 40 (10): 1016–9. doi:10.1016/0026-0495(91)90122-D. PMID   1943726.
  24. ↑ Soulis-Liparota T, Cooper M, Papazoglou D, Clarke B, Jerums G (October 1991). "Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat". Diabetes. 40 (10): 1328–34. doi:10.2337/diabetes.40.10.1328. PMID   1834497.
  25. ↑ Edelstein D, Brownlee M (January 1992). "Aminoguanidine ameliorates albuminuria in diabetic hypertensive rats". Diabetologia. 35 (1): 96–7. doi: 10.1007/BF00400859 . PMID   1541387.
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