Glutaric acid

Glutaric acid is a simple five-carbon linear dicarboxylic acid. Glutaric acid is naturally produced in the body during the metabolism of some amino acids including lysine and tryptophan. Glutaric acid may cause irritation to the skin and eyes. When present in sufficiently high levels glutaric acid can 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 glutaric acid are associated with at least three inborn errors of metabolism including glutaric aciduria type I malonyl-CoA decarboxylase deficiency and glutaric aciduria type III. Glutaric aciduria type I (glutaric acidemia type I glutaryl-CoA dehydrogenase deficiency GA1 or GAT1) is an inherited disorder in which the body is unable to completely break down the amino acids lysine hydroxylysine and tryptophan due to a deficiency of mitochondrial glutaryl-CoA dehydrogenase (EC 1.3.99.7 GCDH) . 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 glutaric 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.