Creatine metabolism (Homo sapiens)

From WikiPathways

Jump to: navigation, search
26, 713, 810, 12, 135, 9, 11, 144mitochondrial matrixcytosolPiCKMT2 SLC6A12 CKMT1A GATM H+GATM dimerGlyCRETATPAdoMetGAACRETCKM L-OrnNa+GAMTCK octamersCRETAdoHcyH2ONa+SLC6A8-like proteinsL-ArgSLC6A8 GAASLC6A11 SLC6A7 CKB, CKMCKB ADPPcrCREAT413


Description

In humans, creatine is synthesized primarily in the liver and kidney, from glycine, arginine, and S-adenosylmethionine, in a sequence of two reactions. From the liver, creatine is exported to tissues such as skeletal muscle and brain, where it undergoes phosphorylation and serves as a short-term energy store. The mechanism by which creatine leaves producer tissues is unclear, but its uptake by consumer tissues is mediated by the SLC6A8 transporter.

Once formed, phosphocreatine undergoes a slow spontaneous reaction to form creatinine, which is excreted from the body. View original pathway at Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 71288
Reactome-version 
Reactome version: 75

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Wang PF, Flynn AJ, Naor MM, Jensen JH, Cui G, Merz KM, Kenyon GL, McLeish MJ.; ''Exploring the role of the active site cysteine in human muscle creatine kinase.''; PubMed Europe PMC Scholia
  2. Wyss M, Kaddurah-Daouk R.; ''Creatine and creatinine metabolism.''; PubMed Europe PMC Scholia
  3. Salomons GS, van Dooren SJ, Verhoeven NM, Marsden D, Schwartz C, Cecil KM, DeGrauw TJ, Jakobs C.; ''X-linked creatine transporter defect: an overview.''; PubMed Europe PMC Scholia
  4. Stöckler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K.; ''Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man.''; PubMed Europe PMC Scholia
  5. Haas RC, Korenfeld C, Zhang ZF, Perryman B, Roman D, Strauss AW.; ''Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase.''; PubMed Europe PMC Scholia
  6. BORSOOK H, DUBNOFF JW.; ''The hydrolysis of phosphocreatine and the origin of urinary creatinine.''; PubMed Europe PMC Scholia
  7. Iyengar MR, Coleman DW, Butler TM.; ''Phosphocreatinine, a high-energy phosphate in muscle, spontaneously forms phosphocreatine and creatinine under physiological conditions.''; PubMed Europe PMC Scholia
  8. Sora I, Richman J, Santoro G, Wei H, Wang Y, Vanderah T, Horvath R, Nguyen M, Waite S, Roeske WR.; ''The cloning and expression of a human creatine transporter.''; PubMed Europe PMC Scholia
  9. Khuchua ZA, Qin W, Boero J, Cheng J, Payne RM, Saks VA, Strauss AW.; ''Octamer formation and coupling of cardiac sarcomeric mitochondrial creatine kinase are mediated by charged N-terminal residues.''; PubMed Europe PMC Scholia
  10. Item CB, Stöckler-Ipsiroglu S, Stromberger C, Mühl A, Alessandrì MG, Bianchi MC, Tosetti M, Fornai F, Cioni G.; ''Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.''; PubMed Europe PMC Scholia
  11. Schlattner U, Gehring F, Vernoux N, Tokarska-Schlattner M, Neumann D, Marcillat O, Vial C, Wallimann T.; ''C-terminal lysines determine phospholipid interaction of sarcomeric mitochondrial creatine kinase.''; PubMed Europe PMC Scholia
  12. Humm A, Fritsche E, Mann K, Göhl M, Huber R.; ''Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue.''; PubMed Europe PMC Scholia
  13. Humm A, Fritsche E, Steinbacher S, Huber R.; ''Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.''; PubMed Europe PMC Scholia
  14. Haas RC, Strauss AW.; ''Separate nuclear genes encode sarcomere-specific and ubiquitous human mitochondrial creatine kinase isoenzymes.''; PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
114924view16:44, 25 January 2021ReactomeTeamReactome version 75
113369view11:44, 2 November 2020ReactomeTeamReactome version 74
112820view18:25, 9 October 2020DeSlOntology Term : 'creatine metabolic pathway' added !
112768view16:17, 9 October 2020ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:456216 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CK octamersComplexR-HSA-200373 (Reactome)
CKB ProteinP12277 (Uniprot-TrEMBL)
CKB, CKMComplexR-HSA-200343 (Reactome)
CKM ProteinP06732 (Uniprot-TrEMBL)
CKMT1A ProteinP12532 (Uniprot-TrEMBL)
CKMT2 ProteinP17540 (Uniprot-TrEMBL)
CREATMetaboliteCHEBI:16737 (ChEBI)
CRETMetaboliteCHEBI:16919 (ChEBI)
GAAMetaboliteCHEBI:16344 (ChEBI)
GAMTProteinQ14353 (Uniprot-TrEMBL)
