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Pathway Description
Metabolism and Physiological Effects of Oxalic acid
Homo sapiens
Metabolic Pathway
Oxalic acid (oxalate) is a strong dicarboxylic acid that is also a known uremic toxin. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. Glyoxylate is generated through glycine and hydroxyproline catabolism and can be converted to oxalate. In humans, this process takes place in the liver. Glycine and hydroxyproline comes from protein sources in the diet such as red meat and eggs. Glycine Is converted into glyoxylate in the peroxisome by the enzyme d-amino acid oxidase. Proline is converted to hydroxyproline in the endoplasmic reticulum using the enzyme prolyl 4-hydroxylase. The hydroxyproline metabolism to glyoxylate occurs in the mitochondria. Hydroxyproline dehydrogenase converts hydroxyproline to pyrroline hydroxycarboxylic acid. Delta-1-pyrroline-5-carboxylate dehydrogenase then catalyzes the formation of 4-hydroxy-L-glutamic acid from pyrroline hydroxycarboxylic acid. 4-hydroxy-2-oxoglutaric acid is then produced from 4-hydroxy-L-glutamic acid using the enzyme aspartate aminotransferase. Finally, 4-hydroxy-L-glutamic acid is converted to glyoxylate using 4-hydroxy-2-oxoglutarate aldolase. The glyoxylate formed enters the cytosol. in the cytosol, glyoxylate is converted oxalate using lactate dehydrogenase.
Unused ascorbic acid can be also used to synthesize oxalate in the body. Although the specific reactions and enzymes involved are still unknown, there is a general sense of what metabolites are formed during oxalate synthesis from ascorbic acid. Ascorbic acid forms dehydroascorbic acid, which then forms 2,3-diketo-L-gulonate. 2,3-diketo-L-gulonate can be converted to oxalate. The oxalate formed in the liver form these 3 sources can enter the blood and have toxic effects in other tissues. Oxalate can promote cardiovascular disease, neurotoxicity and inflammation.
References
Metabolism and Physiological Effects of Oxalic acid References
Baker PR, Cramer SD, Kennedy M, Assimos DG, Holmes RP: Glycolate and glyoxylate metabolism in HepG2 cells. Am J Physiol Cell Physiol. 2004 Nov;287(5):C1359-65. doi: 10.1152/ajpcell.00238.2004. Epub 2004 Jul 7.
Pubmed: 15240345
Knight J, Madduma-Liyanage K, Mobley JA, Assimos DG, Holmes RP: Ascorbic acid intake and oxalate synthesis. Urolithiasis. 2016 Aug;44(4):289-97. doi: 10.1007/s00240-016-0868-7. Epub 2016 Mar 22.
Pubmed: 27002809
Wu, G., Bazer, F.W., Burghardt, R.C., Johnson, G.A., Kim, S.W., Knabe, D.A., Li, P., Li, X., McKnight, J.R., Satterfield, M.C., & Spencer, T.E. (2010). Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids, 40, 1053-1063.
Rivas CI, Zuniga FA, Salas-Burgos A, Mardones L, Ormazabal V, Vera JC: Vitamin C transporters. J Physiol Biochem. 2008 Dec;64(4):357-75. doi: 10.1007/BF03174092.
Pubmed: 19391462
Huang, Y., Zhang, Y. H., Chi, Z. P., Huang, R., Huang, H., Liu, G. Y., Zhang, Y. F., Yang, H. S., Lin, J. H., Yang, T. H., & Cao, S. Z. (2019). The handling of oxalate in the body and the origin of oxalate in calcium oxalate stones. Urologia Internationalis, 104(3-4), 167–176. https://doi.org/10.1159/000504417
Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vazquez-Fresno R, Sajed T, Johnson D, Li C, Karu N, Sayeeda Z, Lo E, Assempour N, Berjanskii M, Singhal S, Arndt D, Liang Y, Badran H, Grant J, Serra-Cayuela A, Liu Y, Mandal R, Neveu V, Pon A, Knox C, Wilson M, Manach C, Scalbert A: HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D608-D617. doi: 10.1093/nar/gkx1089.
Pubmed: 29140435
Martens M, Ammar A, Riutta A, Waagmeester A, Slenter DN, Hanspers K, A Miller R, Digles D, Lopes EN, Ehrhart F, Dupuis LJ, Winckers LA, Coort SL, Willighagen EL, Evelo CT, Pico AR, Kutmon M: WikiPathways: connecting communities. Nucleic Acids Res. 2021 Jan 8;49(D1):D613-D621. doi: 10.1093/nar/gkaa1024.
Pubmed: 33211851
Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M: KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551. doi: 10.1093/nar/gkaa970.
Pubmed: 33125081
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