Protoporphyrinogen oxidase

Protoporphyrinogen oxidase (PPO) is a heme biosynthesis enzyme that catalyzes the 6-electron oxidation of protoporphyrinogen-IX to protoporphyrin-IX (UniProt: P50336). The protein is essential for the final steps of heme production and is expressed primarily in hepatic and erythropoietic tissues where porphyrin metabolism occurs.

Mutations in PPOX cause variegate porphyria (VP), an autosomal dominant acute hepatic porphyria characterized by photosensitivity, skin manifestations, abdominal pain, and neuropsychiatric symptoms resulting from partial loss of enzyme activity (UniProt: P50336). A rare autosomal recessive form, childhood-onset variegate porphyria, presents with severe enzyme deficiency and early-onset symptoms including seizures and intellectual impairment.

Protoporphyrinogen oxidase is down-regulated in Alzheimer's Disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.26 in post-mortem AD brain proteomics (Chaparral AD proteomics). This modest reduction was detected via TMT-labeled quantitative mass spectrometry across subcellular fractions, suggesting a potential role for altered heme biosynthesis in AD pathology.