5-aminolevulinic acid dehydratase (ALAD)

5-aminolevulinic acid dehydratase (ALAD), also known as porphobilinogen synthase, is a critical zinc-dependent enzyme that catalyzes the second step of the heme biosynthetic pathway. It facilitates the condensation of two molecules of 5-aminolevulinic acid to form porphobilinogen, a precursor to heme, chlorophyll, and vitamin B12 (UniProt P13716). ALAD is highly sensitive to inhibition by heavy metals, particularly lead, which displaces the essential zinc ion from the enzyme's sulfhydryl groups, making erythrocyte ALAD activity a primary biomarker for lead exposure (NIH/PubChem). Genetic mutations in the ALAD gene lead to ALAD deficiency porphyria, a rare autosomal recessive metabolic disorder characterized by neurovisceral symptoms (StatPearls). In clinical practice, ALAD is also inhibited by succinylacetone in patients with Tyrosinemia Type I, leading to symptoms mimicking acute porphyria. Because of its central role in heme production and its extreme sensitivity to environmental toxins, ALAD is a significant target for toxicological monitoring and the study of metabolic anemias.

Other names

Porphobilinogen synthasePBGSDelta-aminolevulinic acid dehydrataseALA dehydratase

ALAD catalyzes the asymmetric condensation of two molecules of 5-aminolevulinic acid (ALA) to form the monopyrrole porphobilinogen (PBG), which is the second step in the heme biosynthetic pathway. Drugs or toxins targeting this enzyme typically act through competitive inhibition or by displacing the essential zinc cofactor from the enzyme's active site.