Lactaldehyde dehydrogenase (ALDH7A1) (ALDH7A1)

Lactaldehyde dehydrogenase, primarily known as ALDH7A1 or Antiquitin in humans, is a multifunctional enzyme within the aldehyde dehydrogenase superfamily that is essential for the catabolism of lysine [1][2]. It catalyzes the NAD+-dependent oxidation of alpha-aminoadipic semialdehyde (alpha-AASA) to alpha-aminoadipate and is also involved in the metabolism of lactaldehyde and the detoxification of reactive aldehydes produced during lipid peroxidation [1][3]. Mutations in the ALDH7A1 gene cause Pyridoxine-dependent epilepsy (PDE), a rare disorder where the accumulation of piperideine-6-carboxylate (P6C) leads to the chemical inactivation of pyridoxal 5'-phosphate (PLP), the active form of Vitamin B6 [4][5]. This deficiency results in severe, neonatal-onset seizures that are typically resistant to standard anticonvulsants but respond dramatically to pharmacological doses of pyridoxine [5][6]. Beyond its role in epilepsy, ALDH7A1 is implicated in cellular protection against osmotic and oxidative stress, and its upregulation in certain cancers has been linked to increased cell survival and resistance to chemotherapy [3][7]. Current therapeutic management focuses on lifelong pyridoxine supplementation, often combined with a lysine-restricted diet and arginine supplementation to reduce the production of toxic upstream metabolites [5][8].

Other names

AntiquitinATQ1Aldehyde dehydrogenase family 7 member A1Alpha-aminoadipic semialdehyde dehydrogenaseP6C dehydrogenase2,6-dimethyl-5-heptenal dehydrogenase

Cofactor supplementation to restore pyridoxal 5'-phosphate levels and substrate reduction therapy to minimize the accumulation of neurotoxic metabolites.