protein
Delta-aminolevulinic acid dehydratase
aka ALADH
Gene
ALAD
Organism
Homo sapiens(9606)
Length
330 aa
Mass
36,295 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
⚠ Ambiguous — detected in AD samples, direction unclear across fractionsP3
-0.628
P2
not detected
S2
+0.825
S3
not detected
Mean log₂FC across detected fractions: +0.0982 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen
Disease associations
Acute hepatic porphyriaAHEPP
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.
Sources
Last updated 5/8/2026, 6:34:46 AM