Creatine

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Creatine
Creatine.png
Skeletal formula of neutral form of creatine
Creatine zwitterion.png
Skeletal formula of one of the zwitterionic forms of creatine
Creatine zwitterion ball.png
Ball and stick model of one zwitterionic form of creatine
Names
Systematic IUPAC name
2-[Carbamimidoyl(methyl)amino]acetic acid
Other names
N-Carbamimidoyl-N-methylglycine; Methylguanidoacetic acid; N-amidinosarcosine
Identifiers
3D model (JSmol)
3DMet
907175
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.278 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-306-6
240513
KEGG
MeSH Creatine
PubChem CID
RTECS number
  • MB7706000
UNII
  • InChI=1S/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9) Yes check.svgY
    Key: CVSVTCORWBXHQV-UHFFFAOYSA-N Yes check.svgY
  • CN(CC(=O)O)C(=N)N
Properties
C4H9N3O2
Molar mass 131.135 g·mol−1
AppearanceWhite crystals
Odor Odourless
Melting point 255 °C (491 °F; 528 K)
13.3 g L−1 (at 18 °C)
log P −1.258
Acidity (pKa)3.429
Basicity (pKb)10.568
Isoelectric point 8.47
Thermochemistry
171.1 J K−1 mol−1 (at 23.2 °C)
Std molar
entropy (S⦵298)
189.5 J K−1 mol−1
−538.06–−536.30 kJ mol−1
−2.3239–−2.3223 MJ mol−1
Pharmacology
C01EB06 ( WHO )
Pharmacokinetics:
3 hours
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
P261, P305+P351+P338
Related compounds
Related alkanoic acids
Related compounds
 Dimethylacetamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Creatine ( /ˈkriːətiːn/ or /ˈkriːətɪn/ ) [1] is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various tautomers in solutions (among which are neutral form and various zwitterionic forms). Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate (ATP), primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer. [2]

History

Creatine was first identified in 1832 when Michel Eugène Chevreul isolated it from the basified water-extract of skeletal muscle. He later named the crystallized precipitate after the Greek word for meat, κρέας (kreas). In 1928, creatine was shown to exist in equilibrium with creatinine. [3] Studies in the 1920s showed that consumption of large amounts of creatine did not result in its excretion. This result pointed to the ability of the body to store creatine, which in turn suggested its use as a dietary supplement. [4]

In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found evidence that ingesting creatine can dramatically boost the creatine content of the muscle. [5] [6] In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered phosphocreatine (creatine phosphate), and determined that creatine is a key player in the metabolism of skeletal muscle. It is naturally formed in vertebrates. [7]

The discovery of phosphocreatine [8] [9] was reported in 1927. [10] [11] [9] In the 1960s, creatine kinase (CK) was shown to phosphorylate ADP using phosphocreatine (PCr) to generate ATP. It follows that ATP - not PCr - is directly consumed in muscle contraction. CK uses creatine to "buffer" the ATP/ADP ratio. [12]

While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, the gold medal winner at 100 meters, had used creatine before the Olympics (however, it should also be mentioned that Linford Christie was found guilty of doping later in his career.). [13] An article in Bodybuilding Monthly named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, The Times also noted that 100 meter hurdler Colin Jackson began taking creatine before the Olympics. [14] [15]

Phosphocreatine relays phosphate to ADP. Phosphocreatine.svg
Phosphocreatine relays phosphate to ADP.

At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called Experimental and Applied Sciences (EAS) introduced the compound to the sports nutrition market under the name Phosphagen. [16] Research performed thereafter demonstrated that the consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores. [17]

The cyclic derivative creatinine exists in equilibrium with its tautomer and with creatine. Creatinine-tautomerism-2D-skeletal.svg
The cyclic derivative creatinine exists in equilibrium with its tautomer and with creatine.

