D-galactose dehydrogenase (GaDH)

D-galactose dehydrogenase (GaDH) is an oxidoreductase enzyme (EC 1.1.1.48) that catalyzes the conversion of D-galactose to D-galactono-1,4-lactone using NAD+ or NADP+ as a cofactor [1, 13]. While primarily known for its role in the bacterial De Ley-Doudoroff pathway, GaDH activity is also found in mammalian tissues, including the human liver, where it provides an alternative oxidative route for galactose metabolism [7, 19]. This pathway is particularly relevant in patients with classic galactosemia, as it allows for the conversion of excess galactose into galactonate, which can be further metabolized or excreted [20, 22]. Although GaDH is not a primary target for therapeutic drug development, it is widely employed as a highly specific analytical reagent in clinical diagnostics to measure galactose and lactose levels in blood and food [1, 18]. Furthermore, the enzyme is a subject of interest in research involving D-galactose-induced aging models, which are used to study oxidative stress and neurodegeneration [3, 23]. In these models, chronic administration of the substrate D-galactose leads to the accumulation of metabolic byproducts that mimic natural aging processes [4, 8]. Recent studies also suggest a potential role for the enzyme's product, galactonate, in the pathogenesis of urolithiasis through its interaction with the gut microbiome [25]. Overall, GaDH serves as a vital metabolic enzyme and a robust diagnostic tool rather than a direct site for pharmacological intervention [1, 10].

Other names

D-galactose:NAD+ 1-oxidoreductasebeta-galactose dehydrogenaseNAD+-dependent D-galactose dehydrogenaseGalactose 1-dehydrogenase

Competitive inhibition of substrate binding; Irreversible inactivation of catalytic residues; Mimicry of carbohydrate substrates [10].