PPOX

PPOX, in a biomedical context, refers to the gene and the protein protoporphyrinogen oxidase. This mitochondrial enzyme is encoded by the PPOX gene in humans and other organisms, and it catalyzes a key oxidative step in heme biosynthesis: the conversion of protoporphyrinogen IX to protoporphyrin IX. The enzyme participates in the later stages of the tetrapyrrole pathway, just before the insertion of iron to form heme.

Functionally, protoporphyrinogen oxidase is a flavin-dependent oxidase located in the mitochondria, where it uses molecular oxygen to oxidize protoporphyrinogen IX to protoporphyrin IX. The resulting protoporphyrin IX is then converted to heme by ferrochelatase. Proper activity of PPOX is essential for efficient heme production in erythroid cells and other tissues.

Genetically, pathogenic variants in PPOX are associated with variegate porphyria (VP), an autosomal dominant porphyria with incomplete penetrance and variable expressivity. VP arises from partial deficiency of PPOX, leading to accumulation of porphyrin precursors that can cause cutaneous photosensitivity and acute neurovisceral symptoms. Environmental triggers such as sunlight exposure, certain medications, alcohol, and fasting can provoke attacks in susceptible individuals.

Diagnosis combines biochemical testing and genetic analysis. Elevated porphyrin metabolites in urine or feces can indicate VP, and sequencing of the PPOX gene can identify disease-causing variants. Management focuses on avoiding known triggers, treating acute attacks with standard porphyria protocols such as hemin therapy when indicated, and providing symptomatic care.