Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer's disease.

ABSTRACT: Emerging evidence suggests that sex-specific differences in L-serine (L-Ser) metabolism play a key role in Alzheimer's disease (AD). While disruptions in amino acid balance are well known, recent findings point to a dimorphic regulation of the serine biosynthetic pathway. To explore this, we examined post-translational modifications (PTMs) of D-3-phosphoglycerate dehydrogenase (PHGDH)-the rate-limiting enzyme for de novo L-Ser synthesis-as a potentialmechanism underlying this difference. PHGDH was immunoprecipitated from hippocampal tissue of healthy and AD-affected males and females and analyzed by mass spectrometry. Five phosphorylation sites (S55, T60, T78, S383, and S473) were shared across all groups, but a unique deacetylation at K289 appeared exclusively in AD males. Functional assa

SUBMITTER: Zerbini E 

PROVIDER: S-EPMC12917857 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature