4411 3-Hydroxyglutaric acid 3-Hydroxyglutaric acid is a member of the class of compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups. 3-Hydroxyglutaric acid is soluble (in water) and a weakly acidic compound (based on its pKa). When present in sufficiently high levels, 3-hydroxyglutaric acid can act as act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of 3-hydroxyglutaric acid are associated with glutaric aciduria type I (glutaric acidemia type I, glutaryl-CoA dehydrogenase deficiency, GA1, or GAT1). GA1 is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine and tryptophan. Excessive levels of their intermediate breakdown products (e.g. glutaric acid, glutaryl-CoA, 3-hydroxyglutaric acid, glutaconic acid) can accumulate and cause damage to the brain (and also other organs). Babies with glutaric acidemia type I are often born with unusually large heads (macrocephaly). Macrocephaly is amongst the earliest signs of GA1. GA1 also causes secondary carnitine deficiency because 3-hydroxyglutaric acid, like other organic acids, is detoxified by carnitine. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of untreated glutaric aciduria or glutaric acidemia. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures. It is believed that the excretion of 3-hydroxyglutaric acid is increased during ketosis, which occurs during glutaryl-CoA dehydrogenase deficiency. 638-18-6 181976 C5H8O5 White powder. No indication of carcinogenicity to humans (not listed by IARC). This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation. Chronically high levels of 3-hydroxyglutaric acid are associated with Glutaric Aciduria Type I. 2014-08-29T06:33:48Z 2018-03-21T17:46:19Z R-2-HYDROXYGLUTARATE DB04594 3HG true OC(CC(O)=O)CC(O)=O C5H8O5 InChI=1S/C5H8O5/c6-3(1-4(7)8)2-5(9)10/h3,6H,1-2H2,(H,7,8)(H,9,10) InChIKey=ZQHYXNSQOIDNTL-UHFFFAOYSA-N 148.114 148.037173366 Endogenous Solid HMDB00428 CHEMBL556937 158277