Metabolic role

Creatine is a naturally occurring non-protein compound and the primary constituent of phosphocreatine, which is used to regenerate ATP within the cell. 95% of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, testes, and other tissues. [18] [19] The typical creatine content of skeletal muscle (as both creatine and phosphocreatine) is 120 mmol per kilogram of dry muscle mass, but can reach up to 160 mmol/kg through supplementation. [20] Approximately 1–2% of intramuscular creatine is degraded per day and an individual would need about 1–3 grams of creatine per day to maintain average (unsupplemented) creatine storage. [20] [21] [22] An omnivorous diet provides roughly half of this value, with the remainder synthesized in the liver and kidneys. [18] [19] [23]

Creatine is not an essential nutrient. [24] It is an amino acid derivative, naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for S-Adenosyl methionine (a derivative of methionine) to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis, the enzyme arginine:glycine amidinotransferase (AGAT, EC:2.1.4.1) mediates the reaction of glycine and arginine to form guanidinoacetate. This product is then methylated by guanidinoacetate N-methyltransferase (GAMT, EC:2.1.1.2), using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain. A cyclic form of creatine, called creatinine, exists in equilibrium with its tautomer and with creatine.

CreatineSynthesis(en).png

Phosphocreatine system

Proposed creatine kinase/phosphocreatine (CK/PCr) energy shuttle. CRT = creatine transporter; ANT = adenine nucleotide translocator; ATP = adenine triphosphate; ADP = adenine diphosphate; OP = oxidative phosphorylation; mtCK = mitochondrial creatine kinase; G = glycolysis; CK-g = creatine kinase associated with glycolytic enzymes; CK-c = cytosolic creatine kinase; CK-a = creatine kinase associated with subcellular sites of ATP utilization; 1 - 4 sites of CK/ATP interaction. Creatine kinase and phosphocreatine energy shuttle.png
Proposed creatine kinase/phosphocreatine (CK/PCr) energy shuttle. CRT = creatine transporter; ANT = adenine nucleotide translocator; ATP = adenine triphosphate; ADP = adenine diphosphate; OP = oxidative phosphorylation; mtCK = mitochondrial creatine kinase; G = glycolysis; CK-g = creatine kinase associated with glycolytic enzymes; CK-c = cytosolic creatine kinase; CK-a = creatine kinase associated with subcellular sites of ATP utilization; 1 – 4 sites of CK/ATP interaction.

Creatine is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP in skeletal muscle is usually 2–5 mM, which would result in a muscle contraction of only a few seconds. [25] During times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction catalysed by the enzyme creatine kinase (CK). The phosphate group is attached to an NH center of the creatine. In skeletal muscle, PCr concentrations may reach 20–35 mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK. [25] A proposed representation has been illustrated by Krieder et al. [26] Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle's ability to resynthesize ATP from ADP to meet increased energy demands. [27] [28] [29]

Creatine supplementation appears to increase the number of myonuclei that satellite cells will 'donate' to damaged muscle fibers, which increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4. [30]

Genetic deficiencies

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects. [31] Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT . Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain. [32]

Vegetarians

Some studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians. [33] [34] [32] [19] This finding is due probably to an omnivorous diet being the primary source of creatine. [35] Research shows that supplementation is needed to raise the concentration of creatine in the muscles of lacto-ovo vegetarians and vegans up to non-vegetarian levels. [33]

Pharmacokinetics

Most of the research to-date on creatine has predominantly focused on the pharmacological properties of creatine, yet there is a lack of research into the pharmacokinetics of creatine. Studies have not established pharmacokinetic parameters for clinical usage of creatine such as volume of distribution, clearance, bioavailability, mean residence time, absorption rate, and half life. A clear pharmacokinetic profile would need to be established prior to optimal clinical dosing. [36]

Dosing

Loading phase

Muscle Total Creatine Stores.png

An approximation of 0.3 g/kg/day divided into 4 equal spaced intervals has been suggested since creatine needs may vary based on body weight. [26] [20] It has also been shown that taking a lower dose of 3 grams a day for 28 days can also increase total muscle creatine storage to the same amount as the rapid loading dose of 20 g/day for 6 days. [20] However, a 28-day loading phase does not allow for ergogenic benefits of creatine supplementation to be realized until fully saturated muscle storage.

This elevation in muscle creatine storage has been correlated with ergogenic benefits discussed in the research section. However, higher doses for longer periods of time are being studied to offset creatine synthesis deficiencies and mitigating diseases. [37] [38] [32]

Maintenance phase

After the 5–7 day loading phase, muscle creatine stores are fully saturated and supplementation only needs to cover the amount of creatine broken down per day. This maintenance dose was originally reported to be around 2–3 g/day (or 0.03 g/kg/day), [20] however, some studies have suggested 3–5 g/day maintenance dose to maintain saturated muscle creatine. [17] [22] [39] [40]

Absorption

This graph shows the mean plasma creatine concentration (measured in mmol/L) over an 8-hour period following ingestion of 4.4 grams of creatine in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr). Plasma creatine concentration over time.jpg
This graph shows the mean plasma creatine concentration (measured in μmol/L) over an 8-hour period following ingestion of 4.4 grams of creatine in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr).

Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12 mg/L. A single 5 gram (5000 mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120 mg/L at 1–2 hours post-ingestion. Creatine has a fairly short elimination half life, averaging just less than 3 hours, so to maintain an elevated plasma level it would be necessary to take small oral doses every 3–6 hours throughout the day.

Clearance

It has been shown that once supplementation of creatine stops, muscle creatine stores return to baseline in 4–6 weeks. [20] [42] [40]

Exercise and sport

Creatine supplements are marketed in ethyl ester, gluconate, monohydrate, and nitrate forms. [43]

Creatine supplementation for sporting performance enhancement is considered safe for short-term use but there is a lack of safety data for long term use, or for use in children and adolescents. [44]

A 2018 review article in the Journal of the International Society of Sports Nutrition said that creatine monohydrate might help with energy availability for high-intensity exercise. [45]

Creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work (periods of work and rest) by 5% to 15%. [46] [47] [48] Creatine has no significant effect on aerobic endurance, though it will increase power during short sessions of high-intensity aerobic exercise. [49] [ obsolete source ] [50] [ obsolete source ]

A survey of 21,000 college athletes showed that 14% of athletes take creatine supplements to try to improve performance. [51] Non-athletes report taking creatine supplements to improve appearance. [51]

Research

Cognitive performance

Creatine is sometimes reported to have a beneficial effect on brain function and cognitive processing, although the evidence is difficult to interpret systematically and the appropriate dosing is unknown. [52] [53] The greatest effect appears to be in individuals who are stressed (due, for instance, to sleep deprivation) or cognitively impaired. [52] [53]

A 2018 systematic review found that "generally, there was evidence that short term memory and intelligence/reasoning may be improved by creatine administration", whereas for other cognitive domains "the results were conflicting". [54] Another 2023 review initially found evidence of improved memory function. [55] However, it was later determined that faulty statistics lead to the statistical significance and after fixing the "double counting", the effect was only significant in older adults. [56]

A 2023 systematic review found no evidence that creatine improved cognitive performance. The researches criticized the methodology of previous reviews. [57]

Muscular disease

A meta-analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance. [58] Creatine treatment does not appear to improve muscle strength in people who have metabolic myopathies. [58] High doses of creatine lead to increased muscle pain and an impairment in activities of daily living when taken by people who have McArdle disease. [58]

According to a clinical study focusing on people with various muscular dystrophies, using a pure form of creatine monohydrate can be beneficial in rehabilitation after injuries and immobilization. [59]

Mitochondrial diseases

Parkinson's disease

Creatine's impact on mitochondrial function has led to research on its efficacy and safety for slowing Parkinson's disease. As of 2014, the evidence did not provide a reliable foundation for treatment decisions, due to risk of bias, small sample sizes, and the short duration of trials. [60]

Huntington's disease

Several primary studies [61] [62] [63] have been completed but no systematic review on Huntington's disease has been completed yet.

