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At least 19 recordsLinked to original sources

PubMed2025

Influence of creatine pyruvate on newly received cattle: insights from metagenomics and metabolomics.

Transport stress is a critical factor affecting the health and growth performance of beef cattle, potentially leading to oxidative stress, inflammation, and metabolic disorders. Creatine pyruvate (CrPyr), as a potential stress alleviator, has unclear mechanisms of action. We monitored the growth of 17 Simmental calves (control, n = 8; CrPyr, n = 9) over 30 days post-transportation, collecting rumen and blood samples on days 1/4, and 30. This study aims to investigate the effects of CrPyr on the growth performance, rumen microbiome, and metabolome of calves subjected to transport stress. Results showed that CrPyr increased average daily gain and antioxidant capacity, while reducing the level of stress hormones and inflammation. In the 4 days post-transport, CrPyr mainly increases Ruminococcus abundance to boost ruminal nitrogen metabolism, providing substrates for microbial protein synthesis. CrPyr also provides energy for the proliferation of Ruminococcus by regulating ATP synthesis genes (ATPVC) and enriching purine metabolism products. Meanwhile, it strengthens the host's amino acid metabolism, especially aspartate, to enhance antioxidative capacity. By day 30, CrPyr primarily boosts Prevotella abundance to regulate VFA synthesis, supplying host energy. It regulates the ATP synthesis gene ATPF0A and enriches purine metabolism products, supporting Prevotella growth. Increased citric acid and ATP levels further aid host growth. The findings distinctly demonstrate that the mechanisms by which CrPyr alleviates transport stress through the regulation of the rumen microbiome and metabolome, and confirms that its effects are time-dependent. These findings provide a theoretical basis for the development of stress-alleviation strategies based on CrPyr and hold significant implications for enhancing the health and production performance of beef cattle.

Animals↗

PubMed2026

Rumen microbiota-associated stress alleviation by creatine pyruvate in newly received cattle: a multi-omics study.

BACKGROUND: Stress experienced by newly received cattle is a significant challenge in the beef industry, frequently resulting in weakened immune responses and impaired growth. The rumen microbiota is essential to host health, and its imbalance can exacerbate stress. This study investigates the mechanisms by which creatine pyruvate (CrPyr) mitigates stress in newly received cattle through multi-omics approaches, including metagenomics, metabolomics, in vitro and in vivo experiments, and rumen microbiota transplantation (RMT) in mice. RESULTS: Our results revealed that CrPyr significantly reduces stress-related hormones (cortisol and adrenocorticotropic hormone) and inflammatory markers (IL-6, IL-1β, and TNF-α), and enhanced antioxidant capacity (SOD: 57.38 versus 46.93 U/mL, P < 0.05; GSH-Px: 305.87 versus 217.07 U/mL, P < 0.05; T-AOC: 9.62 versus 7.66 U/mL, P < 0.05). Metagenomic analysis demonstrated that CrPyr increased Prevotella abundance, a key rumen bacterium involved in volatile fatty acid (VFA) production, and enriches metabolic pathways associated with energy metabolism (ATP synthesis, and pyruvate metabolism) and antioxidant defense (glutathione metabolism, FC = 1.08, P < 0.05). In vitro and in vivo experiments, as well as RMT studies in mice, further validate these findings, demonstrating that CrPyr promote VFA synthesis and increased ATP production through the electron transport phosphorylation pathway. CONCLUSIONS: CrPyr modulates the abundance of ruminal Prevotella in transport-stressed cattle to enhance glutathione and VFA metabolism and to accelerate ATP and nucleotide synthesis, thereby alleviating stress in newly received cattle. This multimodal approach established CrPyr as an effective nutritional intervention that improves rumen function and increases livestock productivity. Video Abstract.

Animals↗

PubMed1980

[Preliminary results of a pilot study on the influence of pemoline on cerebral concentrations of lactate, pyruvate, creatine, creatinephosphate, ATP, AMP, and ADP (author's transl)].

