57-00-1 Usage
Uses
Used in Sports Nutrition:
Creatine is used as a nutritional supplement for promoting the adaptation of skeletal muscle to strenuous exercise and fighting against excessive fatigue for feeble individuals. It helps to increase muscle strength, power, and size, making it popular among athletes and fitness enthusiasts.
Used in Pharmaceutical Industry:
Creatine is used as a drug for the treatment of heart disease and respiratory insufficiency. It aids in improving exercise tolerance and overall cardiovascular health.
Used in Pharmaceutical Formulation:
Creatine is used for the preparation of a pharmaceutical formulation containing human growth hormone, which can help in muscle growth and development.
Used in Health Food Industry:
Creatine can be applied to compound health food with anti-aging and physical-power recovering effects. It helps to maintain muscle mass and strength, promoting overall health and well-being.
Used in Biochemical Research:
Creatine is used as a reagent for biochemical research, where it is involved in the rapid production of ATP associated with creatine kinases in skeletal muscle tissue. It acts as a nutraceutical and a neuroprotective agent, making it a valuable tool for studying various biological processes.
Used in Treatment of Neuromuscular Disorders:
Creatine is used for the treatment of conditions such as gyrate atrophy, McArdle's disease, muscular dystrophy, amyotrophic lateral sclerosis, and rheumatoid arthritis. It helps to improve muscle function and reduce symptoms associated with these disorders.
Physical and Chemical Properties
It is prismatic crystals (containing one crystal water molecule) with the melting point being 303 ℃ and the relative density of 1.33. It is soluble in boiling water and 98% acetic acid, slightly soluble in ethanol but insoluble in diethyl ether and butyrate. It can react with inorganic acid to obtain creatinine and co-heat with total soda lime to generate methylamine. It can be used to generate ammonia when being subject to azeotrope with potassium hydroxide and can react with potassium permanganate to generate methyl guanidine oxalic acid and guanidine; at room temperature, its aqueous solution can react with mercuric acetate role to generate guanidino glyoxylic acid, finally generating oxalic acid and guanidine In the reaction of the self-digestion in the muscle juice or organ extract, it can be converted to creatinine.
Production method
1. For taking lime nitrogen as raw materials for preparing creatine, there are three different process routes:
Lime nitrogen has direct reaction with the aqueous solution of sodium sarcosine to generate creatine.
Lime nitrogen is reacted with the methanol solution pre-saturated with dry hydrogen chloride gas to generate O-methylisourea hydrochloride which is further subject to reaction with sarcosine to generate creatine.
Upon the condition of passing air, lime nitrogen was reacted with aqueous hydrochloric acid to generate chlorinated formamidine chloride which further reacts with sarcosine sodium to generate creatine.
2. Cyanamide is reacted with chloroacetic acid, methylamine to generate creatine monohydrate.
3. Take thiourea and dimethyl sulfate as raw materials to generate S-methylisothiourea sulfate which then have reaction with sarcosine, sodium sarcosine or potassium sarcosine to generate creatine.
4. Take urea and dimethyl sulfate as raw materials to generate O-methyl isourea sulfate which then reacts with sodium sarcosine to generate creatine monohydrate.
Figure 1 The reaction formula for production of creatine
Operation method: add 3.3 mol of urea and 6 mL 50% H2SO4 to a 500 mL four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and a condenser; heat to 40 ℃, add drop wise of 3 mol dimethyl sulfate under stirring for 3 h; during the addition of raw materials, the temperature should be maintained at less than 70 ℃; after the completion of adding the material, stir for 2h about 70 ℃, and cool to obtain 561.8 g of O-methyl isourea sulfate. Add 61.7 of 36% aqueous solution of sodium sarcosinate to a 500 mL four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and a condenser, use 30% HCl to adjust the pH to about 11.0, and then add drop wise at 20 ℃ of 50 g of O-methyl isourea sulfate within 2 h; during the process of adding, drop wise, use 25% NaOH solution to adjust the pH and maintain the pH at about 11.0, after the addition was complete, stirring was continued at 40 ℃ for 2 h, and then cool the mixture at 0 ~5℃ for 2h and filter out the formed colorless crystals.