ALS

It is ineffective as a treatment for amyotrophic lateral sclerosis. [64]

Testosterone

A 2021 systemic review of studies found that "the current body of evidence does not indicate that creatine supplementation increases total testosterone, free testosterone, DHT or causes hair loss/baldness". [65]

Adverse effects

Side effects include: [66] [67]

One well-documented effect of creatine supplementation is weight gain within the first week of the supplement schedule, likely attributable to greater water retention due to the increased muscle creatine concentrations by means of osmosis. [68]

A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea. [69] [70]

Renal function

Long-term creatine supplementation has not been proven safe for kidney patients. [71]

A 2019 systematic review published by the National Kidney Foundation investigated whether creatine supplementation had adverse effects on renal function. [72] They identified 15 studies from 1997 to 2013 that looked at standard creatine loading and maintenance protocols of 4–20 g/day of creatine versus placebo. They utilized serum creatinine, creatinine clearance, and serum urea levels as a measure of renal damage. While in general creatine supplementation resulted in slightly elevated creatinine levels that remained within normal limits, supplementation did not induce renal damage (P value< 0.001). Special populations included in the 2019 Systematic review included type 2 diabetic patients [73] and post-menopausal women, [74] bodybuilders, [75] athletes, [76] and resistance trained populations. [77] [78] [79] The study also discussed 3 case studies where there were reports that creatine affected renal function. [80] [81] [82]

In a joint statement between the American College of Sports Medicine, Academy of Nutrition and Dietetics, and Dietitians in Canada on performance enhancing nutrition strategies, creatine was included in their list of ergogenic aids and they do not list renal function as a concern for use. [83]

The most recent position stand on creatine from the Journal of International Society of Sports Nutrition states that creatine is safe to take in healthy populations from infants to the elderly to performance athletes. They also state that long term (5 years) use of creatine has been considered safe. [26]

It is important to mention that kidneys themselves, for normal physiological function, need phosphocreatine and creatine and indeed kidneys express significant amounts of creatine kinases (BB-CK and u-mtCK isoenzymes). [84] At the same time, the first of two steps for endogenous creatine synthesis takes place in the kidneys themselves. Patients with kidney disease and those undergoing dialysis treatment generally show significantly lower levels of creatine in their organs, since the pathological kidneys are both hampered in creatine synthesis capability and are in back-resorption of creatine from the urine in the distal tubules. In addition, dialysis patients lose creatine due to wash out by the dialysis treatment itself and thus become chronically creatine depleted. This situation is exacerbated by the fact that dialysis patients generally consume less meat and fish, the alimentary sources of creatine. Therefore, to alleviate chronic creatine depletion in these patients and allow organs to replenish their stores of creatine, it was proposed in a 2017 article in Medical Hypotheses to supplement dialysis patients with extra creatine, preferably by intra-dialytic administration. Such a supplementation with creatine in dialysis patients is expected to significantly improve the health and quality of the patients by improving muscle strength, coordination of movement, brain function and to alleviate depression and chronic fatigue that are common in these patients. [85] [ unreliable medical source? ]

Safety

Contamination

A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant. The most prevalent of these contaminants was creatinine, a breakdown product of creatine also produced by the body. [86] Creatinine was present in higher concentrations than the European Food Safety Authority recommendations in 44% of the samples. About 15% of the samples had detectable levels of dihydro-1,3,5-triazine or a high dicyandiamide concentration. Heavy metals contamination was not found to be a concern, with only minor levels of mercury being detectable. Two studies reviewed in 2007 found no impurities. [87]

Interactions

A National Institutes of Health study suggests that caffeine interacts with creatine to increase the rate of progression of Parkinson's Disease. [88]

Food and cooking

When creatine is mixed with protein and sugar at high temperatures (above 148 °C), the resulting reaction produces carcinogenic heterocyclic amines (HCAs). [89] Such a reaction happens when grilling or pan-frying meat. [90] Creatine content (as a percentage of crude protein) can be used as an indicator of meat quality. [91]

Dietary considerations

Creatine-monohydrate is suitable for vegetarians and vegans, as the raw materials used for the production of the supplement have no animal origin. [92]

See also

Related Research Articles

<span class="mw-page-title-main">Creatinine</span> Breakdown product of creatine phosphate

Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body.

Phosphagens, also known as macroergic compounds, are high energy storage compounds, also known as high-energy phosphate compounds, chiefly found in muscular tissue in animals. They allow a high-energy phosphate pool to be maintained in a concentration range, which, if it all were adenosine triphosphate (ATP), would create problems due to the ATP-consuming reactions in these tissues. As muscle tissues can have sudden demands for much energy, these compounds can maintain a reserve of high-energy phosphates that can be used as needed, to provide the energy that could not be immediately supplied by glycolysis or oxidative phosphorylation. Phosphagens supply immediate but limited energy.

