Heme Biosynthesis (Homo sapiens)

From WikiPathways

Jump to: navigation, search
1delta-aminolevulinaterate limiting stepdelta-aminolevulinateBlack - reactantsRed - side productsprotoporphyrinogen IXcoproporphyrinogen IIIH2OCoAFECHH2ONH3protohemeO2CPOXURODporphobilinogenUROSCO2protoporphyrin IXALAS2uroporphyrinogen IIIsuccinyl-CoAO2H2O2CO2PPOXPorphobilinogenALADH2OGlycineFe2+hydroxymethylbilaneALAS1HMBSH+CO2


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

Quality Tags

Ontology Terms



  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 PubMed Europe PMC Scholia


View all...
107186view14:27, 17 September 2019MaintBotChEBI identifier normalization
106818view13:29, 17 September 2019MaintBotHMDB identifier normalization
102939view09:48, 30 January 2019EgonwMade another label a Metabolite, and annotated with MIM some of the interaction (catalyses).
93014view15:05, 24 July 2017DeSlChanged (vague) CAS to ChEBI ID (which looked to be more relevant).
89918view13:32, 6 October 2016MkutmonModified description
72035view13:30, 24 October 2013Mkutmonfixed unconnected lines
70993view21:11, 21 September 2013EgonwConverted two metabolites from Label to Metabolite.
70636view09:52, 20 August 2013EgonwConverted a combined label into a DataNode.
70635view09:46, 20 August 2013EgonwConverted a IUPAC-named Label into a Chemspider-backed Metabolite DataNode.
70093view18:34, 12 July 2013MaintBotupdating to 2013 schema
45350view20:27, 7 October 2011AlexanderPicoOntology Term : 'hematopoietic cell' added !
45349view20:26, 7 October 2011AlexanderPicoOntology Term : 'bone marrow cell' added !
45347view20:25, 7 October 2011AlexanderPicoOntology Term : 'heme biosynthetic pathway' added !
41027view23:13, 1 March 2011MaintBotRemoved redundant pathway information and comments
38913view20:50, 24 September 2010Khanspers
37761view18:57, 1 July 2010KhanspersChanged representation of enzymes
35633view19:10, 12 February 2010AndraAdded references
35284view22:46, 11 February 2010Mills42Modified description
34432view18:14, 10 December 2009MaintBotAutomatic update of empty xrefs
32151view14:01, 14 August 2009MaintBotFixed group labels
21860view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:Heme Biosynthesis]] moved to [[Pathway:WP561]]: Moved to stable identifier
15407view23:07, 27 May 2008Khanspersconnectors fix
14725view21:51, 23 May 2008Khansperstest
14721view21:47, 23 May 2008KhanspersRemoved stochiometry
14524view01:31, 23 May 2008KhanspersAdded metabolites
14519view01:24, 23 May 2008KhanspersAdded connectors, metabolites
14508view01:14, 23 May 2008KhanspersPeriodical save, work in progress
13079view11:14, 17 May 2008MaintBotautomated metabolite conversion
8132view13:46, 7 January 2008MaintBot[[Pathway:Human:Heme Biosynthesis]] moved to [[Pathway:Homo sapiens:Heme Biosynthesis]]: Renaming species
7687view16:09, 18 December 2007MaintBotfixed category names
7372view12:42, 4 November 2007MaintBotAdded categories to GPML
6332view22:17, 22 May 2007Kdahlquistgpml file for [[Human:Heme_Biosynthesis]]

External references


View all...
NameTypeDatabase referenceComment
ALADGeneProduct210 (Entrez Gene)
ALAS1GeneProduct211 (Entrez Gene)
ALAS2GeneProduct212 (Entrez Gene)
CO2MetaboliteHMDB0001967 (HMDB)
CPOXGeneProduct1371 (Entrez Gene)
CoAMetaboliteHMDB0001423 (HMDB)
FECHGeneProduct2235 (Entrez Gene)
Fe2+Metabolite27284 (PubChem-compound)
GlycineMetaboliteHMDB0000123 (HMDB)
H+Metabolite1038 (PubChem-compound)
H2O2MetaboliteHMDB0003125 (HMDB)
H2OMetaboliteHMDB0002111 (HMDB)
HMBSGeneProduct3145 (Entrez Gene)
NH3MetaboliteHMDB0000051 (HMDB)
O2MetaboliteHMDB0001377 (HMDB)
PPOXGeneProduct5498 (Entrez Gene)
PorphobilinogenMetaboliteHMDB0000245 (HMDB)
URODGeneProduct7389 (Entrez Gene)
UROSGeneProduct7390 (Entrez Gene)
coproporphyrinogen IIIMetabolite2624-63-7 (CAS)
delta-aminolevulinateMetabolite10447539 (Chemspider)
hydroxymethylbilaneMetaboliteCHEBI:16645 (ChEBI)
porphobilinogenMetabolite487-90-1 (CAS)
protohemeMetabolite14875-96-8 (CAS)
protoporphyrin IXMetabolite553-12-8 (CAS)
protoporphyrinogen IXMetabolite
succinyl-CoAMetaboliteHMDB0001022 (HMDB)
uroporphyrinogen IIIMetabolite1976-85-8 (CAS)

Annotated Interactions

No annotated interactions

Personal tools