Phosphoserine phosphatase

Phosphoserine phosphatase (PSPH) is a 225-amino-acid enzyme that catalyzes the final irreversible step in L-serine biosynthesis from carbohydrates, converting O-phospho-L-serine to L-serine (UniProt: P78330). The product serine serves multiple metabolic roles including protein synthesis, amino acid production, nucleotide metabolism, and glutathione synthesis. Notably, L-serine can be racemized to D-serine, which functions as a neuromodulator in the central nervous system.

PSPH is broadly relevant to amino acid metabolism and neuronal function. Deficiency of this enzyme causes an autosomal recessive disorder (MIM 614023) characterized by growth retardation, psychomotor impairment, and facial dysmorphology, highlighting its developmental importance. The enzyme's role in serine availability positions it at a critical junction for multiple biosynthetic pathways essential to neuronal health.

In Alzheimer's disease, PSPH protein levels are significantly elevated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of +0.42 across examined subcellular fractions. This upregulation may reflect altered amino acid metabolism or compensatory responses to neurodegeneration-associated metabolic stress in AD pathology.