Cerebral lactate, pyruvate, ATP, ADP, creatine and phosphocreatine concentrations were determined in old, 600 g, rats during daily application of 20 mg pemoline (Tradon) (n = 11) and placebo (n = 10). After application for 21 days there were observed no significant differences in ATP, ADP, AMP, creatine and phosphocreatine concentrations between pemoline and placebo treated rats. On the other hand, in pemoline-rats, there was a significant decrease in pyruvate, lactate concentrations and in lactate/pyruvate ratio. On account of an increased dopamine turnover caused by pemoline, a possible increasing aerobic glycolysis and thus a greater energy production are still being discussed.

Adenosine Diphosphate↗

PubMed1980

31P NMR quantitation of the displacement of equilibria of arginine, creatine, pyruvate, and 3-P-glycerate kinase reactions by substitution of sulfur for oxygen in the beta phosphate of ATP.

31P NMR measurements have been found to be a convenient means for simultaneously measuring the concentrations of several species in the equilibrium mixtures of the reactions catalyzed by arginine kinase and creatine kinase. MgATP + X in equilibrium MgADP + XP where X = arginine or creatine and XP = P-arginine or P-creatine. The free energy of phosphorylaton of various metabolites by adenosine 5'-O-(2-thiotriphosphate) at pH 8.0 and 30 degrees C is more exergonic than the corresponding phosphorylations by ATP by about 2.5 kcal/mol, resulting in a displacement of the equilibrium toward the nucleoside diphosphates by a factor of approximately 60. Since this factor does not depend on the nature of the metabolite, the equilibrium constants of thionucleotide reactions may be used to determined the equilibrium constants of corresponding oxynucleotide reactions which lie too far toward ATP. The equilibrium constants of the oxynucleotide reactions catalyzed by pyruvate kinase and 3-P-glycerate kinase calculated by this method from the experimentally determined equilibrium constants of the corresponding thionucleotide reactions are 3.1 x 10(-4) and 2.9 x 10(-4), respectively, under the experimental conditions used. The equilibrium constants and degree of stereoselectivity of the arginine kinase reaction are altered when Ca2+ replaces Mg2+ as the activating metal ion.

Adenosine Triphosphate↗

PubMed1983

Detection of carriers of X-linked gene for Duchenne muscular dystrophy by levels of creatine kinase and pyruvate kinase.

Creatine kinase (CK) is the enzyme most often utilized for the detection of carriers of the gene for X-linked muscular dystrophies. In 1974, pyruvate kinase (PK) levels were also found to be increased in these carriers. The objective of the present study, carried out on 77 women related to patients with Duchenne muscular dystrophy (DMD), was to compare the efficiency of the two enzymes in the detection process. Of the 11 obligate heterozygotes for the DMD gene in the group, 8 exhibited elevated mean CK levels, 6 had elevated mean PK levels, and 9 had elevated mean levels of at least one of the enzymes. Among the mothers of isolated patients, 2/13 had elevated mean CK levels, 3/13 had elevated mean PK levels, and 5/13 had elevated mean levels of at least one of these enzymes. Thus, the study confirms data obtained by other investigators indicating that the use of PK can increase the detection rate of carriers of the gene for X-linked muscular dystrophies.

Clinical Enzyme Tests↗

PubMed1999

Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players.

The purpose of this investigation was to study the efficacy of two dietary supplements on measures of body mass, body composition, and performance in 42 American football players. Group CM (n = 9) received creatine monohydrate, Group P (n = 11) received calcium pyruvate, Group COM (n = 11) received a combination of calcium pyruvate (60%) and creatine (40%), and Group PL received a placebo. Tests were performed before (T1) and after (T2) the 50 week supplementation period, during which the subjects continued their normal training schedules. Compared to P and PL, CM and COM showed significantly greater increases for body mass, lean body mass, 1 repetition maximum (RM) bench press, combined 1 RM squat and bench press, and static vertical jump (SVJ) power output. Peak rate of force development for SVJ was significantly greater for CM compared to P and PL. Creatine and the combination supplement enhanced training adaptations associated with body mass/composition, maximum strength, and SVJ; however, pyruvate supplementation alone was ineffective.

