Aldehyde dehydrogenase 7A1 (ALDH7A1)

Aldehyde dehydrogenase 7A1 (ALDH7A1), also known as antiquitin, is a multifunctional enzyme primarily responsible for the catabolism of lysine via the pipecolic acid pathway [1, 4]. It catalyzes the oxidation of alpha-aminoadipic semialdehyde (alpha-AASA) to alpha-aminoadipate [3, 6]. Mutations in the ALDH7A1 gene cause a deficiency of this enzyme, leading to the accumulation of alpha-AASA and its cyclic form, delta1-piperideine-6-carboxylate (P6C), which chemically inactivate pyridoxal 5'-phosphate (PLP), the active form of vitamin B6 [1, 11]. This deficiency results in pyridoxine-dependent epilepsy (PDE), a rare neurometabolic disorder characterized by intractable seizures that respond to high doses of pyridoxine [2, 14]. Beyond its role in epilepsy, ALDH7A1 is involved in osmoregulation by converting betaine aldehyde to betaine and in the detoxification of reactive aldehydes generated by lipid peroxidation [4, 5]. In cancer research, ALDH7A1 is identified as a marker for cancer stem cells and is associated with chemoresistance and tumor progression, making it a potential target for novel oncology therapeutics [8, 26].

Other names

AntiquitinATQ1Alpha-aminoadipic semialdehyde dehydrogenaseP6c dehydrogenaseBetaine aldehyde dehydrogenaseEPDPDE

Substrate replacement and cofactor supplementation (Pyridoxine/PLP) to overcome secondary deficiency; competitive inhibition of lysine transport (Arginine) and dietary lysine restriction to reduce toxic metabolite accumulation [2, 3, 27].