Delta-aminolevulinic acid dehydratase

Delta-aminolevulinic acid dehydratase

Structure of Delta-aminolevulinic acid dehydratase

Delta-aminolevulinic acid dehydratase (ALAD) is an enzyme that plays a crucial role in the biosynthesis of heme, a vital component of hemoglobin and other hemoproteins. It catalyzes the second step in the heme synthesis pathway, converting delta-aminolevulinic acid (ALA) into porphobilinogen (PBG). ALAD is found in various tissues, including the liver, bone marrow, and red blood cells.

Structure

The structure of ALAD consists of eight identical subunits, forming a symmetrical octamer. Each subunit contains a catalytic site responsible for the enzymatic activity. The enzyme is highly conserved across species, indicating its importance in biological processes.

Function

ALAD is a key enzyme in the heme biosynthesis pathway. It catalyzes the condensation of two molecules of ALA to form PBG. This reaction is essential for the subsequent steps in heme synthesis. ALAD is regulated by feedback inhibition, where heme acts as a negative regulator, controlling the rate of heme production.

Clinical Significance

Mutations in the ALAD gene can lead to a rare genetic disorder called ALAD deficiency porphyria (ADP). ADP is characterized by the accumulation of ALA and PBG, resulting in symptoms such as abdominal pain, neurological disturbances, and skin photosensitivity. Diagnosis of ADP is typically done through genetic testing and measurement of ALAD activity.

Role in Lead Poisoning

ALAD is also known for its role in lead poisoning. Lead inhibits ALAD activity, leading to the accumulation of ALA in the body. This can result in a condition known as lead-induced porphyria, which shares some symptoms with ADP. Measurement of ALAD activity is used as a biomarker for lead exposure and toxicity.

See Also

• Heme
• Porphobilinogen
• Lead poisoning
• Porphyria