Adolescent↗

PubMed1987

Use of serum creatine kinase, pyruvate kinase, and genetic linkage for carrier detection in Duchenne and Becker dystrophy.

Carrier detection in Duchenne dystrophy (DD) and Becker dystrophy (BD) can be achieved with DNA probes that recognize restriction fragment length polymorphisms (RFLPs). In 22 families, we found that 16 of 23 females at risk for being DD or BD carriers could be provided with more definitive indications of carrier status beyond the use of creatine kinase/pyruvate kinase and pedigree analysis. RFLP analysis was not possible for six individuals despite potentially informative probes, because family members critical to the analysis were unavailable. In only one instance were all eight probes uninformative.

Creatine Kinase↗

PubMed1983

Effect of exercise on plasma pyruvate kinase and creatine kinase activity.

Plasma pyruvate kinase (PK) and creatine kinase (CK) were measured in healthy subjects engaging in (a) mild exercise, 30 min on an exercise cycle maintaining a pulse rate of 150/min, (b) moderate exercise, squeezing a ball until exhaustion with a sphygmomanometer cuff inflated above systolic pressure around the arm (max. 2 min) and (c) severe exercise, completing a marathon race. Mild exercise resulted in no change in enzyme levels over 24 h. Moderate exercise produced a small increase in PK but no change in CK. PK activity rose from 35.3 +/- 10 U/l pre-exercise to 41.3 +/- 13 U/l 15 min post-exercise (n = 8, p less than 0.025). Severe exercise (completing a marathon race) resulted in a 3-fold increase in PK from 26 (4-87) U/l pre-race to 69 (21-156) U/l immediately post-race, and also, as expected, an increase in CK from 60 (15-164) U/l to 257 (72-1535) U/l (results are means and ranges, n = 69, p less than 0.001 for both enzymes). Runners showed parallel increases in PK and CK (p less than 0.05 by Spearman rank correlation). The mean post-race activity of CK-MB was less than 5% of total CK but 18 runners had values greater than 6% (mean 4.8, range 1-18). We conclude that PK, like CK, is increased following exercise due to liberation of muscle enzyme. However, only severe exercise is likely to lead to a substantial increase in plasma PK activity and therefore prejudice its clinical usefulness as a diagnostic test.

Adolescent↗

PubMed1999

Differential coupling of smooth and skeletal muscle pyruvate kinase to creatine kinase.

The interaction of pyruvate kinase from skeletal (SKPK) and smooth (SMPK) muscle with MM-creatine kinase (MMCK) and BB-creatine kinase (BBCK) was assessed using temporal absorbance changes, variations in absorbance at different wavelengths, concentration dependence, association in an electric field, and PK kinetic activity. SKPK exhibits a time course of absorbance increase in the presence of MMCK with a time constant of 29.5 min. This increase occurs at all wavelength from 240 to 1000 nm. At 195 nm, the combination of SKPK and MMCK produces a decrease in absorption with electric fields of both 0 and 204 V/cm. The change in SKPK-MMCK is saturable. SKPK activity is significantly increased by the presence of MMCK in solutions of 0-32% ethanol. These results indicate specific SKPK-MMCK interaction. SMPK and BBCK did not exhibit similar coupling when the BBCK concentration dependence of absorbance or SMPK activity in solutions of 0-32% ethanol was determined. Both MMCK and BBCK increased SKPK activity; neither MMCK nor BBCK increased SMPK activity. The ability to form diazymatic complexes with creatine kinase appears to reside in SKPK. This coupling may account for the increased flux through PK without significant substrate changes seen during skeletal muscle activation. This coupling will not occur in smooth muscle.

