ALDH7A1: Human aldehyde dehydrogenase 7A1
PDB Code: 2J6L
Human Aldehyde dehydrogenase 7A1 (ALDH7A1), also known as antiquitin, has recently been shown to be an important component of the lysine catabolic routes involving the L-pipecolic acid pathway. In this reaction sequence, ALDH7A1 catalyzes the final oxidation of α-aminoadipic semialdehyde to α-aminoadipate. The α-aminoadipic semialdehyde forms an intramolecular Schiff base resulting in L-Δ1-piperidine-6 carboxylate (P6C), and these two components are in an equilibrium in solution. P6C can act in a Knoevenagel condensation reaction with pyridoxal 5’phosphate, thus depleting the intracellular levels of this essential prosthetic group, which is involved among others in neurotransmitter metabolism. Through this mechanism the neurological symptoms observed in a rare neurological disorder are explained. Mutations in the ALDH7A1 gene (located on human chromosome 5q31) were recently shown to be involved in the pathophysiology of pyridoxine-dependent seizures (PDS). Classical PDS appears within four weeks of birth and can be treated by pyridoxine supplementation, however, ALDH7A1 deficiency with milder manifestations might be involved in thus far intractable forms of epilepsy.
ALDH7A1 is a member of the ALDH superfamily and shows the typical conserved sequence and active site features, and the mutations found in PDS map to several essential sites within the enzyme structure.

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