Creatine metabolism (Homo sapiens)

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Bibliography

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

External references

DataNodes

Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:456216 (ChEBI)
ATP	Metabolite	CHEBI:30616 (ChEBI)
AdoHcy	Metabolite	CHEBI:16680 (ChEBI)
AdoMet	Metabolite	CHEBI:15414 (ChEBI)
CK octamers	Complex	R-HSA-200373 (Reactome)
CKB	Protein	P12277 (Uniprot-TrEMBL)
CKB, CKM	Complex	R-HSA-200343 (Reactome)
CKM	Protein	P06732 (Uniprot-TrEMBL)
CKMT1A	Protein	P12532 (Uniprot-TrEMBL)
CKMT2	Protein	P17540 (Uniprot-TrEMBL)
CREAT	Metabolite	CHEBI:16737 (ChEBI)
CRET	Metabolite	CHEBI:16919 (ChEBI)
GAA	Metabolite	CHEBI:16344 (ChEBI)
GAMT	Protein	Q14353 (Uniprot-TrEMBL)
GATM	Protein	P50440 (Uniprot-TrEMBL)
GATM dimer	Complex	R-HSA-71268 (Reactome)
Gly	Metabolite	CHEBI:57305 (ChEBI)
H+	Metabolite	CHEBI:15378 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
L-Arg	Metabolite	CHEBI:32682 (ChEBI)
L-Orn	Metabolite	CHEBI:15729 (ChEBI)
Na+	Metabolite	CHEBI:29101 (ChEBI)
Pcr	Metabolite	CHEBI:17287 (ChEBI)
Pi	Metabolite	CHEBI:18367 (ChEBI)
SLC6A11	Protein	P48066 (Uniprot-TrEMBL)
SLC6A12	Protein	P48065 (Uniprot-TrEMBL)
SLC6A7	Protein	Q99884 (Uniprot-TrEMBL)
SLC6A8	Protein	P48029 (Uniprot-TrEMBL)
SLC6A8-like proteins	Complex	R-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

Source	Target	Type	Database reference	Comment
	ADP	Arrow	R-HSA-200318 (Reactome)
	ADP	Arrow	R-HSA-200326 (Reactome)
ATP			R-HSA-200318 (Reactome)
ATP			R-HSA-200326 (Reactome)
	AdoHcy	Arrow	R-HSA-71286 (Reactome)
AdoMet			R-HSA-71286 (Reactome)
CK octamers		mim-catalysis	R-HSA-200326 (Reactome)
CKB, CKM		mim-catalysis	R-HSA-200318 (Reactome)
	CREAT	Arrow	R-HSA-71287 (Reactome)
	CRET	Arrow	R-HSA-200396 (Reactome)
	CRET	Arrow	R-HSA-71286 (Reactome)
CRET			R-HSA-200318 (Reactome)
CRET			R-HSA-200326 (Reactome)
CRET			R-HSA-200396 (Reactome)
	GAA	Arrow	R-HSA-71275 (Reactome)
GAA			R-HSA-71286 (Reactome)
GAMT		mim-catalysis	R-HSA-71286 (Reactome)
GATM dimer		mim-catalysis	R-HSA-71275 (Reactome)
Gly			R-HSA-71275 (Reactome)
	H+	Arrow	R-HSA-71286 (Reactome)
H2O			R-HSA-71287 (Reactome)
L-Arg			R-HSA-71275 (Reactome)
	L-Orn	Arrow	R-HSA-71275 (Reactome)
	Na+	Arrow	R-HSA-200396 (Reactome)
Na+			R-HSA-200396 (Reactome)
	Pcr	Arrow	R-HSA-200318 (Reactome)
	Pcr	Arrow	R-HSA-200326 (Reactome)
Pcr			R-HSA-71287 (Reactome)
	Pi	Arrow	R-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 proteins		mim-catalysis	R-HSA-200396 (Reactome)