<span class="mw-page-title-main">Adenosine monophosphate deaminase deficiency type 1</span> Medical condition

Adenosine monophosphate deaminase deficiency type 1 or AMPD1, is a human metabolic disorder in which the body consistently lacks the enzyme AMP deaminase, in sufficient quantities. This may result in exercise intolerance, muscle pain and muscle cramping. The disease was formerly known as myoadenylate deaminase deficiency (MADD).

<span class="mw-page-title-main">Glycogen storage disease type V</span> Human disease caused by deficiency of a muscle enzyme

Glycogen storage disease type V, also known as McArdle's disease, is a metabolic disorder, one of the metabolic myopathies, more specifically a muscle glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as one in 100,000, roughly the same as glycogen storage disease type I.

<span class="mw-page-title-main">Rhabdomyolysis</span> Human disease (condition) in which damaged skeletal muscle breaks down rapidly

Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly, often due to high intensity exercise over a short period of time. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of the muscle breakdown products, such as the protein myoglobin, are harmful to the kidneys and can cause acute kidney injury.

<span class="mw-page-title-main">Carnitine</span> Amino acid active in mitochondria

Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for free energy production, and also participates in removing products of metabolism from cells. Given its key metabolic roles, carnitine is concentrated in tissues like skeletal and cardiac muscle that metabolize fatty acids as an energy source. Generally individuals, including strict vegetarians, synthesize enough L-carnitine in vivo.

<span class="mw-page-title-main">Phosphocreatine</span> Chemical compound

Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine triphosphate, the energy currency of the cell.

<span class="mw-page-title-main">Creatine kinase</span> Class of enzymes

Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP.

Bodybuilding supplements are dietary supplements commonly used by those involved in bodybuilding, weightlifting, mixed martial arts, and athletics for the purpose of facilitating an increase in lean body mass. Bodybuilding supplements may contain ingredients that are advertised to increase a person's muscle, body weight, athletic performance, and decrease a person's percent body fat for desired muscle definition. Among the most widely used are high protein drinks, pre-workout blends, branched-chain amino acids (BCAA), glutamine, arginine, essential fatty acids, creatine, HMB, whey protein, ZMA, and weight loss products. Supplements are sold either as single ingredient preparations or in the form of "stacks" – proprietary blends of various supplements marketed as offering synergistic advantages.

β-Hydroxy β-methylbutyric acid Chemical compound

β-Hydroxy β-methylbutyric acid (HMB), otherwise known as its conjugate base, β-hydroxyβ-methylbutyrate, is a naturally produced substance in humans that is used as a dietary supplement and as an ingredient in certain medical foods that are intended to promote wound healing and provide nutritional support for people with muscle wasting due to cancer or HIV/AIDS. In healthy adults, supplementation with HMB has been shown to increase exercise-induced gains in muscle size, muscle strength, and lean body mass, reduce skeletal muscle damage from exercise, improve aerobic exercise performance, and expedite recovery from exercise. Medical reviews and meta-analyses indicate that HMB supplementation also helps to preserve or increase lean body mass and muscle strength in individuals experiencing age-related muscle loss. HMB produces these effects in part by stimulating the production of proteins and inhibiting the breakdown of proteins in muscle tissue. No adverse effects from long-term use as a dietary supplement in adults have been found.

<span class="mw-page-title-main">Branched-chain amino acid</span> Amino acid with a branched carbon chain

A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid and alloisoleucine.

<span class="mw-page-title-main">Bioenergetic systems</span> Metabolic processes for energy production

Bioenergetic systems are metabolic processes that relate to the flow of energy in living organisms. Those processes convert energy into adenosine triphosphate (ATP), which is the form suitable for muscular activity. There are two main forms of synthesis of ATP: aerobic, which uses oxygen from the bloodstream, and anaerobic, which does not. Bioenergetics is the field of biology that studies bioenergetic systems.

