delta-1-pyrroline-5-carboxylate synthase; P5CS; aldehyde dehydrogenase family 18 member A1; includes: glutamate 5-kinase; GK; gamma-glutamyl kinase; gamma-glutamyl phosphate reductase; GPR; glutamate-5-semialdehyde dehydrogenase; glutamyl-gamma-semialdehyde dehydrogenase (ALDH18A1, GSAS, P5CS, PYCS)

Function

• glutamate 5-kinase (gamma-glutamyl kinase)
• gamma-glutamylphosphate reductase (glutamate-5-semialdehyde dehydrogenase)
• amino-acid biosynthesis; L-proline biosynthesis; L-glutamate 5-semialdehyde from L-glutamate: step 1/2
• amino-acid biosynthesis; L-proline biosynthesis; L-glutamate 5-semialdehyde from L-glutamate: step 2/2

ATP + L-glutamate -> ADP + L-glutamate 5-phosphate.

L-glutamate 5-semialdehyde + phosphate + NADP(+) -> L-gamma-glutamyl 5-phosphate + NADPH

Inhibition:

• isoform short is inhibited by L-ornithine with a Ki of ~0.25 mM
• isoform long is insensitive to ornithine inhibition
  • this is due to the two amino acid insert which abolishes feedback inhibition of P5CS activity by L- ornithine

Structure

• in the N-terminal section; belongs to the glutamate-5-kinase family
• in the C-terminal section; belongs to the gamma-glutamyl phosphate reductase family

Compartment

• mitochondrial inner membrane

Alternative splicing

named isoforms=2; long, short

Pathology

• defects in ALDH18A1 are the cause of mental retardation-joint hypermobility-skin laxity with or without metabolic abnormalities
• defects in ALDH18A1 associated with De Barsy syndrome

More general terms

• kinase or ATP-phosphotransferase
• dehydrogenase
• mitochondrial protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5832
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5832
• OMIM: https://mirror.omim.org/entry/138250
• OMIM: https://mirror.omim.org/entry/612652
• UniProt: http://www.uniprot.org/uniprot/P54886.html