Transaldolase

Transaldolase (TALDO1) is a metabolic enzyme that catalyzes the rate-limiting step of the non-oxidative pentose phosphate pathway, reversibly converting sedheptulose-7-phosphate and glyceraldehyde 3-phosphate into erythrose-4-phosphate and fructose 6-phosphate (UniProt: P37837). Beyond its classical role in carbohydrate metabolism, the enzyme modulates other metabolic pathways through dynamic subcellular localization between nucleus and cytoplasm, suggesting pleiotropic metabolic functions.

Transaldolase deficiency (TALDOD, MIM 606003) is a recognized inborn error of the pentose phosphate pathway causing multisystem disease with growth retardation, dysmorphic features, hepatosplenomegaly, and hematologic complications (UniProt: P37837). These clinical features underscore the metabolic importance of pentose phosphate pathway integrity in development and systemic homeostasis.

In Alzheimer's disease, transaldolase expression is significantly reduced in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change −0.79, Chaparral AD proteomics). This downregulation may reflect compromised pentose phosphate pathway flux and altered metabolic capacity in AD neurodegeneration, potentially affecting both biosynthetic capacity and NADPH-dependent antioxidant defenses in affected neurons.