Pterin-4-alpha-carbinolamine Dehydratase (PCBD1)

PCBD1, also known as pterin-4-alpha-carbinolamine dehydratase or PHS, is a 104-amino acid protein (UniProt: P61457) that catalyzes a key step in tetrahydrobiopterin (BH4) biosynthesis by preventing 7-pterin formation and accelerating quinonoid-BH2 production. Beyond its enzymatic role, it functions as a coactivator for HNF1A and HNF1B-dependent transcription, regulating homeodomain protein dimerization and enhancing transcriptional activity (UniProt: P61457).

PCBD1 mutations cause hyperphenylalaninemia, BH4-deficient type D (HPABH4D; MIM 264070), an autosomal recessive disorder characterized by primapterinuria and abnormal pterin metabolism, presenting with mild neurologic signs including hypotonia and delayed motor development (UniProt: P61457).

PCBD1 is upregulated in Alzheimer's disease brain tissue. Quantitative proteomics analysis of post-mortem AD brain compared to age-matched controls detected a mean log2 fold-change of +0.57 across examined subcellular fractions (Chaparral AD proteomics). This elevation suggests a potential role in AD-associated pathophysiology, though the specific mechanistic contribution remains to be elucidated.