Animals↗

PubMed1979

Turnover rates of hexokinase I, phosphofructokinase, pyruvate kinase and creatine kinase in slow-twitch soleus muscle and heart of the rabbit.

Hexokinase I was purified from rabbit heart to a specific activity of 70 U/mg protein. The purified enzyme was electrophoretically homogeneous with an apparent molecular weight of 102,000. Purified immunoglobulins from sheep were used to titrate the percentage of hexokinase I in various tissues of the rabbit. Precipitating antibodies from sheep were also prepared against rabbit muscle MM-creatine kinase, phosphofructokinase and pyruvate kinase. Apparent turnover rates of these phosphotransferases and of hexokinase I were determined in rabbit heart and soleus muscle by means of the immunoprecipitation technique after single pulse labelling with [U-14Cl]leucine in vivo. Apparent half-lives of phosphofructokinase, pyruvate kinase and hexokinase I were 0.56 d, 0.73 d and 0.93 d in rabbit heart. In slow-twitch soleus muscle half-lives of phosphofructokinase, pyruvate kinase, hexokinase II and creatine kinase were 0.63 d, 0.72 d, 0.85 d and 0.82 d. The similarity of the rate constants of degradation of these enzymes is interpreted as an indication that different tissue concentrations result primarily from different rates of synthesis.

Animals↗

PubMed1984

Plasma pyruvate kinase and creatine kinase activity in Becker muscular dystrophy.

Plasma creatine kinase (CK) and pyruvate kinase (PK) were measured in 31 obligate carriers of Becker muscular dystrophy (BMD), 36 BMD patients and appropriate controls. Mean plasma CK was 108 U/l in obligate carriers and 62 U/l in 43 age- and sex-matched controls (P less than 0.001 carriers vs controls). Control CK reference range was 31-125 U/l (mean +/- 2 SD of log transformed values). Mean plasma PK was 40 U/l in obligate carriers and 34 U/l in 56 controls (P less than 0.02 carriers vs controls). Control PK reference range was 18-61 U/l. Values of CK above the reference range upper limit were found in 13 of 31 BMD obligate carriers but only 2 showed elevated PK values. The sensitivity of CK in determining BMD carrier status, although only 42%, was markedly better than PK at 6.5%. Mean plasma CK in BMD patients was 2366 U/l, a 19-fold increase over the control value of 127 U/l (P less than 0.001 patients vs controls). Control CK reference range was 40-316 U/l. In contrast, mean plasma PK in BMD patients was 353 U/l, only 7-fold higher than the mean control value of 57 U/l (P less than 0.001 patients vs controls). Control PK reference range was 22-126 U/l. Clearly, the estimation of plasma PK as a means of determining BMD carrier status is markedly inferior to CK. Previous reports of increased sensitivity of PK compared with CK may have been due to artefactually elevated PK levels produced during sample preparation.

Adolescent↗

PubMed1985

Clinical investigation in Duchenne dystrophy: V. Use of creatine kinase and pyruvate kinase in carrier detection.

We have determined the value of creatine and pyruvate kinase (CK and PK) in carrier detection by evaluating 811 females in 73 families participating in the Collaborative Investigation of Duchenne Dystrophy. Thirty-nine obligate carriers, 244 normal controls (paternal females), as well as 76 possible carriers and 351 carrier suspects had three CK and PK specimens analyzed at a central laboratory. The CK and PK values varied with age in normals: both fell with age early in life, and CK rose after the fifth decade. Discriminant analysis indicated that the combination of mean CK and PK corrected for age yielded the best data for calculation of carrier probability. Using the best model, only 45% of obligate carriers could be identified at a false-positive rate of 2.5%. Daughters of obligate carriers have a disproportionate decline in CK and PK with age as compared to noncarrier females, suggesting that the rate of carrier detection will be higher in the first two decades. Our low rate of carrier detection, as compared to other studies, may reflect both the age of our obligate carrier population and the use of a control group that is more representative of the carrier population.