Use 2 × 15 mL of ice water to wash the filter cake to generate crude creatine monohydrate. Put the crude product into beaker, add water of 7 to 8 times the amount of crude product, heat to dissolve all the crude product, have liquid be subject to slow cooling at room temperature, crystallized, filter off the crystals, dry at a temperature below 50 ℃ to obtain the finished product of creatine monohydrate .
Pharmacological effects
1. Increase the water content of muscle cells:
During the initial stage of using creatine, you can feel obviously that the muscles can become larger and stronger. This is because creatine leads to that the body's muscle cells store a relatively large amount of water; and when all the muscle cells absorb large amounts of water and get increased volume, the muscle will certainly become more full, visible.
2. Help the muscle cells to store energy:
Human muscle fiber contains two different forms of creatine: non-bonded creatine and phosphate-containing creatine phosphate; among them, creatine phosphate accounts for about two-thirds of the total creatine content. When muscle gets contraction for exercise, the body will use a compound called ATP as the energy source. Unfortunately, the body's muscle cells can only support the ATP energy which is enough for only less than ten seconds rapid contraction. Therefore, more ATP must be produced in order to maintain continuous movement. At this time, the creatine phosphate stored in muscle will sacrifice their phosphoric acid group for biosynthesis of ATP again. Therefore, if the muscles contain more creatine, the muscle will have greater potential for exert its strength.
In addition, the supplement of the creatine can also help the exhausted muscles cells to rejuvenate. This is because when the muscle ATP energy is depleted, the body can use glycolysis pathway to produce lactic acid. When the body undergoes fierce exercise, a large number of lactic acid can be produced to make the muscles get soreness and fatigue; at this time if the muscle can store relative large amount of creatine phosphate for providing more ATP, the body will reduce the lactic acid manufacturing and reduce fatigue of muscle cells so that we can exercise more durable and more explosive.
3. Increase the biosynthesis of proteins:
The uptake of creatine makes the body be able to use more protein for muscle growth. Moreover, the two proteins in the muscle structure; actin and myosin, is exactly the main component to lead to muscle fiber contraction and movement. Therefore, if we can supplement sufficient amount of creatine for our bodies, our body can reduce the energy consumed for protein synthesis so that we can have more energy to synthesize large amount of actin and myosin cells, therefore, our muscle will certainly become stronger and more powerful.
Side Effects
1. Byproducts
Low-purity creatine not only has no apparent effect, but also is harmful to the human body. The major harmful substance is a derivatives called dicyandiamide. It will increase the burden of renal excretion. In the product of creatine of 99.99% purity, the dicyandiamide content is less than 20PPM.
2. Energy Source
The movement of the human muscles relies on the energy decomposed by adenosine triphosphate (ATP]. In high-intensity exercise, ATP will be totally depleted within a few seconds exploded, meaning it can only provide a few seconds of energy. In the aerobic exercise, it can be synthesized from the aerobic decomposition of carbohydrates and fats. But in anaerobic exercise, due to the lack of oxygen, creatine began to be involved to energy metabolism. It can combine with phosphoric acid to synthesize creatine phosphate (CP) and quickly replenish ATP. Theoretically, the more the creatine is stored, the more the synthesis of CP will be and the longer time the ATP can be supplied. In that case, the muscle can persist for a longer time at high-intensity exercise. In the recovering period, the synthesis of creatine still relies on carbohydrates for aerobic energy supplying. Therefore, the intake of carbohydrates should not be too small. Otherwise, after the decomposition of creatine, it can’t be synthesized and can’t supply the energy in the next training.
3. Danger
Because the creatine can quickly supplement energy, there may be overtraining phenomenon during the exercise.
Biochem/physiol Actions
Creatine is a nitrogenous compound that acts as a high-energy reservoir for the rapid regeneration of ATP. Approximately 95% of creatine is found in skeletal muscle, primarily as phosphocreatine. Creatine can be acquired through dietary consumption or formed from L-arginine, glycine, and L-methionine in a multi-step reaction that occurs in the kidneys and liver. Creatine is then transported to muscle tissue. Creatine supplementation is used for the enhancement of sports performance, primarily by increasing muscle mass. Creatine is also being investigated as a treatment of neuromuscular diseases, where it may aid in neuroprotection and by improving the cellular bioenergetic state.
