Porphobilinogen deaminase

Porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase, is an enzyme involved in the heme biosynthesis pathway. It plays a crucial role in the conversion of porphobilinogen (PBG) to hydroxymethylbilane (HMB), which is a key step in the synthesis of heme, an essential molecule for various biological processes.

Function

PBGD is responsible for catalyzing the removal of the amino group from PBG, resulting in the formation of HMB. This enzymatic reaction is a critical step in the biosynthesis of heme, a molecule that is essential for the function of hemoglobin, myoglobin, and various cytochromes involved in oxygen transport and energy production.

Structure

PBGD is a cytoplasmic enzyme that belongs to the family of pyridoxal 5'-phosphate (PLP)-dependent enzymes. It consists of a single polypeptide chain with a molecular weight of approximately 40 kDa. The enzyme contains a PLP cofactor, which is essential for its catalytic activity.

Clinical Significance

Mutations in the PBGD gene can lead to a rare genetic disorder known as acute intermittent porphyria (AIP). AIP is characterized by the accumulation of porphyrin precursors, including PBG, in the body. This can result in a wide range of symptoms, including abdominal pain, neurological disturbances, and skin sensitivity to sunlight.

Diagnosis and Treatment

The diagnosis of AIP involves measuring the levels of porphyrin precursors in the urine and genetic testing to identify mutations in the PBGD gene. Treatment of AIP mainly focuses on managing symptoms and preventing acute attacks. This may involve avoiding triggers such as certain medications, maintaining a healthy lifestyle, and using medications to control symptoms during acute attacks.

See Also

• Heme biosynthesis
• Acute intermittent porphyria