The structure of glyoxylic acid is shown as having an aldehydefunctional group. The aldehyde is only a minor component of the form most prevalent in some situations. Instead, glyoxalic acid often exists as a hydrate or a cyclic dimer. For example, in the presence of water, the carbonyl rapidly converts to a geminal diol (described as the "monohydrate"). The equilibrium constant (K) is 300 for the formation of dihydroxyacetic acid at room temperature:[5] Dihydroxyacetic acid has been characterized by X-ray crystallography.[6]
In aqueous solution, this monohydrate exists in equilibrium with a hemiacylal dimer form:[7]
In isolation, the aldehyde structure has as a major conformer a cyclic hydrogen-bonded structure with the aldehyde carbonyl in close proximity to the carboxyl hydrogen:[8]
The Henry's law constant of glyoxylic acid is KH = 1.09 × 104 × exp[(40.0 × 103/R) × (1/T − 1/298)].[9]
The conjugate base of glyoxylic acid is known as glyoxylate and is the form that the compound exists in solution at neutral pH. Glyoxylate is the byproduct of the amidation process in biosynthesis of several amidated peptides.
For the historical record, glyoxylic acid was prepared from oxalic acid electrosynthetically:[10][11] in organic synthesis, lead dioxide cathodes were applied for preparing glyoxylic acid from oxalic acid in a sulfuric acid electrolyte.[12]
Hot nitric acid can oxidizeglyoxal to glyoxylic; however this reaction is highly exothermic and prone to thermal runaway. In addition, oxalic acid is the main side product.
Glyoxylate is an intermediate of the glyoxylate cycle, which enables organisms, such as bacteria,[13] fungi, and plants [14] to convert fatty acids into carbohydrates. The glyoxylate cycle is also important for induction of plant defense mechanisms in response to fungi.[15] The glyoxylate cycle is initiated through the activity of isocitrate lyase, which converts isocitrate into glyoxylate and succinate. Research is being done to co-opt the pathway for a variety of uses such as the biosynthesis of succinate.[16]
Glyoxylate is produced via two pathways: through the oxidation of glycolate in peroxisomes or through the catabolism of hydroxyproline in mitochondria.[17] In the peroxisomes, glyoxylate is converted into glycine by AGT1 or into oxalate by glycolate oxidase. In the mitochondria, glyoxylate is converted into glycine by AGT2 or into glycolate by glyoxylate reductase. A small amount of glyoxylate is converted into oxalate by cytoplasmic lactate dehydrogenase.[18]
Oxalate and glyoxylate metabolism in hepatocytes. AGT1 and 2, alanine:glyoxylate aminotransferase 1 and 2; GO, glycolate oxidase; GR, glyoxylate reductase; HKGA, 4-hydroxy-2-ketoglutarate lyase; LDH, lactate dehydrogenase
In addition to being an intermediate in the glyoxylate cycle, glyoxylate is also an important intermediate in the photorespiration pathway. Photorespiration is a result of the side reaction of RuBisCO with O2 instead of CO2. While at first considered a waste of energy and resources, photorespiration has been shown to be an important method of regenerating carbon and CO2, removing toxic phosphoglycolate, and initiating defense mechanisms.[19][20] In photorespiration, glyoxylate is converted from glycolate through the activity of glycolate oxidase in the peroxisome. It is then converted into glycine through parallel actions by SGAT and GGAT, which is then transported into the mitochondria.[21][20] It has also been reported that the pyruvate dehydrogenase complex may play a role in glycolate and glyoxylate metabolism.[22]
Glyoxylate is thought to be a potential early marker for Type II diabetes.[23] One of the key conditions of diabetes pathology is the production of advanced glycation end-products (AGEs) caused by the hyperglycemia.[24] AGEs can lead to further complications of diabetes, such as tissue damage and cardiovascular disease.[25] They are generally formed from reactive aldehydes, such as those present on reducing sugars and alpha-oxoaldehydes. In a study, glyoxylate levels were found to be significantly increased in patients who were later diagnosed with Type II diabetes.[23] The elevated levels were found sometimes up to three years before the diagnosis, demonstrating the potential role for glyoxylate to be an early predictive marker.
