Leloir pathway

The Leloir pathway is the primary metabolic route for the catabolism of D-galactose into glucose-1-phosphate, which subsequently enters the glycolytic cycle for energy production [1][2]. This pathway is mediated by a sequence of three essential enzymes: galactokinase (GALK1), galactose-1-phosphate uridylyltransferase (GALT), and UDP-galactose 4-epimerase (GALE) [2][3]. Genetic deficiencies in any of these enzymes result in galactosemia, a group of rare inherited metabolic disorders [1]. Classic galactosemia (Type I), caused by GALT deficiency, is the most severe form and leads to the toxic accumulation of galactose-1-phosphate, which can cause liver failure, cataracts, and intellectual disabilities [1][4]. While the standard of care is a lifelong galactose-restricted diet, pharmacological interventions are being developed to target the pathway, including GALK1 inhibitors to prevent toxic intermediate formation and aldose reductase inhibitors to reduce the production of galactitol [5][6].

Other names

Galactose metabolic pathwayD-galactose catabolic pathwayGalactose-to-glucose conversion pathway

Substrate reduction therapy via inhibition of galactokinase (GALK1) to prevent the formation of toxic galactose-1-phosphate, or inhibition of the alternative polyol pathway via aldose reductase to prevent the accumulation of galactitol [5][6].