Delta-aminolevulinic acid dehydratase (ALAD) (ALAD)

Delta-aminolevulinic acid dehydratase (ALAD), also known as porphobilinogen synthase, is a critical cytosolic enzyme in the heme biosynthetic pathway. It catalyzes the second step of the pathway: the asymmetric condensation of two molecules of delta-aminolevulinic acid (ALA) to form porphobilinogen (PBG), the precursor to all biological tetrapyrroles including heme and chlorophyll. ALAD is a zinc-dependent enzyme that functions as a homooctamer and is a classic example of a morpheein protein, capable of shifting between different oligomeric states. The enzyme is exceptionally sensitive to inhibition by lead, which displaces the essential zinc ion, leading to the accumulation of ALA—a neurotoxin that acts as a GABA receptor agonist. This inhibition is a primary mechanism of lead poisoning, resulting in anemia and neurological damage. Hereditary deficiency of ALAD causes ALAD deficiency porphyria (ADP), an extremely rare and severe metabolic disorder. Clinically, ALAD activity and ALA levels are used as diagnostic biomarkers for lead exposure and certain hereditary diseases.

Other names

Porphobilinogen synthasePBGS5-aminolevulinate dehydrataseALA dehydrataseALADH

Inhibition of enzymatic activity through displacement of essential zinc cofactors or competitive binding at the active site.