Heme biosynthesis (WP561)

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
last edited


Kdahlquist, MaintBot, Khanspers, Mills42, Andra, AlexanderPico, Egonw, Mkutmon, DeSl, and Eweitz

Cited In


Homo sapiens



Pathway Ontology: heme biosynthetic pathway

Cell Type Ontology: bone marrow cell hematopoietic cell


Label Type Compact Identifier
protoporphyrinogen IX Metabolite None
delta-aminolevulinate Metabolite chemspider:10447539
delta-aminolevulinate Metabolite chemspider:10447539
ALAS2 GeneProduct ncbigene:212
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
FECH GeneProduct ncbigene:2235
CoA Metabolite hmdb:HMDB0001423
PPOX GeneProduct ncbigene:5498
uroporphyrinogen III Metabolite cas:1976-85-8
CO2 Metabolite hmdb:HMDB0001967
succinyl-CoA Metabolite hmdb:HMDB0001022
CPOX GeneProduct ncbigene:1371
Glycine Metabolite hmdb:HMDB0000123
H2O Metabolite hmdb:HMDB0002111
HMBS GeneProduct ncbigene:3145
coproporphyrinogen III Metabolite cas:2624-63-7
Porphobilinogen Metabolite hmdb:HMDB0000245
hydroxymethylbilane Metabolite chebi:16645
CO2 Metabolite hmdb:HMDB0001967
ALAS1 GeneProduct ncbigene:211
ALAD GeneProduct ncbigene:210
H2O Metabolite hmdb:HMDB0002111
UROS GeneProduct ncbigene:7390
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
UROD GeneProduct ncbigene:7389


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