Delta-1-pyrroline-5-carboxylate synthase (P5CS)

Delta-1-pyrroline-5-carboxylate synthase (P5CS), encoded by the ALDH18A1 gene, is a bifunctional mitochondrial enzyme of the aldehyde dehydrogenase family responsible for catalyzing the first steps of proline, ornithine, and arginine biosynthesis from glutamate[1][3][7]. P5CS activity is essential for cellular protein production, collagen and elastin synthesis, and maintenance of energy metabolism within mitochondria. Mutations in ALDH18A1 disrupt amino acid synthesis and mitochondrial function, causing diseases such as hereditary spastic paraplegia types 9A and 9B (SPG9A/SPG9B), cutis laxa (skin laxity and connective tissue abnormalities), developmental delay, intellectual disability, cataracts, and neurological degeneration. Clinical presentation varies, potentially involving lower limb spasticity, cognitive impairment, joint hyperlaxity, and vision abnormalities[1][2][3][6][7]. As of current research, no pharmaceuticals directly target this enzyme, and therapy remains based on managing symptoms of the associated diseases.

Other names

ALDH18A1Aldehyde dehydrogenase 18 family member A1Glutamate 5-kinaseGamma-glutamyl phosphate reductaseGSASPYCSGKGPRGlutamate-5-semialdehyde dehydrogenaseGlutamyl-gamma-semialdehyde dehydrogenaseADCL3ARCL3ASPG9SPG9ASPG9B

Not applicable (no direct inhibitors or activators in clinical use)