Liver metabolism of porphyrins and haem

The liver is an active site for the biosynthesis of haem and porphyrinogens/porphyrins, which are intermediates of the haem biosynthetic pathway, because haem is required for functional activity of the cytochrome P 450 system and other critical hepatic haemoproteins. The production of hepatic haem is regulated primarily through the activity of aminolaevulinic acid synthase which is the first and normally rate-limiting enzyme of the pathway. This is, in turn, controlled by a putative regulatory haem pool. Hepatic haem can be repleted by the intravenous administration of haem, which is the basis for haem therapy in patients with acute porphyric attacks. The liver catabolizes haem to bilirubin through microsomal haem oxygenase activity and excretes haem into bile along with porphyrins. Biliary excretion of porphyrins increases significantly in patients with some types of porphyria. In protoporphyria this may cause liver damage as a result of protoporphyrin toxicity. The delineation of the pathway for protoporphyrin excretion into bile should facilitate therapy in protoporphyria by identifying ways in which protoporphyrin excretion can be enhanced.