How seizure in children could be prevented from lysine catabolite accumulation
α-Aminoadipic semialdehyde dehydrogenase (ALDH7A1) is involved in lysine metabolism,.
The researchers show that ALDH7A1-deficient cells and mice accumulate lysine metabolites like piperideine-6-carboxylate (P6C) via the saccharopine pathway, which are thought to cause seizures in children with pyridoxine dependent epilepsy (PDE).
They explore two therapeutic strategies to reduce pathogenic lysine metabolite accumulation, including inhibiting lysine transport or enzymatically depleting lysine.
The authors develop a fluorescent biosensor to characterize lysine transporter activity and identify competitive substrates that reduce the accumulation of lysine catabolites in ALDH7A1-deficient cells. They also show that intravenous administration of lysine α-oxidase reduces lysine and P6C levels by >80% in mice.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01420-7