<span class="mw-page-title-main">CKMT2</span> Protein and coding gene in humans

Creatine kinase S-type, mitochondrial is an enzyme that in humans is encoded by the CKMT2 gene.

<span class="mw-page-title-main">Glycocyamine</span> Chemical compound

Glycocyamine is a metabolite of glycine in which the amino group has been converted into a guanidine by guanylation. In vertebrate organism it is then transformed into creatine by methylation.

<span class="mw-page-title-main">Theo Wallimann</span>

Theo Wallimann is a Swiss biologist who was research group leader and Adjunct-Professor at the Institute of Cell Biology ETH Zurich and later at the Institute of Molecular Health Science https://mhs.biol.ethz.ch/about-us/emeriti-formermembers/wallimann.html at the ETH Zurich at the Biology Department https://biol.ethz.ch/en/, of the ETH Zurich, Switzerland.

Creatine kinase U-type, mitochondrial, also called ubiquitous mitochondrial creatine kinase (uMtCK), is in humans encoded by CKMT1A gene. CKMT1A catalyzes the reversible transfer of the γ-phosphate group of ATP to the guanidino group of Cr to yield ADP and PCr. The impairment of CKMT1A has been reported in ischaemia, cardiomyopathy, and neurodegenerative disorders. Overexpression of CKMT1A has been reported related with several tumors.

<span class="mw-page-title-main">CKM (gene)</span> Protein and coding gene in humans

Creatine kinase, muscle also known as MCK is a creatine kinase that in humans is encoded by the MCK gene.

<span class="mw-page-title-main">Purine nucleotide cycle</span>

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.

Exertional rhabdomyolysis (ER) is the breakdown of muscle from extreme physical exertion. It is one of many types of rhabdomyolysis that can occur, and because of this, the exact prevalence and incidence are unclear.

Pre-workout is a generic term for a range of bodybuilding supplement products used by athletes and weightlifters to enhance athletic performance. Supplements are taken to increase endurance, energy, and focus during a workout. Pre-workout supplements contain a variety of ingredients such as caffeine and creatine, differing by capsule or powder products. The first pre-workout product entered the market in 1982, and since then the category has grown in use. Some pre-workout products contain ingredients linked to adverse effects. Although these products are not regulated, the Food and Drug Administration (FDA) warns consumers to be cautious when consuming them.

References

  1. ↑ Stout JR, Antonio J, Kalman E, eds. (2008). Essentials of Creatine in Sports and Health. Humana. ISBN   978-1-59745-573-2.
  2. ↑ Barcelos RP, Stefanello ST, Mauriz JL, Gonzalez-Gallego J, Soares FA (2016). "Creatine and the Liver: Metabolism and Possible Interactions". Mini Reviews in Medicinal Chemistry. 16 (1): 12–8. doi:10.2174/1389557515666150722102613. PMID   26202197. The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis.
  3. ↑ Cannan RK, Shore A (1928). "The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine". The Biochemical Journal. 22 (4): 920–9. doi:10.1042/bj0220920. PMC   1252207 . PMID   16744118.
  4. ↑ Volek JS, Ballard KD, Forsythe CE (2008). "Overview of Creatine Metabolism". In Stout JR, Antonio J, Kalman E (eds.). Essentials of Creatine in Sports and Health. Humana. pp. 1–23. ISBN   978-1-59745-573-2.
  5. ↑ Folin O, Denis W (1912). "Protein metabolism from the standpoint of blood and tissue analysis". Journal of Biological Chemistry. 12 (1): 141–61. doi: 10.1016/S0021-9258(18)88723-3 . Archived from the original on 3 May 2018. Retrieved 8 May 2018.
  6. ↑ Antonio, Jose (8 February 2021). "Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?". Journal of the International Society of Sports Nutrition. 18 (1): 13. doi: 10.1186/s12970-021-00412-w . PMC   7871530 . PMID   33557850.
  7. ↑ Brosnan JT, da Silva RP, Brosnan ME (May 2011). "The metabolic burden of creatine synthesis". Amino Acids. 40 (5): 1325–31. doi:10.1007/s00726-011-0853-y. PMID   21387089. S2CID   8293857.
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