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Specificity of creatine in the control of muscle protein synthesis

Rockefeller University Press
Journal of Cell Biology (JCB)
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Abstract

This study provides additional evidence that creatine, an end product of contraction unique to muscle, is involved in the control of muscle protein synthesis. Creatine is shown to stimulate selectively the rate of synthesis of two major contractile proteins, actin and myosin heavy chain, in cultures of differentiating skeletal muscle. Creatine affects only the rate of synthesis and not the rate of degradation. Several creatine analogs are as effective as creatine in stimulating muscle protein synthesis, creatinine and amino acids such as arginine and glycine are not. Creatine stimulates myosin heavy chain synthesis twofold in cultures of embryonic muscle grown in either normal or dialyzed media.
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... 4) then suggested that the increased diameters may occur in response to an increased myofibular protein-synthesis rate. In support of this theory, Ingwall and colleagues (39)(40)(41)(42)(43) have determined that creatine plays a critical role in protein synthesis. These investigations suggest that creatine may be the chemical signal that links muscular activity and increased contractile protein synthesis during hypertrophy (39)(40)(41)(42)(43). Investigations examining the effects of creatine supplied in vitro have shown an increased synthesis rate of myosin heavy chains and actin when they are formed in vitro and in vivo. ...
... In support of this theory, Ingwall and colleagues (39)(40)(41)(42)(43) have determined that creatine plays a critical role in protein synthesis. These investigations suggest that creatine may be the chemical signal that links muscular activity and increased contractile protein synthesis during hypertrophy (39)(40)(41)(42)(43). Investigations examining the effects of creatine supplied in vitro have shown an increased synthesis rate of myosin heavy chains and actin when they are formed in vitro and in vivo. ...
... This finding may be the consequence of several factors related to GAA, Met, or both. First, creatine produced from GAA can stimulate synthesis of two major contractile proteins, actin and myosin [28]. Second, dietary GAA may spare arginine normally used as a creatine precursor [29], and arginine is the most abundant nitrogen carrier of tissue protein, and it promotes skeletal muscle protein synthesis. ...
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Objective: Tan lambs (n=36, 3 mo old, 19.1 ± 0.53 kg) were used to assess effects of dietary guanidinoacetic acid (GAA) and rumen-protected methionine (RPM) on growth performance, carcass traits, meat quality, and serum parameters. Methods: Lambs were randomly assigned to three treatment groups, with 6 pens per group and 2 lambs per pen. Dietary treatments were: basal diet alone (I); basal diet supplemented with 0.08% GAA + 0.06% RPM (II); and basal diet supplemented with 0.08% GAA + 0.08% RPM (III). Diets were provided three times a day for 90 d. Intake per pen was recorded daily and individual lamb body weight (BW) was measured monthly. Carcass traits were measured after slaughter and meat quality at the end of the experiment, blood samples were taken on a subgroup of lambs for analysis of indicators mostly related to protein metabolism. Results: Final BW and average daily gain for the first and second month, and for the entire experiment were greater in Treatment II compared to Treatment I (P < 0.05), whereas feed to gain ratio was lower (P < 0.05). Treatment II had the optimal dressing percentage and net meat weight proportion, as well as crude protein and intramuscular fat concentrations in muscles. Treatment II improved meat quality, as indicated by the greater water holding capacity, pH after 45 min and 48 h, and lower shear force and cooking loss. Dietary supplementation of GAA and RPM also increased the meat color a* and b* values at 24 h. Finally, Treatment II increased total protein, and serum concentrations of albumin and creatinine, but decreased serum urea nitrogen concentrations, indicating improved protein efficiency. Conclusion: In this study, 0.08% GAA + 0.06% RPM supplementation improved growth performance and meat quality of Tan lambs.
... The use of creatine and creatinine can be identified in the metabolomics profile of animals fed 1 and 2% of YME. Some studies have reported that creatinine is involved in muscle hypertrophy by increasing free fat mass (Ingwall et al., 1974;Pakise et al., 2001;Forbes et al., 2019). That idea corroborates with our companion article, in which animals fed 1 and 2% YME achieved a greater body weight and a lower carcass fat thickness (Lobo et al., 2020). ...
