 | |
| Names | |
|---|---|
| Preferred IUPAC name Oxiranecarboxamide | |
| Other names Glycidic acid amide Oxirane-2-carboxamide | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider | |
| ECHA InfoCard | 100.024.694 |
| UNII | |
| |
| |
| Properties | |
| C3H5NO2 | |
| Molar mass | 87.078 g·mol−1 |
| Density | 1.404 g/cm3[1] |
| Melting point | 32–34 °C (90–93 °F; 305–307 K) |
| Pharmacology | |
| Pharmacokinetics: | |
| 5 hours | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Glycidamide is anorganic compound with the formula H2NC(O)C2H3O. It is a colorless oil. Structurally, it contains adjacentamides andepoxidefunctional groups. It is a bioactive, potentially toxic or even carcinogenic metabolite ofacrylonitrile andacrylamide.[2][3] It is a chiral molecule.
Glycidamide is a reactiveepoxide metabolite from acrylamide[4][5] and can react withnucleophiles. This results in covalent binding of theelectrophile.[6]
Glycidamide gives a positive response in theAmes/Salmonella mutagenicity assay, which indicates that it can cause mutations in theDNA.[4] However, "Epidemiologic studies of workers for possible health effects from exposures to acrylamide have not shown a consistent increase in cancer risk."[7]
Early studies showed that glycidamides can be synthesized by the action ofhydrogen peroxide on acrylonitrile derivatives.[8]
More relevant to health concerns, glycidamide forms fromacrylamide. The acrylamide is generated by pyrolysis of proteins rich inasparagine. Oxidation of acrylamide, catalyzed by the enzymecytochrome P450 2E1 (CYP2E1) gives glycidamide.[9]Saturated fatty acids protect the acrylamide from forming glycidamide. When during food processing, oil is used that contains unsaturated fatty acids, the amount of glycidamide formed is much higher.[10]
Glycidamide reacts with DNA to form adducts. It is more reactive toward DNA than acrylamide. Several glycidamide-DNA adducts have been characterized. The main DNA adducts are N7-(2-carbamoyl-2-hydroxyethyl)-guanine (or N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (or N3-GA-Ade).[7] Glycidamide also reacts with haemoglobine (Hb) to form acysteineadduct, S-(20hydroxy-2carboxyethyl)cysteine.[6] With this reaction, N-terminal valine adducts are also formed.[11]
According to a major review, acrylamide "is extensively metabolized, mostly by conjugation withglutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of acrylamide. The reaction of glycidamide and glutathione represents a detoxification pathway."[12][5][13]
Glycidamide inhibits the sodium/potassium ATPase protein present in the plasma membrane of nerve cells.[14] Intracellular sodium increases and intracellular potassium decreases due to this inhibition. This causesdepolarization of the nerve membrane. The depolarization triggers a reverse sodium/calcium exchange, which will cause calcium-mediated axon degeneration.[15]
The liver is a very active organ in themetabolism ofxenobiotics. Substances in the liver modify the compounds to make them more soluble in water, in order to excrete them throughbile andurine. In the case of acrylamide, this metabolic strategy result in a greatertoxicity of the compound.[16] Whether this is the case for glycidamide remains unclear.
Glycidamide can be detoxified through diverse pathways such as the formation of glycidamide-glutathione conjugates. Both an enzymatic pathway via glutathione-S-transferase and a non-enzymatic pathway exist. These glycidamide-glutathione conjugates are further metabolized to mercapturic acids by variouspeptidases andtransferases, such as gamma-glutamyl-transpeptidase, dipeptidase, and N-acetyltransferase. The mercapturic acids that can be formed are N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) (Huang et al., 2011). These mercapturic acids are excreted through urine.[13]
Glycidamide can also behydrolyzed to glyceramide both spontaneously or enzymatically by microsomal epoxide hydrolase.[13] This too can be excreted through urine.[6]
Mice and rats show mutations and DNA adducts consistent with those arising from glycidamide.[9][17][18] Another study found tumors in the mice bodies after treatment with glycidamide[19] A study byNational Toxicology Program (2014)[20] provided evidence of carcinogenic activity of glycidamide in several species of rats and mice. For two years, rats and mice were exposed to varying doses of glycidamide in drinking water. In the rats and mice were several carcinogenic effects found, such ascarcinomas,fibroadenomas and malignant mesotheliomas.