Adolescent↗

PubMed1976

Influence of severe potassium depletion and subsequent repletion with potassium on muscle electrolytes, metabolites and amino acids in man.

1. Two women with severe hypokalaemic alkalosis were investigated by means of muscle biopsy before and at the end of 2 and 3 weeks respectively of intense therapy with potassium chloride. 2. The muscle biopsy material was analysed for water, electrolytes, adenine nucleotides, phosphocreatine, free creatine, pyruvate, lactate, glycogen and free amino acids. The extra- and intra-cellular distribution of water, electrolytes and amino acids was calculated by the chloride method. 3. Both patients showed a marked loss of intracellular potassium and an increase in intracellular sodium concentration. The muscle magnesium content was also slightly decreased. After repletion with potassium chloride, muscle sodium and potassium became normal. 4. The contents of creatine phosphate, ATP, ADP, AMP, lactate and pyruvate were within normal limits, but the phosphocreatine/total creatine ratio was reduced. After repletion, a small change in the apparent creatine-phosphokinase equilibrium had occurred, suggesting a minor increase in intracellular pH. 5. The concentrations of the basic amino acids, lysine, arginine and ornithine were increased far above normal. The intracellular accumulation of arginine was much higher than the increase in lysine concentration and histidine concentration was normal. This differs from findings in potassium-depleted rats, where the intracellular lysine concentration is much higher than arginine concentration and histidine is high as well. After potassium repletion the intracellular concentration of ornithine, lysine and arginine became normal in one case and decreased considerable in the other. An increased intracellular concentration of glutamate and glutamine was also observed after potassium repletion.

Acidosis↗

PubMed1978

Serum creatine phosphokinase and pyruvate kinase in neuromuscular disorders and Duchenne dystrophy carriers.

Serum levels of creatine phosphokinase (CPK) and pyruvic kinase (PK) were determined in 42 controls, 57 patients with various neuromuscular disorders, and 23 female relatives of Duchenne dystrophy patients. CPK and PK enzyme activities were increased in comparable numbers of muscle disease patients and female carriers; there was no advantage in the combined use of the two tests. We did not confirm earlier reports suggesting that determination of PK is more valuable than CPK in carrier detection.

Adolescent↗

PubMed1998

Frequency-dependent fatigue development during electrical stimulation in the masseter muscle of pigtail monkeys.

Low-frequency fatigue was investigated in nine female and one male adult pigtail monkeys (Macaca nemestrina) with a mean weight of 5.3 kg (range 4.3 to 6.5 kg). After sedation and anesthesia, silver electrodes were inserted into the anterior and posterior parts of the right masseter muscle. The contralateral muscle was used as a control. The masseter muscles were stimulated for 3 minutes (4 Hz, 2 ms, 100 V). After a 5-minute rest period, the stimulation was repeated with the same duration and voltage but at a higher frequency of 8 Hz. Bite forces were measured, and muscle biopsies were obtained from the central part of the right masseter and immediately frozen in liquid nitrogen. After freeze-drying, a fluorometric analysis that used enzymatic methods for measuring levels of glycogen, glucose, lactate, pyruvate, creatine phosphate, nicotinamide-adenine dinucleotide (NAD), and reduced NAD (NADH) was performed. The bite force decreased by 12% after the initial 3 minutes of work. After the second contraction the bite force decreased to 56%. Prominent substrate depletion was observed. The precontraction levels of glycogen, glucose, and phosphocreatine were all reduced. The NADH and the NAD concentrations increased. An accumulation of metabolites was evident. The pyruvate increased by 32% and lactate levels increased by a factor of 3. The male measurements were comparable to the nine female measures for each assessment. The substantial substrate depletion in combination with a prominent accumulation of metabolites may contribute to the development of low-frequency fatigue.

Animals↗

PubMed2001

Neurotoxicity of glutamate uptake inhibition in vivo: correlation with succinate dehydrogenase activity and prevention by energy substrates.

