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Identification
NameCreatine
Accession NumberDB00148  (NUTR00022)
Typesmall molecule
Groupsapproved, nutraceutical
Description

An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(alpha-Methylguanido)acetic acidNot AvailableNot Available
(N-methylcarbamimidamido)acetic acidNot AvailableNot Available
(α-methylguanido)acetic acidNot AvailableNot Available
alpha-Methylguanidino acetic acidNot AvailableNot Available
CreatinNot AvailableNot Available
KreatinNot AvailableNot Available
MethylglycocyamineNot AvailableNot Available
N-(aminoiminomethyl)-N-methylglycineNot AvailableNot Available
N-AmidinosarcosineNot AvailableNot Available
N-Methyl-N-guanylglycineNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number57-00-1
WeightAverage: 131.1332
Monoisotopic: 131.069476547
Chemical FormulaC4H9N3O2
InChI KeyInChIKey=CVSVTCORWBXHQV-UHFFFAOYSA-N
InChI
InChI=1S/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)
IUPAC Name
2-(1-methylcarbamimidamido)acetic acid
SMILES
CN(CC(O)=O)C(N)=N
Mass Specshow(8.81 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acids and Derivatives
Alternative parentsTertiary Amines; Guanidines; Polyamines; Enolates; Carboxylic Acids; Amidines
Substituentsguanidine; tertiary amine; enolate; carboxylic acid; polyamine; amidine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Pharmacology
IndicationFor nutritional supplementation, also for treating dietary shortage or imbalance
PharmacodynamicsCreatine is a essential, non-proteinaceous amino acid found in all animals and, in some plants. Creatine is synthesized in the kidney, liver and pancreas from L-arginine, glycine and L-methionine. Following its biosynthesis, creatine is transported to the skeletal muscle, heart, brain and other tissues. Most of the creatine is metabolized in these tissues to phosphocreatine (creatine phosphate). Phosphocreatine is a major energy storage form in the body. Supplemental creatine may have an energy-generating action during anaerobic exercise and may also have neuroprotective and cardioprotective actions.
Mechanism of actionIn the muscles, a fraction of the total creatine binds to phosphate - forming creatine phosphate. The reaction is catalysed by creatine kinase, and the result is phosphocreatine (PCr). Phosphocreatine binds with adenosine diphosphate to convert it back to ATP (adenosine triphosphate), an important cellular energy source for short term ATP needs prior to oxidative phosphorylation.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life3 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)DiseaseSMP00362
L-arginine:glycine amidinotransferase deficiencyDiseaseSMP00507
Ornithine Aminotransferase Deficiency (OAT Deficiency)DiseaseSMP00363
Arginine and Proline MetabolismMetabolicSMP00020
Hyperornithinemia with gyrate atrophy (HOGA)DiseaseSMP00505
Creatine deficiency, guanidinoacetate methyltransferase deficiencyDiseaseSMP00504
Prolidase Deficiency (PD)DiseaseSMP00207
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)DiseaseSMP00188
Dimethylglycine Dehydrogenase DeficiencyDiseaseSMP00242
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)DiseaseSMP00179
DimethylglycinuriaDiseaseSMP00484
Glycine and Serine MetabolismMetabolicSMP00004
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]DiseaseSMP00506
Non Ketotic HyperglycinemiaDiseaseSMP00223
Hyperglycinemia, non-ketoticDiseaseSMP00485
Hyperprolinemia Type IIDiseaseSMP00360
Hyperprolinemia Type IDiseaseSMP00361
Prolinemia Type IIDiseaseSMP00208
SarcosinemiaDiseaseSMP00244
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9605
Blood Brain Barrier + 0.6849
Caco-2 permeable - 0.6228
P-glycoprotein substrate Non-substrate 0.5275
P-glycoprotein inhibitor I Non-inhibitor 0.9704
P-glycoprotein inhibitor II Non-inhibitor 0.8744
Renal organic cation transporter Non-inhibitor 0.8321
CYP450 2C9 substrate Non-substrate 0.7916
CYP450 2D6 substrate Non-substrate 0.767
CYP450 3A4 substrate Non-substrate 0.7585
CYP450 1A2 substrate Non-inhibitor 0.9136
CYP450 2C9 substrate Non-inhibitor 0.9068
CYP450 2D6 substrate Non-inhibitor 0.8954
CYP450 2C19 substrate Non-inhibitor 0.9157
CYP450 3A4 substrate Non-inhibitor 0.9346
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9969
Ames test Non AMES toxic 0.7522
Carcinogenicity Non-carcinogens 0.8138
Biodegradation Not ready biodegradable 0.7859
Rat acute toxicity 2.0088 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9653
hERG inhibition (predictor II) Non-inhibitor 0.9649
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Creatine monohydrate powder0.81USDg
Cytotine 1.5 g/15 ml liquid0.07USDml
Creatine powder0.01USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point255 dec °CPhysProp
water solubility1.33E+004 mg/L (at 18 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.2Not Available
Predicted Properties
PropertyValueSource
water solubility4.11e+00 g/lALOGPS
logP-1.6ALOGPS
logP-2.9ChemAxon
logS-1.5ALOGPS
pKa (strongest acidic)3.5ChemAxon
pKa (strongest basic)12.43ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area90.41ChemAxon
rotatable bond count2ChemAxon
refractivity42.01ChemAxon
polarizability12.17ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

