Creatine pathway (Homo sapiens)

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Non-enzymatic conversionCreatine uptake:Mainly brain, muscleCreatine synthesis:Kidney, Liver, Pancreas, BrainOrnithine aminotransferase deficiencyArginine/glycineamidinotransferasedeficiencyCreatinetransporterdeficiencyUrinary creatinine excretionGuanidinoacetate methyltransferase deficiencycreatinineGlutamate-5-semialdehydeADPPhospho-guanidinoacetateGuanidinoacetateS-adenosylmethionineGlycinecreatinineArginineS-AdenosylhomocysteineSLC6A8Pyrroline-5-carboxylateglutamateATPADPprolineORNITHINECreatineCKCreatineVitamin B6PhosphocreatineGATMGAMTOATATP2-oxoglutarateCK


Description

In humans, creatine is synthesized in the liver, pancreas, kidney and brain. From arginine and glycine, guanidinoacetate and ornithine are formed. With S-adenosylmethionine and the help of GAMT, guanidinoacetate is converted into creatine. From the liver, pancreas, kidney and brain, creatine is exported to tissues such as skeletal muscle and brain, where it undergoes phosphorylation and serves as a short-term energy store. Creatine is transported to mainly the brain and muscles with the help of SLC6A8 transporter.

Once formed, phosphocreatine and creatine undergo both a slow spontaneous reaction to form creatinine, which is excreted from the body via the urinary system.

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Quality Tags

Ontology Terms

 

Bibliography

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  1. Atherton RS, Laws JF, Miles BJ, Thomson AR; ''Brain adenosine 5'-triphosphate-creatine phosphotransferase.''; Biochem J, 1970 PubMed Europe PMC Scholia
  2. Pemberton TA, Tanner JJ; ''Structural basis of substrate selectivity of Δ(1)-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): semialdehyde chain length.''; Arch Biochem Biophys, 2013 PubMed Europe PMC Scholia
  3. Rossi JJ, Vender J, Berg CM, Coleman WH; ''Partial purification and some properties of delta1-pyrroline-5-carboxylate reductase from Escherichia coli.''; J Bacteriol, 1977 PubMed Europe PMC Scholia
  4. Sekhar PN, Amrutha RN, Sangam S, Verma DP, Kishor PB; ''Biochemical characterization, homology modeling and docking studies of ornithine delta-aminotransferase--an important enzyme in proline biosynthesis of plants.''; J Mol Graph Model, 2007 PubMed Europe PMC Scholia
  5. HOBSON GE, REES KR; ''The annelid phosphokinases.''; Biochem J, 1957 PubMed Europe PMC Scholia
  6. Komoto J, Huang Y, Takata Y, Yamada T, Konishi K, Ogawa H, Gomi T, Fujioka M, Takusagawa F; ''Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase.''; J Mol Biol, 2002 PubMed Europe PMC Scholia
  7. Shirai H, Blundell TL, Mizuguchi K; ''A novel superfamily of enzymes that catalyze the modification of guanidino groups.''; Trends Biochem Sci, 2001 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
128231view13:39, 29 January 2024EweitzSoften disease color
128183view22:59, 28 January 2024EweitzFix label rendering issue in site by not PathVisio; refine alignments
122630view10:54, 22 April 2022FehrhartUpdated pathway node layout
122555view02:13, 16 April 2022EweitzModified title
122509view12:31, 13 April 2022DeSladded chapter nr
122508view12:29, 13 April 2022DeSlLayout updates
122343view12:23, 21 March 2022TimZottiAdd corrected line connection
122308view16:26, 17 March 2022DeSlOntology Term : 'cerebral creatine deficiency syndrome' added !
122307view16:23, 17 March 2022DeSlOntology Term : 'Fanconi syndrome pathway' added !
122306view16:23, 17 March 2022DeSlOntology Term : 'Fanconi renotubular syndrome 1' added !
122305view16:21, 17 March 2022DeSlOntology Term : 'optic atrophy' added !
122304view16:21, 17 March 2022DeSlOntology Term : 'gyrate atrophy' added !
122303view16:20, 17 March 2022DeSlOntology Term : 'gyrate atrophy pathway' added !
122302view16:20, 17 March 2022DeSlOntology Term : 'guanidinoacetate methyltransferase deficiency pathway' added !
122301view16:19, 17 March 2022DeSlAdded PW DataNodes
122300view16:15, 17 March 2022DeSlUpdated RHEA-ID structure
122299view16:13, 17 March 2022DeSlUpdated ID for CK to reviewed UniProt ID
122298view16:11, 17 March 2022DeSlOntology Term : 'DOID:0060174' removed !
122297view16:07, 17 March 2022DeSllast layout change
122296view16:06, 17 March 2022DeSlMore layout updates, unified one OMIM ID to correct URL
122295view15:48, 17 March 2022DeSllayout of DataNodes, added alternative name for GATM
122294view15:46, 17 March 2022DeSlUpdated reaction directionality GATM protein
122259view13:40, 16 March 2022TimZottiAdded diseases and omim links
122256view13:32, 16 March 2022TimZottiAdded right metabolites
122231view10:31, 16 March 2022TimZottiOntology Term : 'disease pathway' added !
122230view10:30, 16 March 2022TimZottiOntology Term : 'classic metabolic pathway' added !
122225view10:11, 16 March 2022TimZottiAdded the correct omim links
122188view11:49, 15 March 2022TimZottiAdded disease for OAT
122187view11:34, 15 March 2022TimZottiAdded OMIM links

