Glucose-6-phosphate-dehydrogenase

Glucose-6-phosphate dehydrogenase

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that plays a critical role in the pentose phosphate pathway, a metabolic pathway parallel to glycolysis. This enzyme is crucial for cellular redox homeostasis and the production of NADPH, which is essential for biosynthetic reactions and the maintenance of reduced glutathione levels in cells.

Function

G6PD catalyzes the first step in the pentose phosphate pathway, converting glucose-6-phosphate into 6-phosphoglucono-δ-lactone while reducing NADP+ to NADPH. This reaction is vital for cells to generate NADPH, which is used in various anabolic reactions, including fatty acid synthesis and the detoxification of reactive oxygen species.

Clinical Significance

G6PD deficiency is a genetic disorder that affects the red blood cells, leading to a condition known as hemolytic anemia. This deficiency is the most common enzyme deficiency worldwide, affecting over 400 million people. It is particularly prevalent in regions where malaria is endemic, as the deficiency provides some protection against the malaria parasite.

Symptoms

Individuals with G6PD deficiency may experience symptoms such as jaundice, dark urine, fatigue, and rapid heart rate, especially after exposure to certain triggers like infections, certain foods (e.g., fava beans), and medications (e.g., sulfonamides, aspirin).

Diagnosis

Diagnosis of G6PD deficiency is typically made through a blood test that measures the activity of the G6PD enzyme. Genetic testing can also be used to identify specific mutations in the G6PD gene.

Management

Management of G6PD deficiency involves avoiding known triggers and managing symptoms of hemolytic anemia. In severe cases, blood transfusions may be necessary.

Genetics

The G6PD gene is located on the X chromosome, which means that G6PD deficiency is an X-linked recessive condition. This explains why the condition is more common in males, who have only one X chromosome, compared to females, who have two.

Evolutionary Perspective

The prevalence of G6PD deficiency in malaria-endemic regions is an example of balancing selection, where the protective effect against malaria outweighs the disadvantages of the deficiency.

Also see

• Pentose phosphate pathway
• NADPH
• Hemolytic anemia
• X-linked recessive inheritance
• Malaria