Glyoxylate is involved in the development of hyperoxaluria, a key cause of nephrolithiasis (commonly known as kidney stones). Glyoxylate is both a substrate and inductor of sulfate anion transporter-1 (sat-1), a gene responsible for oxalate transportation, allowing it to increase sat-1 mRNA expression and as a result oxalate efflux from the cell. The increased oxalate release allows the buildup of calcium oxalate in the urine, and thus the eventual formation of kidney stones.[18]
The disruption of glyoxylate metabolism provides an additional mechanism of hyperoxaluria development. Loss of function mutations in the HOGA1 gene leads to a loss of the 4-hydroxy-2-oxoglutarate aldolase, an enzyme in the hydroxyproline to glyoxylate pathway. The glyoxylate resulting from this pathway is normally stored away to prevent oxidation to oxalate in the cytosol. The disrupted pathway, however, causes a buildup of 4-hydroxy-2-oxoglutarate which can also be transported to the cytosol and converted into glyoxylate through a different aldolase. These glyoxylate molecules can be oxidized into oxalate increasing its concentration and causing hyperoxaluria.[17]
Glyoxylic acid is one of several ketone- and aldehyde-containing carboxylic acids that together are abundant in secondary organic aerosols. In the presence of water and sunlight, glyoxylic acid can undergo photochemical oxidation. Several different reaction pathways can ensue, leading to various other carboxylic acid and aldehyde products.[29]
^pKa Data Compiled by R. Williams, "Archived copy"(PDF). Archived from the original(PDF) on 2010-06-02. Retrieved 2010-06-02.{{cite web}}: CS1 maint: archived copy as title (link).
^Holms WH (1987). "Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli". Biochem Soc Symp. 54: 17–31. PMID3332993.
^Escher CL, Widmer F (1997). "Lipid mobilization and gluconeogenesis in plants: do glyoxylate cycle enzyme activities constitute a real cycle? A hypothesis". Biol. Chem. 378 (8): 803–813. PMID9377475.
^Dubey, Mukesh K.; Broberg, Anders; Sooriyaarachchi, Sanjeewani; Ubhayasekera, Wimal; Jensen, Dan Funck; Karlsson, Magnus (September 2013). "The glyoxylate cycle is involved in pleotropic phenotypes, antagonism and induction of plant defence responses in the fungal biocontrol agent Trichoderma atroviride". Fungal Genetics and Biology. 58–59: 33–41. doi:10.1016/j.fgb.2013.06.008. ISSN1087-1845. PMID23850601.
^Zhu, Li-Wen; Li, Xiao-Hong; Zhang, Lei; Li, Hong-Mei; Liu, Jian-Hua; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Jie (November 2013). "Activation of glyoxylate pathway without the activation of its related gene in succinate-producing engineered Escherichia coli". Metabolic Engineering. 20: 9–19. doi:10.1016/j.ymben.2013.07.004. ISSN1096-7176. PMID23876414.
^ abSchnedler, Nina; Burckhardt, Gerhard; Burckhardt, Birgitta C. (March 2011). "Glyoxylate is a substrate of the sulfate-oxalate exchanger, sat-1, and increases its expression in HepG2 cells". Journal of Hepatology. 54 (3): 513–520. doi:10.1016/j.jhep.2010.07.036. ISSN0168-8278. PMID21093948.
^Zhang, Zhisheng; Mao, Xingxue; Ou, Juanying; Ye, Nenghui; Zhang, Jianhua; Peng, Xinxiang (January 2015). "Distinct photorespiratory reactions are preferentially catalyzed by glutamate:glyoxylate and serine:glyoxylate aminotransferases in rice". Journal of Photochemistry and Photobiology B: Biology. 142: 110–117. doi:10.1016/j.jphotobiol.2014.11.009. ISSN1011-1344. PMID25528301.
^Blume, Christian; Behrens, Christof; Eubel, Holger; Braun, Hans-Peter; Peterhansel, Christoph (November 2013). "A possible role for the chloroplast pyruvate dehydrogenase complex in plant glycolate and glyoxylate metabolism". Phytochemistry. 95: 168–176. Bibcode:2013PChem..95..168B. doi:10.1016/j.phytochem.2013.07.009. ISSN0031-9422. PMID23916564.
