GALT

GALT encodes galactose-1-phosphate uridylyltransferase, a homodimeric HIT protein superfamily enzyme that catalyzes the second Leloir pathway step, converting galactose-1-phosphate and UDP-glucose into glucose-1-phosphate and UDP-galactose^[1]. Mechanistically, GALT acts after GALM and GALK1 and before GALE, placing it at the central transferase step of galactose metabolism^[1][2]. GALT deficiency causes classic galactosemia, a neonatal metabolic disease that can present as life-threatening illness and remains associated with long-term cognitive, social, and reproductive complications despite dietary galactose restriction^[3]. In disease models, GALT-deficient mice showed absent GALT activity, reduced litter size, delayed pregnancy, and growth restriction, supporting their use for pathogenesis and therapy studies^[4]. Compared with related Leloir enzymes, GALT differs from ATP-dependent GALK1 and SDR-family GALE because it functions as a HIT-family uridylyltransferase with a His-Pro-His active-site motif^[1]. Compared with Duarte GALT variants, classic galactosemia shows very low residual GALT activity, whereas Duarte alleles retain partial enzyme function^[1][3]. For experimental applications, mutant GALT studies link enzymatic impairment to altered substrate binding, thermal stability, and folding, supporting pharmacological chaperones and proteostasis regulators as research directions^[5].- GALT defines the HIT-family transferase step connecting galactose-1-phosphate clearance with UDP-galactose production^[1].- Classic galactosemia models support mechanistic studies of fertility, growth, neurological outcomes, and therapy^[3][4].- Mutant GALT folding assays provide practical tools for evaluating chaperone-based rescue strategies^[5].