Mannose-6-phosphate isomerase

Mannose-6-phosphate isomerase (MPI) is an isomerase that catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate, playing a critical role in supplying D-mannose derivatives required for eukaryotic glycosylation reactions (UniProt: P34949). The enzyme is essential for proper glycoprotein biosynthesis across multiple cellular processes and tissues.

Mutations in MPI cause congenital disorder of glycosylation type 1B (CDG1B), a multisystem disorder affecting nervous system development, motor function, and immune and coagulation systems due to impaired N-glycosylation (UniProt: P34949). This disease highlights the broad importance of proper glycoprotein synthesis during development and cellular maintenance.

MPI is upregulated in Alzheimer's disease brain tissue relative to age-matched controls, with a mean log2 fold-change of 0.77 across two subcellular fractions in post-mortem human brain analyzed by TMT-labeled quantitative proteomics (Chaparral AD proteomics). This upregulation may reflect altered glycosylation pathways or compensatory responses in the AD brain, though the functional significance requires further investigation.