Heme Biosynthesis (Saccharomyces cerevisiae)

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protoporphyrinogen IXO22 H+Fe2+H2O2O23 porphobilinogens + H2Orate limiting stepRed - side productsCoA + CO22 CO22 H2OH2Odelta-aminolevulinate4 NH3Black - reactants4 CO2delta-aminolevulinatecoproporphyrinogen IIIHEM3HEM15HEM12HEM14porphobilinogenHEM1HEM13hydroxymethylbilaneprotoporphyrin IXHEM4uroporphyrinogen IIIprotohemeHEM2Succinyl-CoAGlycine


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 ╬┤ALA) 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

GenMAPP notes 

Based on Glycolysis and Gluconeogenesis Pathways at SGD and on Kruckeberg, AL and Dickinson, JR (2004) Carbon Metabolism in The Metabolism and Molecular Physiology of Saccharomyces cerevisiae, Dickinson, JR and Schweizer, M, eds, CRC Press.

GenMAPP remarks 

Richt click here for references

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Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
89926view13:34, 6 October 2016MkutmonModified description
72196view10:48, 27 October 2013EgonwMarked a bunch of Labels as Metabolite DataNodes.
69748view10:29, 11 July 2013EgonwMarked a few DataNodes with CAS registry numbers as metabolites.
67333view10:38, 26 June 2013Christine ChichesterOntology Term : 'heme biosynthetic pathway' added !
58991view19:39, 21 February 2013MaintBotUpdated Ensembl data source
41904view04:53, 2 March 2011MaintBotRemoved redundant pathway information and comments
35290view22:52, 11 February 2010Mills42Modified description
29882view11:09, 9 June 2009Thomasupdated ensembl references
20897view11:30, 14 November 2008MaintBot[[Pathway:Saccharomyces cerevisiae:Heme Biosynthesis]] moved to [[Pathway:WP102]]: Moved to stable identifier
12742view08:00, 17 May 2008MaintBotautomated metabolite conversion
10995view20:21, 2 March 2008MaintBotyeast id converter
8774view14:08, 7 January 2008MaintBotAdded to category $category
8772view14:08, 7 January 2008KdahlquistUploaded new pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2 CO2
2 H+
2 H2O
4 CO2
4 NH3
Fe2+
GlycineMetabolite
H2O
H2O2
HEM12GeneProductYDR047W (Ensembl)
HEM13GeneProductYDR044W (Ensembl)
HEM14GeneProductYER014W (Ensembl)
HEM15GeneProductYOR176W (Ensembl)
HEM1GeneProductYDR232W (Ensembl)
HEM2GeneProductYGL040C (Ensembl)
HEM3GeneProductYDL205C (Ensembl)
HEM4GeneProductYOR278W (Ensembl)
O2
Succinyl-CoAMetabolite
coproporphyrinogen IIIMetabolite2624-63-7 (CAS)
delta-aminolevulinate
hydroxymethylbilaneMetabolite73023-76-4 (CAS)
porphobilinogenMetabolite487-90-1 (CAS)
protohemeMetabolite14875-96-8 (CAS)
protoporphyrin IXMetabolite553-12-8 (CAS)
protoporphyrinogen IX
uroporphyrinogen IIIMetabolite1976-85-8 (CAS)

Annotated Interactions

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