Transketolase

Transketolase (TKT, encoded by the TKT gene) is a thiamine pyrophosphate-dependent enzyme that catalyzes the reversible transfer of two-carbon ketol groups between ketose and aldose substrates, playing a central role in the non-oxidative pentose phosphate pathway and carbohydrate metabolism (UniProt: P29401). The protein is broadly expressed across tissues and participates in both energy metabolism and biosynthetic pathways requiring ribose-5-phosphate and NADPH. Pathogenic variants in TKT cause short stature, developmental delay, and congenital heart defects (SDDHD, MIM 617044), an autosomal recessive syndrome often accompanied by intellectual disability and ocular complications (UniProt: P29401).

In Alzheimer's disease, transketolase is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.84 across two subcellular fractions (Chaparral AD proteomics). This elevation was detected via TMT-labeled tandem mass spectrometry across four subcellular compartments (P2, P3, S2, S3) from human brain homogenates. The upregulation may reflect compensatory metabolic activity or altered glucose metabolism in AD pathology, though the specific functional consequences remain to be determined.