galactokinase

Galactokinase is a cytosolic enzyme that catalyzes the first phosphorylation step in the Leloir pathway of galactose metabolism. It transfers a phosphate group from ATP to galactose, producing galactose-1-phosphate and ADP, with Mg2+ as a typical cofactor. In humans, the enzyme is encoded by the GALK1 gene.

The reaction can be summarized as: galactose + ATP → galactose-1-phosphate + ADP. After formation, galactose-1-phosphate enters further processing by the enzymes of the Leloir pathway, including galactose-1-phosphate uridylyltransferase and UDP-glucose 4-epimerase, to generate nucleotide sugars required for glycoprotein and glycolipid synthesis and to support galactose utilization.

Clinical significance: Deficiency of galactokinase (GALK1 deficiency) is a form of galactosemia. It leads to impaired phosphorylation of galactose, resulting in elevated levels of galactose and its reduction product galactitol, which can accumulate in the lens and cause infantile or early childhood cataracts. Other organ systems are usually less affected than in some other forms of galactosemia, but symptoms can vary. Diagnosis is based on biochemical testing showing elevated galactose (and galactitol) in blood or urine, with genetic testing confirming GALK1 mutations. Management typically involves dietary galactose restriction to prevent cataract development and other galactose-related complications.

Galactokinase is conserved across many organisms and functions within the broader network of carbohydrate metabolism, linking sugar uptake to downstream pathways that supply essential monosaccharide nucleotides for biosynthesis.