Heme biosynthesis (WP561)

Homo sapiens

The enzymatic process that produces heme is properly called porphyrin synthesis, as all the intermediates are tetrapyrroles that are chemically classified are porphyrins. The process is highly conserved across biology. In humans, this pathway serves almost exclusively to form heme. In other species, it also produces similar substances such as cobalamin (vitamin B12). The pathway is initiated by the synthesis of D-Aminolevulinic acid (dALA or δALA) from the amino acid glycine and succinyl-CoA from the citric acid cycle (Krebs cycle). The rate-limiting enzyme responsible for this reaction, ALA synthase, is strictly regulated by intracellular iron levels and heme concentration. A low-iron level, e.g., in iron deficiency, leads to decreased porphyrin synthesis, which prevents accumulation of the toxic intermediates. This mechanism is of therapeutic importance: infusion of heme arginate or hematin can abort attacks of porphyria in patients with an inborn error of metabolism of this process, by reducing transcription of ALA synthase. The organs mainly involved in heme synthesis are the liver and the bone marrow, although every cell requires heme to function properly. Heme is seen as an intermediate molecule in catabolism of haemoglobin in the process of bilirubin metabolism. Source: Wikipedia http://en.wikipedia.org/wiki/Heme


Kdahlquist , Kristina Hanspers , Caroline Miller , Andra Waagmeester , Alex Pico , Egon Willighagen , Martina Summer-Kutmon , Denise Slenter , and Eric Weitz


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Homo sapiens



Pathway Ontology

heme biosynthetic pathway

Cell Type Ontology

hematopoietic cell bone marrow cell


Label Type Compact URI Comment
delta-aminolevulinate Metabolite chemspider:10447539
delta-aminolevulinate Metabolite chemspider:10447539
O2 Metabolite hmdb:HMDB0001377
porphobilinogen Metabolite cas:487-90-1
NH3 Metabolite hmdb:HMDB0000051
H+ Metabolite pubchem.compound:1038
H2O2 Metabolite hmdb:HMDB0003125
O2 Metabolite hmdb:HMDB0001377
CoA Metabolite hmdb:HMDB0001423
uroporphyrinogen III Metabolite cas:1976-85-8
CO2 Metabolite hmdb:HMDB0001967
succinyl-CoA Metabolite hmdb:HMDB0001022
Glycine Metabolite hmdb:HMDB0000123
H2O Metabolite hmdb:HMDB0002111 Type your comment here
coproporphyrinogen III Metabolite cas:2624-63-7
Porphobilinogen Metabolite hmdb:HMDB0000245
hydroxymethylbilane Metabolite chebi:16645
CO2 Metabolite hmdb:HMDB0001967
H2O Metabolite hmdb:HMDB0002111
Fe2+ Metabolite pubchem.compound:27284
H2O Metabolite hmdb:HMDB0002111
protoheme Metabolite cas:14875-96-8
CO2 Metabolite hmdb:HMDB0001967
protoporphyrin IX Metabolite cas:553-12-8
ALAS2 GeneProduct ncbigene:212
FECH GeneProduct ncbigene:2235
PPOX GeneProduct ncbigene:5498
CPOX GeneProduct ncbigene:1371
HMBS GeneProduct ncbigene:3145
ALAS1 GeneProduct ncbigene:211
ALAD GeneProduct ncbigene:210
UROS GeneProduct ncbigene:7390
UROD GeneProduct ncbigene:7389


  1. Heme biosynthesis pathway regulation in a model of hepatocarcinogenesis pre-initiation. Polo CF, Vazquez ES, Caballero F, Gerez E, Battle AM. Comp Biochem Physiol B. 1992 Sep;103(1):251–6. PubMed Europe PMC Scholia