Impairment of glutamate uptake or the reverse action of its transporters has been suggested as the mechanism responsible for the increased glutamate extracellular levels associated with ischemic neuronal damage. In previous studies we have shown that glutamate uptake inhibition by L-trans-pyrrolidine-2,4-dicarboxylate (PDC) in the rat striatum and hippocampus in vivo does not induce neuronal death despite the notable increase in the extracellular levels of glutamate and aspartate. However, PDC intracerebral administration leads to neuronal death in rats chronically injected with the mitochondrial toxin 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase (SDH). In the present study we have determined the time course of inhibition of SDH activity in the striatum of rats acutely injected with a single dose of 3-NP (20 mg/kg), and studied its relation to PDC neurotoxicity. PDC induced larger lesions when administered during maximum inhibition of SDH activity while smaller lesions were found when it was injected during recovery of enzyme activity. We also studied the neuroprotective effect of different energy substrates such as creatine, pyruvate, and the ketone bodies beta-hydroxybutyrate and acetoacetate in this experimental model. Our results show partial protection with all compounds except for beta-hydroxybutyrate that showed no protection, while MK-801 completely prevented PDC-induced neuronal damage. We believe that the present results might be of relevance for the understanding of the mechanisms responsible for ischemic neuronal death and its prevention.

3-Hydroxybutyric Acid↗

PubMed1994

Fatigue development during electrical stimulation in the masseter muscle of rhesus monkeys (Macaca mulatta).

Fatigue development was investigated in five adult female rhesus monkeys, 9-11 yr old (mean weight, 4.6 kg). After sedation and anaesthesia, silver electrodes were implanted in the anterior and posterior parts of the right masseter; the contralateral muscle was used as a control. The bite force was monitored. Muscle biopsies were obtained from the central part of the masseter and were immediately frozen in liquid nitrogen. After freeze-drying a fluorometric analysis using enzymatic methods for measuring levels of glycogen, glucose, lactate, pyruvate, creatine phosphate, creatine, NADH and NAD was made. The masseters were stimulated for 3 min (100 V, 4 Hz and 2 ms). After a 5-min rest period the stimulation was repeated with the same voltage, frequency and duration. The rhesus monkey masseters were easy to fatigue. After the stimulations 25% of the initial bite force remained. A marked substrate depletion was evident. The precontraction values of glycogen, glucose and phosphocreatine were reduced. The NADH concentration increased and the NAD content decreased. An accumulation of waste products was observed; the pyruvate increased by 92% and the lactate increased by a factor of 3. The substantial substrate depletion in combination with a prominent metabolic waste-product accumulation may induce a decrease in bite-force production.

Animals↗

PubMedDate not supplied

Serum creatine kinase and pyruvate kinase in Duchenne muscular dystrophy carrier detection.

The incidence of elevated serum creatine kinase (CK) and pyruvate kinase (PK) activities was compared in 20 definite carriers of Duchenne muscular dystrophy (DMD), 47 possible carriers, and 42 female controls. When adult age was not regarded as a variable, 70% of the definite carriers had elevated PK, 55% had elevated CK, and 75% had elevated PK or elevated CK or both, 38% of the possible carriers had elevated PK, 19% had elevated CK, and 40% had elevated PK or elevated CK or both. The detection efficiency of the CK test was influenced by the age of the subjects: the upper normal limit of serum CK in the adult controls was at the minimum between 21 and 35 years of age, and CK activity in some carriers declined from elevated to normal levels with increasing age. With these considerations, 70% of definite carriers had elevated CK and 80% had elevated PK and/or CK; 34% of the possible carriers had elevated CK and 43% had elevated PK and/or CK. On the basis of the PK and CK measurements, only 16 of 24 possible carrier mothers were likely to be DMD carriers, implying that the other 8 were non-carrier mothers of new mutant sons.

Adolescent↗