Heme biosynthesis (WP18)

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, M.Braymer, Khanspers, Mills42, Christine Chichester, Mkutmon, DeSl, and Eweitz

Cited In


Mus musculus



Pathway Ontology: heme biosynthetic pathway


Label Type Compact Identifier
Alas2 GeneProduct ncbigene:11656
O2 Metabolite hmdb:HMDB0001377
Porphobilinogen Metabolite cas:487-90-1
NH3 Metabolite hmdb:HMDB0000051
H2O2 Metabolite hmdb:HMDB0003125
O2 Metabolite hmdb:HMDB0001377
Fech GeneProduct ncbigene:14151
CoA Metabolite hmdb:HMDB0001423
Ppox GeneProduct ncbigene:19044
Uroporphyrinogen III Metabolite cas:1976-85-8
CO2 Metabolite hmdb:HMDB0001967
Cpox GeneProduct ncbigene:12892
H2O Metabolite hmdb:HMDB0002111
Hmbs GeneProduct ncbigene:15288
Coproporphyrinogen III Metabolite cas:2624-63-7
Porphobilinogen Metabolite cas:487-90-1
Hydroxymethylbilane Metabolite chebi:16645
CO2 Metabolite hmdb:HMDB0001967
Alas1 GeneProduct ncbigene:11655
Alad GeneProduct ncbigene:17025
H2O Metabolite hmdb:HMDB0002111
Uros GeneProduct ncbigene:22276
H2O Metabolite hmdb:HMDB0002111
protoheme Metabolite cas:14875-96-8
CO2 Metabolite hmdb:HMDB0001967
Protoporphyrin IX Metabolite cas:553-12-8
Urod GeneProduct ncbigene:22275