GATM ProteinP50440 (Uniprot-TrEMBL)
GATM dimerComplexR-HSA-71268 (Reactome)
GlyMetaboliteCHEBI:57305 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
L-ArgMetaboliteCHEBI:32682 (ChEBI)
L-OrnMetaboliteCHEBI:15729 (ChEBI)
Na+MetaboliteCHEBI:29101 (ChEBI)
PcrMetaboliteCHEBI:17287 (ChEBI)
PiMetaboliteCHEBI:43474 (ChEBI)
SLC6A11 ProteinP48066 (Uniprot-TrEMBL)
SLC6A12 ProteinP48065 (Uniprot-TrEMBL)
SLC6A7 ProteinQ99884 (Uniprot-TrEMBL)
SLC6A8 ProteinP48029 (Uniprot-TrEMBL)
SLC6A8-like proteinsComplexR-HSA-3902491 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-200318 (Reactome)
ADPArrowR-HSA-200326 (Reactome)
ATPR-HSA-200318 (Reactome)
ATPR-HSA-200326 (Reactome)
AdoHcyArrowR-HSA-71286 (Reactome)
AdoMetR-HSA-71286 (Reactome)
CK octamersmim-catalysisR-HSA-200326 (Reactome)
CKB, CKMmim-catalysisR-HSA-200318 (Reactome)
CREATArrowR-HSA-71287 (Reactome)
CRETArrowR-HSA-200396 (Reactome)
CRETArrowR-HSA-71286 (Reactome)
CRETR-HSA-200318 (Reactome)
CRETR-HSA-200326 (Reactome)
CRETR-HSA-200396 (Reactome)
GAAArrowR-HSA-71275 (Reactome)
GAAR-HSA-71286 (Reactome)
GAMTmim-catalysisR-HSA-71286 (Reactome)
GATM dimermim-catalysisR-HSA-71275 (Reactome)
GlyR-HSA-71275 (Reactome)
H+ArrowR-HSA-71286 (Reactome)
H2OR-HSA-71287 (Reactome)
L-ArgR-HSA-71275 (Reactome)
L-OrnArrowR-HSA-71275 (Reactome)
Na+ArrowR-HSA-200396 (Reactome)
Na+R-HSA-200396 (Reactome)
PcrArrowR-HSA-200318 (Reactome)
PcrArrowR-HSA-200326 (Reactome)
PcrR-HSA-71287 (Reactome)
PiArrowR-HSA-71287 (Reactome)
R-HSA-200318 (Reactome) Cytosolic creatine kinase catalyzes the reaction of creatine and ATP to form phosphocreatine and ADP. The active form of the enzyme is a dimer. Monomers of the cytosolic enzyme occur in two isoforms, B and M, so called because of their abundance in brain and muscle respectively. The enzyme is widely expressed in the body and many tissues express both isoforms. Both homo- (BB, MM) and heterodimers (BM) are catalytically active.
R-HSA-200326 (Reactome) Creatine kinase octamers associated with the inner mitochondrial membrane catalyze the reaction of creatine and ATP to form phosphocreatine and ADP. Two mitochondrial creatine kinase proteins have been identified, one encoded by CKMT1A and B that is found in many tissues and one encoded by CKMT2 that is found in sarcomeres (Haas et al. 1988; Haas and Straus 1990). Studies of sarcomeric creatine kinase octamers suggest that their organization and association with phospholipids in the inner mitochondrial membrane may facilitate energy transfer from ATP generated in the mitochondrial matrix to cytosolic phosphocreatine (Khuchua et al. 1998; Schlattner et al. 2004).
R-HSA-200396 (Reactome) The SLC6A8 transport protein associated with the plasma membrane mediates the uptake of extracellular creatine and a sodium ion (Sora et al. 1994). Molecular and biochemical studies of patients deficient in SLC6A8 protein confirm this function in vivo (e.g., Salomons et al. 2003).
R-HSA-71275 (Reactome) Glycine amindinotransferase, localized to the mitochondrial intermembrane space, catalyzes the reaction of arginine and glycine to form guanidinoacetate and ornithine. The active form of the enzyme is a dimer (Humm et al. 1997 {EMBO J]; Humm et al 1997 [Biochem J]). Its function in vivo has been confirmed by molecular and biochemical studies of patients deficient in the enzyme (Item et al. 2001).
R-HSA-71286 (Reactome) Cytosolic guanidinoacetate methyltransferase catalyzes the reaction of S-adenosylmethionine and guanidinoacetate to form S-adenosylhomocysteine and creatine (Stockler et al. 1996).
R-HSA-71287 (Reactome) Cytosolic phosphocreatine spontaneously hydrolyzes to yield creatinine and orthophosphate (Borsook and Dubnoff 1947). Creatinine cannot be metabolized further and is excreted from the body in the urine. Creatinine formation proceeds at a nearly constant rate and the amount produced by an individual is a function of muscle mass, so urinary creatinine output is clinically useful as a normalization factor in assays of urinary output of other molecules. Iyengar et al. (1985) have suggested that an alternative reaction sequence, proceeding via phosphocreatinine but also spontaneous, may contribute to creatinine formation.
SLC6A8-like proteinsmim-catalysisR-HSA-200396 (Reactome)

Personal tools