Coproporphyrinogen-III oxidase (CPOX) (CPOX)

Coproporphyrinogen-III oxidase (CPOX), also known as coproporphyrinogen dehydrogenase in its anaerobic forms, is a vital enzyme that catalyzes the sixth step of the heme biosynthetic pathway. In humans, this mitochondrial enzyme performs the oxidative decarboxylation of coproporphyrinogen III into protoporphyrinogen IX. A deficiency or mutation in the CPOX gene leads to Hereditary Coproporphyria (HCP), an autosomal dominant disorder characterized by the accumulation of toxic porphyrin precursors, resulting in neurological crises and skin photosensitivity. While humans utilize an oxygen-dependent version of the enzyme, many pathogenic bacteria and parasites, such as Staphylococcus aureus and Toxoplasma gondii, possess oxygen-independent variants (HemN) that utilize radical S-adenosylmethionine (SAM). This mechanistic divergence makes the dehydrogenase form a promising target for selective antimicrobial and antiparasitic drug development. Additionally, the enzyme's substrates, Coproporphyrin I and III, serve as critical endogenous biomarkers for assessing the inhibition of hepatic OATP1B1 and OATP1B3 transporters during clinical drug development, as their plasma levels reflect changes in transporter-mediated uptake and potential drug-drug interactions.

Other names

Coproporphyrinogen dehydrogenaseOxygen-independent coproporphyrinogen-III oxidaseHemNHemFCoproporphyrinogenaseOxygen-dependent coproporphyrinogen-III oxidase

Substrate-based replacement therapy to bypass enzyme deficiency; Non-competitive inhibition by heavy metals; Radical S-adenosylmethionine (SAM) mediated decarboxylation in anaerobic variants.