Stefan Weiss, Helmut Krommer, “Process for the preparation of a creatine or creatine monohydrate.” U.S. Patent US5719319, issued September, 1963.

US5719319
General Reference
  1. Burke DG, Chilibeck PD, Parise G, Tarnopolsky MA, Candow DG: Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. Int J Sport Nutr Exerc Metab. 2003 Sep;13(3):294-302. Pubmed
  2. Dangott B, Schultz E, Mozdziak PE: Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med. 2000 Jan;21(1):13-6. Pubmed
  3. Hespel P, Op’t Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA: Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol. 2001 Oct 15;536(Pt 2):625-33. Pubmed
  4. Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL: Muscle creatine loading in men. J Appl Physiol. 1996 Jul;81(1):232-7. Pubmed
  5. Juhn M: Popular sports supplements and ergogenic aids. Sports Med. 2003;33(12):921-39. Pubmed
External Links
ResourceLink
KEGG CompoundC00300
PubChem Compound586
PubChem Substance46504868
ChemSpider566
ChEBI16919
ChEMBLCHEMBL283800
PharmGKBPA164778930
HETCRN
Drugs.comhttp://www.drugs.com/creatine.html
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/cre_0086.shtml
WikipediaCreatine
ATC CodesC01EB06
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(73.1 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Creatine kinase M-type

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Creatine kinase M-type P06732 Details

References:

  1. Zeng L, Hu Q, Wang X, Mansoor A, Lee J, Feygin J, Zhang G, Suntharalingam P, Boozer S, Mhashilkar A, Panetta CJ, Swingen C, Deans R, From AH, Bache RJ, Verfaillie CM, Zhang J: Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Circulation. 2007 Apr 10;115(14):1866-75. Epub 2007 Mar 26. Pubmed
  2. Zhou DQ, Hu Y, Liu G, Gong L, Xi Y, Wen L: Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme. Br J Sports Med. 2006 Dec;40(12):988-91. Epub 2006 Sep 25. Pubmed
  3. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. Pubmed

2. Creatine kinase U-type, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Creatine kinase U-type, mitochondrial P12532 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Slenzka K, Appel R, Kappel T, Rahmann H: Influence of altered gravity on brain cellular energy and plasma membrane metabolism of developing lower aquatic vertebrates. Adv Space Res. 1996;17(6-7):125-8. Pubmed
  4. Wyss M, Schlegel J, James P, Eppenberger HM, Wallimann T: Mitochondrial creatine kinase from chicken brain. Purification, biophysical characterization, and generation of heterodimeric and heterooctameric molecules with subunits of other creatine kinase isoenzymes. J Biol Chem. 1990 Sep 15;265(26):15900-8. Pubmed
  5. Muhlebach SM, Wirz T, Brandle U, Perriard JC: Evolution of the creative kinases. The chicken acidic type mitochondrial creatine kinase gene as the first nonmammalian gene. J Biol Chem. 1996 May 17;271(20):11920-9. Pubmed
  6. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. Pubmed

3. Creatine kinase B-type

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Creatine kinase B-type P12277 Details

References:

