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: 1) glutamate 5-kinase (gamma-glutamyl kinase) 2) gamma-glutamylphosphate reductase (glutamate-5-semialdehyde dehydrogenase) 3) amino-acid biosynthesis; L-proline biosynthesis; L-glutamate 5-semialdehyde from L-glutamate: step 1/2 4) 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

General

dehydrogenase kinase or ATP-phosphotransferase mitochondrial protein

Properties

SIZE: entity length = 795 aa MW = 87 kD COMPARTMENT: mitochondria MOTIF: Glutamate 5-kinase {1-361} Gamma-glutamyl phosphate reductase {362-795}

Database Correlations

OMIM correlations MORBIDMAP 138250 UniProt P54886 PFAM correlations Entrez Gene 5832 Kegg hsa:5832 ENZYME correlations

References

UniProt :accession P54886