Purification Methods
Likely impurities are creatinine and other guanidino compounds. It crystallises from the minimum volume of boiling H2O as the monohydrate. The hydrate is also obtained by dissolving in H2O and adding Me2CO. Drying under vacuum over P2O5 or drying at 100o gives the anhydrous base. The anhydrous base can be obtained also by dissolving the hydrate in H2O, seeding with the anhydrous base and cooling in ice. A m of 258 -268o(dec) was reported. The picrate crystallises from 17 parts of H2O with m of 218-220o(dec). [King J Chem Soc 2377 1930, Hoffmann et al. J Am Chem Soc 58 1730 1936, Mendel & Hodgkin Acta Cryst 7 443 1954, Greenstein & Winitz The Chemistry of the Amino Acids J. Wiley, Vol 3 p 2750 1961, Beilstein 4 III 1170, 4 IV 2425.]
Check Digit Verification of cas no
The CAS Registry Mumber 57-00-1 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 7 respectively; the second part has 2 digits, 0 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 57-00:
(4*5)+(3*7)+(2*0)+(1*0)=41
41 % 10 = 1
So 57-00-1 is a valid CAS Registry Number.
InChI:InChI=1/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)
57-00-1Relevant articles and documents
Versatile small molecule kinase assay through real-time, ratiometric fluorescence changes based on a pyrene-DPA-Zn2+complex
Kim, Jihoon,Oh, Jinyoung,Han, Min Su
, p. 10375 - 10380 (2021/03/23)
A real-time kinase assay method based on a ratiometric fluorescence probe that can be applied to various small-molecule kinases is described herein. The probe can trace the reversible interchange of ATP and ADP, which is a common phenomenon in most small-molecule kinase reactions, by a ratiometric fluorescence change. This property facilitates the monitoring of phosphorylation and dephosphorylation in small-molecule kinases, whereas most of the existing methods focus on one of these reactions. To prove the applicability of this method for small-molecule kinase assays, hexokinase and creatine kinase, which phosphorylate and dephosphorylate substrates, respectively, were analyzed. The ratiometric fluorescence change was correlated with the enzyme activity, and the inhibition efficiencies of the well-known inhibitors,N-benzoyl-d-glucosamine and iodoacetamide, were also monitored. Notably, the change in fluorescence can be observed with a simple light source by the naked eye.
Role of metal cations and oxyanions in the regulation of protein arginine phosphatase activity of YwlE from Bacillus subtilis
Huang, Biling,Huang, Chenyang,Huang, Shaohua,Liao, Xinli,Liu, Yan,Zhang, Yumeng,Zhao, Mingxiao,Zhao, Yufen,Zhao, Zhixing
, (2020/08/10)
Protein arginine phosphorylation (pArg) is a relatively novel posttranslational modification. Protein arginine phosphatase YwlE negatively regulates arginine phosphorylation and consequently induces the expression of stress-response genes that are crucial for bacterial stress tolerance and pathogenic homolog Staphylococcus aureus virulence. However, little is known about the factors that affect the enzymatic activity of YwlE with the exception of the effect of oxidative stress. Herein, based on the hydrolysis of the chromogenic substrate p-nitrophenyl phosphate (pNPP) by YwlE, we investigate the role of metal cations and oxyanions in the regulation of YwlE activity. Interestingly, among the various cations that we tested, Ca2+ activates YwlE, while other cations, including Ag+, Co2+, Cd2+, and Zn2+, are inhibitory. Furthermore, as chemical analogues of phosphate, oxyanions play multiple roles in phosphatase activity. The regulatory switch Cys within the catalytic site regulates YwlE activity. Specifically, the thiol of this Cys could be alkylated by IAM (iodoacetamide) or oxidized by H2O2, resulting in enzymatic inhibition. Conversely, reducing reagents, such as DTT (dithiothreitol), β-me (β-mercaptoethanol), and TCEP (tris(2-carboxyethyl)phosphine) enhance YwlE activity. Additionally, as a stable analogue to pArg, pAIE binds to YwlE with a Kd of 149.1 nM and a binding stoichiometry n of 1.2 and inhibits YwlE with an IC50 of 316.3 ± 12.73 μM. The inhibition and activation of YwlE may have broad implications for the physiology, pharmacology and toxicology of metal cations and oxyanions.