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This study aimed to evaluate the effect of dietary yerba mate (Ilex paraguariensis) extract (YME) on muscle metabolomics and physicochemical properties of lamb meat. Thirty-six uncastrated male lambs (90 d old) were fed experimental diets, which treatments consisted of 0%, 1%, 2%, and 4% inclusion of YME. Animals were fed for 50 d before slaughter. Muscle and meat samples were collected for metabolomics and meat quality analysis, respectively. The experiment was carried out in a randomized block design and analyzed using orthogonal contrasts. There was a quadratic effect of YME inclusion in tenderness (P < 0.05) and a positive linear effect on meat lightness (P < 0.05). No qualitative changes (P > 0.05) on individual metabolites were observed; however, changes in the quantitative metabolic proThis study aimed to evaluate the effect of dietary yerba mate (Ilex paraguariensis) extract (YME) on muscle metabolomics and physicochemical properties of lamb meat. Thirty-six uncastrated male lambs (90 d old) were fed experimental diets, which treatments consisted of 0%, 1%, 2%, and 4% inclusion of YME. Animals were fed for 50 d before slaughter. Muscle and meat samples were collected for metabolomics and meat quality analysis, respectively. The experiment was carried out in a randomized block design and analyzed using orthogonal contrasts. There was a quadratic effect of YME inclusion in tenderness (P < 0.05) and a positive linear effect on meat lightness (P < 0.05). No qualitative changes (P > 0.05) on individual metabolites were observed; however, changes in the quantitative metabolic profile were observed, showing that animals fed 1% and 2% of YME have a greater concentration of desirable endogenous muscle antioxidants, with direct impact on metabolic pathways related to beta-alanine metabolism and glutathione metabolism. Therefore, YME dietary supplementation up to 2% of the diet to lambs had little to no effects on the majority of meat quality traits evaluated; moreover, 4% of YME inclusion negatively affected feed intake and meat quality traits.file were observed, showing that animals fed 1% and 2% of YME have a greater concentration of desirable endogenous muscle antioxidants, with direct impact on metabolic pathways related to beta-alanine metabolism and glutathione metabolism. Therefore, YME dietary supplementation up to 2% of the diet to lambs had little to no effects on the majority of meat quality traits evaluated; moreover, 4% of YME inclusion negatively affected feed intake and meat quality traits.
... The use of creatine and creatinine can be identified in the metabolomics profile of animals fed 1% and 2% of YME. Some studies have reported that creatinine is involved in muscle hypertrophy by increasing free fat mass (Ingwall et al., 1974;Parise et al., 2001;Forbes et al., 2019). That idea corroborates with our companion article, in which animals fed 1% and 2% of YME achieved a greater body weight and a lower carcass fat thickness . ...
Article
This study aimed to evaluate the effect of dietary yerba mate (Ilex paraguariensis) extract (YME) on muscle metabolomics and physicochemical properties of lamb meat. Thirty-six uncastrated male lambs (90 days old) were fed experimental diets which treatments consisted of 0%, 1%, 2%, and 4% inclusion of YME. Animals were fed for 50 days before slaughter. Muscle and meat samples were collected for metabolomics and meat quality analysis, respectively. The experiment was carried out in a randomized block design and analyzed using orthogonal contrasts. There was a quadratic effect of YME inclusion in tenderness (P < 0.05) and a positive linear effect on meat lightness (P < 0.05). No qualitative changes (P > 0.05) on individual metabolites were observed; however, changes in the quantitative metabolic profile were observed, showing that animals fed 1 and 2% of YME have a greater concentration of desirable endogenous muscle antioxidants, with direct impact on metabolic pathways related to beta-alanine metabolism and glutathione metabolism. Therefore, YME dietary supplementation up to 2% of the diet to lambs had little to no effects on the majority of meat quality traits evaluated; moreover, 4% YME inclusion negatively affected feed intake and meat quality traits.
... При этом в мышце и крови значительно снижается рН и увеличивается содержание лактата, что может стимулировать секрецию анаболических гормонов [81,85,137]. Из-за деградации креатинфосфата в мышце происходит выраженное увеличение содержания креатина -одного из анаболических факторов [68,123,127,145]. В крови наблюдается увеличение содержания гормонов (гормон роста, тестостерон) и инсулиноподобного фактора роста-1 [8,12,77,79,110]. ...
