Table 1

General overview of heme synthesis

STEP	DESCRIPTION	PORPHYRIA
1	Glycine + succinyl-coenzyme A → ΔALA Enzyme: ALA synthase Location: Mitochondria	Rate-limiting step in porphyrin synthesis
2	ΔALA + ΔALA → PBG Enzyme: ALA dehydratase Location: Cytosol	ADP
3	PBG → hydroxymethylbilane intermediate Enzyme: PBG deaminase Location: Cytosol	IAP
4	Hydroxymethylbilane intermediate → uroporphyrinogen III Enzyme: UROS Location: Cytosol	CEP
5	Uroporphyrinogen (uroporphyrinogen III or abnormal uroporphyrinogen I) → coproporphyrinogen III intermediate Enzyme: UROD Location: Cytosol	PCT
6	Coproporphyrinogen III intermediate → decarboxylation → protoporphyrinogen IX Enzyme: Coproporphyrinogen oxidase Location: Mitochondria	HCP
7	Protoporphyrinogen IX → protoporphyrin IX Enzyme: PPO Location: Mitochondria	VP
8	Protoporphyrin IX → heme synthesis Enzyme: Ferrochelatase Location: Mitochondria	EPP

ADP—ALA dehydratase deficiency porphyria, ALA—aminolevulinic acid, CEP— congenital erythropoietic porphyria, EPP—erythropoietic protoporphyria, HCP—hereditary coproporphyria, IAP— intermittent acute porphyria, PBG— porphobilinogen, PCT—porphyria cutanea tarda, PPO—protoporphyrinogen IX oxidase, UROD—uroporphyrinogen decarboxylase, UROS—uroporphyrinogen III synthase, VP—variegate porphyria.
Data from Sassa,¹ Puy et al,² Poblete-Gutiérrez et al,⁵ and Murphy.⁶