Synthetic method of creatine
-
Paragraph 0020, (2016/10/08)
The invention discloses a synthetic method of creatine. The method includes the steps of: adding water into a stainless steel reaction kettle having stirring, heating and reflux devices, adding guanidinoacetic acid and a catalyst AlCl3-K2CO3, adding dimethyl carbonate with stirring, heating the reaction kettle to increase the temperature therein, continuously performing the reaction, cooling the reaction product after the reaction is finished to separate creatine crystal out, and filtering and drying the creatine crystal to prepare the creatine. The synthetic method is less in reaction steps, is simple in process operation, is safe and environment-friendly and is greatly improved in product purity.
Stable aqueous compositions comprising amide-protected bioactive creatine species and uses thereof
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, (2011/11/01)
The present invention provides amide-protected creatine molecules and compositions, containing one or more bioactive forms of creatine in aqueous compositions, wherein bioactive forms of creatine do not appreciably degrade into creatinine. Also provided are various beneficial effects of administering aqueous compositions having at least one amide-protected creatine molecule.
Process for Preparing Creatine, Creatine Monohydrate or Guanidinoacetic Acid
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Page/Page column 3, (2009/07/10)
A process for producing creatine, creatine monohydrate or guanidinoacetic acid is proposed, wherein firstly N-methylethanolamine or ethanolamine is catalytically dehydrogenated in each case in alkaline solution and the sarcosinate or glycinate solutions that are obtained in this manner are finally reacted under acidic conditions with a guanylating agent such as for example O-alkylisourea or cyanamide. In this manner products are obtained in high yields and very good purity where in contrast to the prior art no traces whatsoever of hydrocyanic acid, formaldehyde, chloroacetic acid or ammonia are present. The formation of the toxicologically critical dihydrotriazine is also avoided.
Methods and compositions for diagnosing and treating arthritic disorders and regulating bone mass
-
Page/Page column 31, (2008/06/13)
The present invention relates to improved diagnostic methods for early detection of a risk for developing an arthritic disorder in humans, and screening assays for therapeutic agents useful in the treatment of arthritic disorders, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.
PROCESS FOR THE SYNTHESIS OF GUANIDINE DERIVATIVES
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Page 4, (2008/06/13)
The invention pertains to a process for the synthesis of guanidine derivatives of Formula (I) wherein X is selected from OH, OM wherein M is an alkali or earth alkali metal ion, and NR1R2 wherein R1 and R2 are independently H, C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, or C6-C10 aryl; which comprises a first step of reacting cyanogen chloride (N≡CCI) with NH3 in an organic solvent followed by a second step of reacting with an amine of Formula (II) wherein X has the previously given meaning, optionally followed by a step of converting a compound of Formula (I) into another compound of Formula (I).
Process for the preparation of creatine or creatine monohydrate
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Page column 2-3, (2008/06/13)
A process for the preparation of creatine or creatine monohydrate by reaction of sodium or potassium sarcosinate with cyanamide at a temperature from 20 to 150° C. and a pH from 7.0 to 14.0 comprises carrying out the pH adjustment with carbonic acid.
Preparation of substituted guanidine derivatives
-
, (2008/06/13)
Substituted guanidine derivatives of the formula I are prepared by reacting calcium cyanamide with a primary or secondary amino carboxylic acid or a primary or secondary amino sulfonic acid or their derivatives of the formula II where the substituents R1 and R2 have the meanings explained in the description.
Preparation of N-formamidinylamino acids from amino and formamidinesulfinic acids
Jursic,Neumann,McPherson
, p. 1656 - 1658 (2007/10/03)
A practical synthetic procedure for the conversion of amino acids into N-formamidinylamino acids using formamidinesulfinic acid in basic water solution is presented.
