Chemical Structures of Porphyrins and Related Compoundsâ
Haem Synthesis |
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| A molecule of ALA is formed by the condensation of glycine and succinyl-coA (not shown). This is catalysed by the enzymeALA synthase, which is vitally important as its activity controls the rate at which porphyrins and haem are synthesised. It is the controlling enzyme of the pathway. | |
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5-aminolaevulinic acid (ALA) |
| Two molecules of ALA combine to form a monopyrrole—the five-sided ring in the centre of PBG. This is catalysed by the enzyme ALA dehydratase, which is defective in ALA dehydratase porphyria. | |
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Porphobilinogen (PBG) |
| Four molecules of PBG combine to form a linear tetrapyrrole—four monopyrroles strung together end to end. This step is catalysed by the enzymehydroxymethylbilane synthase (also known as PBG deaminase), which is defective in acute intermittent porphyria (AIP). | |
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Hydroxymethylbilane |
| The open section on the left of the structure above - where two pyrrole rings lie adjacent to each other but not joined—is then closed, producing a tetrapyrrole ring. This produces the first porphyrin on the pathway, uroporphyrinogen. This step is catalysed by uroporphyrinogen lll cosynthase, which also tweaks the ring into a particular orientation called the lll isomer. This enzyme is defective incongenital erythropoietic protoporphyria. | |
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Uroporphyrinogen lll |
| Four of the carboxylic acid side chains (COOH) are successively knocked off by the enzyme uroporphyrinogen decarboxylase (UROD), producing the heptacarboxylic, hexacarboxylic and pentacarboxylic porphyrinogen intermediates (not shown), ending in coproporphyrinogen lll. This enzyme is defective inporphyria cutanea tarda (PCT). | |
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Coproporphyrinogen lll |
| A further two carboxylic acid side chains are knocked off by the enzymecoproporphyrinogen oxidase, which is defective in hereditary coproporphyria(HCP). | |
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Protoporphyrinogen lX |
| This molecule is then oxidised from protoporphyrinogen lX to protoporphyrin lX by the enzyme protoporphyrinogen oxidase, which is defective in variegate porphyria. | |
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Protoporphyrin lX |
| An iron atom (Fe2+) is inserted into the centre of the tetrapyrrole ring to form haem. This is catalysed by the enzyme ferrochelatase, which is defective inerythropoietic protoporphyria. | |
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Haem |
Haem Breakdown |
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| The tetrapyrrole ring is broken open (See the gap between the O atoms at the top of the structure below). This step is catalysed by the enzyme haem oxygenase. | |
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Biliverdin |
| This is further reduced to bilirubin by the enzyme biliverdin reductase | |
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Bilirubin |
| Bilirubin is the form in which the breakdown products of haem are excreted from the body: in the bowel, it is further broken down to urobilinogen and stercobilinogen by bacteria. | |
Acknowledgement: All images retrieved from the Kyoto Encyclopedia of Genes and Genomes via the DBGET database system.