Glukoosi6fosfataasien

Glukoosi6fosfataasien, known in English as glucose‑6‑phosphate dehydrogenase (G6PD), is an essential enzyme in the pentose phosphate pathway. It catalyzes the first and rate‑limiting step of the pathway, converting glucose‑6‑phosphate into 6‑phosphoglucono‑δ‑lactone while reducing nicotinamide adenine dinucleotide phosphate (NADP^+) to NADPH. NADPH is vital for reductive biosynthetic reactions and for maintaining the cellular antioxidant system through the regeneration of reduced glutathione.

The enzyme is a homodimer composed of two identical subunits, each containing a Rossmann fold for NADP^+ binding and an active site that coordinates the substrate. G6PD activity is regulated by allosteric modulators, substrate concentration, and post‑translational modifications such as phosphorylation. It is expressed in almost all tissues, with high activity in the liver, kidney, and erythrocytes.

Clinically, deficiency of G6PD is one of the most common enzymopathies worldwide. Mutations in the G6PD gene lead to a spectrum of clinical manifestations, ranging from asymptomatic hemolytic anemia triggered by oxidative stress to chronic nonspherocytic hemolytic anemia. Newborns with severe deficiency may develop neonatal jaundice. Diagnosis is typically made by measuring enzyme activity in red blood cells and confirmed with molecular testing. Treatment involves avoidance of oxidative drugs (e.g., primaquine, sulfa drugs) and supportive care during hemolytic episodes.

Research into G6PD has implications beyond anemia, including identification of its role in cancer cell metabolism, the immune response, and neurodegeneration. The enzyme remains a target for therapeutic modulation, with interest in developing specific inhibitors for treating certain malignancies and agents that modulate NADPH production in metabolic disorders.