Connected the not connected lines Added literature references Added a legend

Added the correct CK protein
122150view11:45, 14 March 2022TimZottiOntology Term : 'GABA aminotransferase deficiency' added !
122149view11:44, 14 March 2022TimZottiOntology Term : 'guanidinoacetate methyltransferase deficiency' added !
122148view11:43, 14 March 2022TimZottiOntology Term : 'creatine transporter deficiency' added !
122147view11:43, 14 March 2022TimZottiOntology Term : 'AGAT deficiency' added !
122146view11:42, 14 March 2022TimZottiOntology Term : 'creatine metabolic pathway' added !
121597view18:06, 21 February 2022Andrafix typo
121550view10:36, 21 February 2022TimZottiModified description
121549view10:35, 21 February 2022TimZottiModified description
121543view10:11, 21 February 2022TimZottiI added the correct Rhea identifiers to the conversions
121535view09:57, 21 February 2022TimZottiChanged CK to protein instead of metabollite Added bidirectional conversions
121346view07:48, 16 February 2022TimZottiNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2-oxoglutarateMetaboliteCHEBI:16810 (ChEBI)
ADPMetaboliteCHEBI:456216 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
ArginineMetaboliteCHEBI:32682 (ChEBI)
CKProteinEC 2.7.3.2 (Enzyme Nomenclature)
CreatineMetaboliteCHEBI:16919 (ChEBI)
GAMTGeneProductENSG00000130005 (Ensembl)
GATMGeneProductENSG00000171766 (Ensembl)
Glutamate-5 -semialdehydeMetaboliteQ2823261 (Wikidata)
GlycineMetaboliteHMDB00123 (HMDB)
GuanidinoacetateMetaboliteCHEBI:16344 (ChEBI)
OATGeneProductENSG00000065154 (Ensembl)
ORNITHINEMetaboliteCHEBI:45453 (ChEBI)
Phospho -guanidinoacetateMetaboliteCHEBI:16034 (ChEBI)
PhosphocreatineMetaboliteHMDB01511 (HMDB)
Pyrroline-5-carboxylateMetaboliteCHEBI:15893 (ChEBI)
S-AdenosylhomocysteineMetaboliteCHEBI:16680 (ChEBI)
S-adenosylmethionineMetaboliteCHEBI:15414 (ChEBI)
SLC6A8GeneProductENSG00000130821 (Ensembl)
Vitamin B6MetaboliteCHEBI:27306 (ChEBI)
creatinineMetaboliteCHEBI:16737 (ChEBI)
glutamateMetaboliteCHEBI:14321 (ChEBI)
prolineMetaboliteCHEBI:26271 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2-oxoglutarateGlutamate-5 -semialdehydemim-conversionRHEA: 25163 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
2-oxoglutaratemim-conversionRhea: 25163 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer.
CreatinePhosphocreatinemim-conversionRHEA: 17160 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
Glutamate-5 -semialdehydePyrroline-5-carboxylatemim-conversionRHEA:28237 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
GuanidinoacetateCreatinemim-conversionRHEA: 10657 (Rhea)
GuanidinoacetatePhospho -guanidinoacetateRhea: 14148 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer.
GuanidinoacetatePhospho -guanidinoacetatemim-conversionRHEA:14148 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer.
Guanidinoacetatemim-conversionRHEA:13201 (Rhea)
ORNITHINEmim-conversionRHEA: 13201 (Rhea)
PhosphocreatineCreatinemim-conversionRhea: 17160 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
Pyrroline-5-carboxylateGlutamate-5 -semialdehydemim-conversionRhea: 28237 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
Pyrroline-5-carboxylateprolinemim-conversionRHEA:14112 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
prolinePyrroline-5-carboxylatemim-conversionRhea:14112 (Rhea) This conversion is bidirectional. I added two lines to make it more clear for the computer
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