Delta-aminolevulinic acid dehydratase

Delta-aminolevulinic acid dehydratase (ALAD) is a pyrrole biosynthesis enzyme that catalyzes an early step in heme tetrapyrrole synthesis by condensing two 5-aminolevulinate molecules to form porphobilinogen (UniProt: P13716). The protein functions as a key metabolic node linking amino acid catabolism to essential cofactor production.

ALAD is primarily expressed in hepatic tissues where it participates in the heme biosynthetic pathway. Mutations in ALAD cause acute hepatic porphyria (AHEPP), a rare inherited disorder characterized by accumulation of porphyrin precursors and acute neurovisceral attacks triggered by drugs, infections, or metabolic stress (UniProt: P13716).

In Alzheimer's disease, ALAD shows ambiguous regulation across subcellular fractions in post-mortem AD brain tissue relative to age-matched controls, with a mean log2 fold-change of 0.098 (Chaparral AD proteomics). The modest and inconsistent direction across fractions suggests no clear net dysregulation of this protein in AD pathology, though its role in cellular bioenergetics warrants continued investigation in neurodegenerative contexts.