  1. Tian XF, Zhang XS, Li YH, Wang ZZ, Zhang F, Wang LM, Yao JH: Proteasome inhibition attenuates lung injury induced by intestinal ischemia reperfusion in rats. Life Sci. 2006 Oct 26;79(22):2069-76. Epub 2006 Jun 23. Pubmed
  2. Debrincat MA, Zhang JG, Willson TA, Silke J, Connolly LM, Simpson RJ, Alexander WS, Nicola NA, Kile BT, Hilton DJ: Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation. J Biol Chem. 2007 Feb 16;282(7):4728-37. Epub 2006 Dec 5. Pubmed
  3. Burklen TS, Hirschy A, Wallimann T: Brain-type creatine kinase BB-CK interacts with the Golgi Matrix Protein GM130 in early prophase. Mol Cell Biochem. 2007 Mar;297(1-2):53-64. Epub 2006 Oct 12. Pubmed
  4. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. Pubmed

4. Creatine kinase S-type, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Creatine kinase S-type, mitochondrial P17540 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Koufen P, Ruck A, Brdiczka D, Wendt S, Wallimann T, Stark G: Free radical-induced inactivation of creatine kinase: influence on the octameric and dimeric states of the mitochondrial enzyme (Mib-CK). Biochem J. 1999 Dec 1;344 Pt 2:413-7. Pubmed
  4. Wyss M, James P, Schlegel J, Wallimann T: Limited proteolysis of creatine kinase. Implications for three-dimensional structure and for conformational substrates. Biochemistry. 1993 Oct 12;32(40):10727-35. Pubmed
  5. Stachowiak O, Dolder M, Wallimann T, Richter C: Mitochondrial creatine kinase is a prime target of peroxynitrite-induced modification and inactivation. J Biol Chem. 1998 Jul 3;273(27):16694-9. Pubmed
  6. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40. Pubmed

5. Sodium- and chloride-dependent creatine transporter 1

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Sodium- and chloride-dependent creatine transporter 1 P48029 Details

References:

  1. Rosenberg EH, Munoz CM, Degrauw TJ, Jakobs C, Salomons GS: Overexpression of wild-type creatine transporter (SLC6A8) restores creatine uptake in primary SLC6A8-deficient fibroblasts. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):345-6. Pubmed
  2. Derave W, Straumann N, Olek RA, Hespel P: Electrolysis stimulates creatine transport and transporter cell surface expression in incubated mouse skeletal muscle: potential role of ROS. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1250-7. Epub 2006 Jul 18. Pubmed
  3. Lunardi G, Parodi A, Perasso L, Pohvozcheva AV, Scarrone S, Adriano E, Florio T, Gandolfo C, Cupello A, Burov SV, Balestrino M: The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds. Neuroscience. 2006 Nov 3;142(4):991-7. Epub 2006 Sep 1. Pubmed
  4. Campistol J, Arias-Dimas A, Poo P, Pineda M, Hoffman M, Vilaseca MA, Artuch R, Ribes A: [Cerebral creatine transporter deficiency: an infradiagnosed neurometabolic disease] Rev Neurol. 2007 Mar 16-31;44(6):343-7. Pubmed
  5. Wang L, Zhang Y, Shao M, Zhang H: Spatiotemporal expression of the creatine metabolism related genes agat, gamt and ct1 during zebrafish embryogenesis. Int J Dev Biol. 2007;51(3):247-53. Pubmed

6. Guanidinoacetate N-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: product of

Components

Name UniProt ID Details
Guanidinoacetate N-methyltransferase Q14353 Details

References:

  1. Almeida LS, Vilarinho L, Darmin PS, Rosenberg EH, Martinez-Munoz C, Jakobs C, Salomons GS: A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Mol Genet Metab. 2007 May;91(1):1-6. Epub 2007 Mar 1. Pubmed
  2. Kan HE, Meeuwissen E, van Asten JJ, Veltien A, Isbrandt D, Heerschap A: Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy. J Appl Physiol. 2007 Jun;102(6):2121-7. Epub 2007 Mar 8. Pubmed
  3. Wang L, Zhang Y, Shao M, Zhang H: Spatiotemporal expression of the creatine metabolism related genes agat, gamt and ct1 during zebrafish embryogenesis. Int J Dev Biol. 2007;51(3):247-53. Pubmed

1. Solute carrier family 22 member 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 5 O76082 Details

References:

  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 12:22