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Физиологическое обеспечение тренировочного процесса высококвалифицированных спортсменов призвано выявить системы организма, ограничивающие и лимитирующие работоспособность спортсмена, подобрать физиологические тесты, корректно оценивающие влияние тренировочных нагрузок на функциональные показатели и на этой основе вносить своевременные изменения в тренировочный процесс. В настоящем руководстве предпринята попытка на основании обзора современных литературных данных и собственных исследований оценить роль различных физиологических факторов, влияющих на аэробную работоспособность высококвалифицированного лыжника и биатлониста, рассмотреть особенности тестирования некоторых функциональных показателей и их тренировки. На основании изучения динамики функциональных показателей высококвалифицированных спортсменов и данных современной литературы сформулированы предложения по стратегии подбора тренировочных нагрузок в макроцикле. Книга адресована тренерам, преподавателям и аспирантам институтов физической культуры, а также специалистам по физиологии, биохимии и спортивной медицине.
... The intramuscular uptake of Cr and the associated increase in intracellular water increases osmotic pressure, which in turn stimulates protein synthesis. Cellular hydration state is an important factor in controlling cellular protein turnover, i.e., an increase in cellular hydration inhibits proteolysis and stimulates protein synthesis [57] , whereas cell shrinkage has opposite effects [51,[58][59][60][61] . However, it is unclear whether acute Cr supplementation augments muscle protein by this mechanism [62,63] . ...
Chapter
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Creatine is a popular and widely used form of protein supplementation due to its efficacy in improving performance in healthy athletic populations via increased muscle mass and enhanced adenosine triphosphate (ATP) energy regeneration. If these effects of creatine supplementation were to be replicated in patients with rheumatoid arthritis (RA), then considerable clinical and patient benefit would ensue, as RA is a condition characterised by generalised muscle loss and substantially impaired physical function. The muscle loss inherent in RA is termed ‘rheumatoid cachexia,’ and its adverse consequences include reduced strength and physical function and, consequently, diminished quality of life. Whilst regular high-intensity exercise training has been shown to increase muscle mass and restore function in RA patients, this form of therapy has very low uptake amongst RA patients. Thus, acceptable alternatives are required. The aim of this review is to consider the potential efficacy of creatine as an anabolic and ergonomic therapy for RA patients. To date, only two studies have supplemented RA patients with creatine, and the findings from these investigations are inconsistent and inconclusive. However, trials in populations with similar losses of muscle mass and function as RA, including older adults and those with other muscle wasting conditions, indicate that creatine could be an efficacious way of improving muscle mass, strength and physical function in RA patients, and may offer an easy, safe and cheap means of treating rheumatoid cachexia and its consequences.
... In this section, we discuss the effects of creatine supplementation on the cellular level from studies of cell cultures, animals, and younger humans and how this might translate to the enhancement of muscle mass in older individuals. Ingwall et al 71,72 were the first to show that creatine added to muscle cell cultures could stimulate myosin heavy chain and actin protein synthesis, myofibrillar proteins important in the muscle contractile process. Important, however, is that these cells were from the breast muscles of chick embryos and, therefore, were muscle cells that were undergoing rapid differentiation (ie, development) and that they would most likely respond differently than human adult muscle cells. ...
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The loss of muscle mass and strength with aging results in significant functional impairment. Creatine supplementation has been used in combination with resistance training as a strategy for increasing lean tissue mass and muscle strength in older adults, but results across studies are equivocal. We conducted a systematic review and meta-analysis of randomized controlled trials of creatine supplementation during resistance training in older adults with lean tissue mass, chest press strength, and leg press strength as outcomes by searching PubMed and SPORTDiscus databases. Twenty-two studies were included in our meta-analysis with 721 participants (both men and women; with a mean age of 57–70 years across studies) randomized to creatine supplementation or placebo during resistance training 2–3 days/week for 7–52 weeks. Creatine supplementation resulted in greater increases in lean tissue mass (mean difference =1.37 kg [95% CI =0.97–1.76]; p<0.00001), chest press strength (standardized mean difference [SMD] =0.35 [0.16–0.53]; p=0.0002), and leg press strength (SMD =0.24 [0.05–0.43]; p=0.01). A number of mechanisms exist by which creatine may increase lean tissue mass and muscular strength. These are included in a narrative review in the discussion section of this article. In summary, creatine supplementation increases lean tissue mass and upper and lower body muscular strength during resistance training of older adults, but potential mechanisms by which creatine exerts these positive effects have yet to be evaluated extensively.
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Chapter
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