Heme biosynthesis (Rattus norvegicus)

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H+Fe2+Black - reactantsRed - side productsrate limiting stepprotoporphyrinogen IXAlas2O2H2Ocoproporphyrinogen IIIUrodCO2CoAFechglycineO2protohemeAladCO2CpoxPpoxH2Oprotoporphyrin IXporphobilinogenH2O2HmbsNH3H2OUroshydroxymethylbilaneALAS1succinyl-CoAdelta-aminolevulinateCO2Porphobilinogenuroporphyrinogen IIIdelta-aminolevulinate


Description

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

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP561(r21860) with a 53% conversion rate.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
116978view10:42, 16 May 2021EweitzModified title
107007view13:46, 17 September 2019MaintBotHMDB identifier normalization
89925view13:34, 6 October 2016MkutmonModified description
71829view19:35, 18 October 2013MaintBotremoved data source from nodes without identifier
70694view14:40, 28 August 2013EgonwAdded more ChemSpider IDs for metabolites previously only available as Label.
70005view23:32, 11 July 2013MaintBotupdated to 2013 schema
67336view10:39, 26 June 2013Christine ChichesterOntology Term : 'heme biosynthetic pathway' added !
41679view02:36, 2 March 2011MaintBotRemoved redundant pathway information and comments
35288view22:50, 11 February 2010Mills42Modified description
34069view19:09, 9 December 2009MaintBotAutomatic update of empty xrefs
33527view09:33, 1 December 2009MaintBotRemoved group label
30916view00:32, 30 July 2009MaintBotConverted from Homo sapiens
20861view11:30, 14 November 2008MaintBot[[Pathway:Rattus norvegicus:Heme Biosynthesis]] moved to [[Pathway:WP86]]: Moved to stable identifier
8136view13:46, 7 January 2008MaintBot[[Pathway:Rat:Heme Biosynthesis]] moved to [[Pathway:Rattus norvegicus:Heme Biosynthesis]]: Renaming species
7689view16:09, 18 December 2007MaintBotfixed category names
7374view12:42, 4 November 2007MaintBotAdded categories to GPML
6556view22:20, 22 May 2007Kdahlquistgpml file for [[Rat:Heme_Biosynthesis]]

External references

DataNodes

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NameTypeDatabase referenceComment
ALAS1GeneProduct65155 (Entrez Gene)
AladGeneProduct25374 (Entrez Gene)
Alas2GeneProduct25748 (Entrez Gene)
CO2MetaboliteHMDB0001967 (HMDB)
CoAMetaboliteHMDB0001423 (HMDB)
CpoxGeneProduct304024 (Entrez Gene)
FechGeneProduct361338 (Entrez Gene)
H2O2MetaboliteHMDB0003125 (HMDB)
H2OMetaboliteHMDB0002111 (HMDB)
HmbsGeneProduct25709 (Entrez Gene)
NH3MetaboliteHMDB0000051 (HMDB)
O2MetaboliteHMDB0001377 (HMDB)
PorphobilinogenMetaboliteHMDB0000245 (HMDB)
PpoxGeneProduct289219 (Entrez Gene)
UrodGeneProduct29421 (Entrez Gene)
UrosGeneProduct309070 (Entrez Gene)
coproporphyrinogen IIIMetabolite
delta-aminolevulinateMetabolite10447539 (Chemspider)
glycineMetabolite730 (Chemspider)
hydroxymethylbilaneMetabolite
porphobilinogenMetabolite
protohemeMetabolite
protoporphyrin IXMetabolite
succinyl-CoAMetabolite83179 (Chemspider)
uroporphyrinogen IIIMetabolite

Annotated Interactions

No annotated interactions
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