BACKGROUND: Because betaine (BET) supplementation may improve muscular strength and endurance, it seems plausible that BET will also influence CrossFit performance (CF). PURPOSE: The aim of this study was to evaluate the effects of three weeks of BET supplementation on body composition, CF performance, muscle power in the Wingate anaerobic test (WAnT), and the concentrations of selected hormones. The secondary aims were to analyze the effectiveness of two different BET doses (2.5 and 5.0 g/d) and their interaction with the methylenetetrahydrofolate reductase (MTHFR) genotype. METHODS: The study was designed in a double-blinded randomized cross-over fashion. Forty-three CF practitioners completed the entire study. CF performance was measured using the Fight Gone Bad (FGB) workout and muscle power was evaluated in a 30-second WAnT. Body composition was determined by air-displacement plethysmography. Blood was drawn to assess hormone concentrations. The C677T single nucleotide polymorphism (rs180113) in the MTHFR gene was analyzed. RESULTS: FGB total improved with BET by 8.7 ± 13.6% (p < 0.001), but no significant changes were observed with placebo (- 0.4 ± 10.0%, p = 0.128). No changes were also observed in WAnT and body composition. After BET supplementation testosterone concentration increased by 7.0 ± 15.4% with BET (p = 0.046) (no change with placebo: 1.5 ± 19.6%, p = 0.884) but had no effect on concentrations of insulin-like growth factor or cortisol. Finally, there were no significant interactions between MTHFR genotype and BET dose in any outcome. CONCLUSIONS: BET supplementation may improve CF performance and increase testosterone concentration. However, there was no evidence of a difference between dosages (2.5 and 5.0 g/d) and MTHFR genotypes. The trial was registered on clinicaltrials.gov (NCT03702205) on 10 October 2018.
- MeSH
- betain * farmakologie MeSH
- dvojitá slepá metoda MeSH
- klinické křížové studie MeSH
- lidé MeSH
- potravní doplňky MeSH
- testosteron * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
The betaine/γ-aminobutyric acid (GABA) transporter 1 (BGT1) is one of the four GABA transporters (GATs) involved in the termination of GABAergic neurotransmission. Although suggested to be implicated in seizure management, the exact functional importance of BGT1 in the brain is still elusive. This is partly owing to the lack of potent and selective pharmacological tool compounds that can be used to probe its function. We previously reported the identification of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA), a selective substrate for BGT1 over GAT1/GAT3, but also an agonist for GABAA receptors. With the aim of providing new functional insight into BGT1, we here present the synthesis and pharmacological characterization of the tritiated analogue, [3H]ATPCA. Using traditional uptake assays at recombinant transporters expressed in cell lines, [3H]ATPCA displayed a striking selectivity for BGT1 among the four GATs ( Km and Vmax values of 21 μM and 3.6 nmol ATPCA/(min × mg protein), respectively), but was also found to be a substrate for the creatine transporter (CreaT). In experiments with mouse cortical cell cultures, we observed a Na+-dependent [3H]ATPCA uptake in neurons, but not in astrocytes. The neuronal uptake could be inhibited by GABA, ATPCA, and a noncompetitive BGT1-selective inhibitor, indicating functional BGT1 in neurons. In conclusion, we report [3H]ATPCA as a novel radioactive substrate for both BGT1 and CreaT. The dual activity of the radioligand makes it most suitable for use in recombinant studies.
- MeSH
- betain farmakologie MeSH
- biologický transport účinky léků MeSH
- GABA farmakologie MeSH
- membránové transportní proteiny účinky léků MeSH
- myši MeSH
- neurony účinky léků MeSH
- proteiny přenášející GABA přes plazmatickou membránu účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- dimethylglycin,
- MeSH
- antioxidancia * MeSH
- betain farmakologie terapeutické užití MeSH
- fyziologický stres účinky léků MeSH
- inositol farmakologie terapeutické užití MeSH
- lidé MeSH
- potravní doplňky * MeSH
- psychický stres prevence a kontrola MeSH
- sarkosin analogy a deriváty farmakologie terapeutické užití MeSH
- vitamin B komplex farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
Misfolding and aggregation of mutant enzymes have been proposed to play role in the pathogenesis of homocystinuria due to cystathionine β-synthase (CBS) deficiency. Chemical chaperones have been recently shown to facilitate proper assembly of several CBS mutants. To asses the number of patients that may respond to chaperone therapy, we examined the effect of selected CBS ligands and osmolytes on assembly and activity of 27 CBS mutants that represent 70% of known CBS alleles. The mutant enzymes were expressed in a bacterial system, and their properties were assessed by native Western blotting and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) assay, respectively. We studied the chaperoning activity of δ-aminolevulinic acid (δ-ALA)-a heme precursor-and of three osmolytes betaine, 2-aminoethanesulfonic acid (taurine), and glycerol. Fourteen mutants responded by at least 30% increase in the amount of correctly assembled tetramers and enzymatic activity to the coexpressional presence of either 0.5 mM δ-ALA, 100 mM betaine, and/or 750 mM glycerol. Eight of these mutants (p.R266K, p.P49L, p.R125Q, p.K102N, p.R369C, p.V180A, p.P78R, p.S466L) were rescuable by all of these three substances. Four mutants showed increased formation of tetramers that was not accompanied by changes in activity. Topology of mutations appeared to determine the chaperone responsiveness, as 11 of 14 solvent-exposed mutations were substantially more responsive than three of 13 buried mutations. This study identified chaperone-responsive mutants that represent 56 of 713 known patient-derived CBS alleles and may serve as a basis for exploring pharmacological approaches aimed at correcting misfolding in homocystinuria.
- MeSH
- alely MeSH
- betain farmakologie terapeutické užití MeSH
- cystathionin-beta-synthasa chemie účinky léků genetika metabolismus MeSH
- Escherichia coli metabolismus MeSH
- glycerol farmakologie MeSH
- homocystinurie farmakoterapie genetika metabolismus MeSH
- jednonukleotidový polymorfismus fyziologie MeSH
- konformace proteinů účinky léků MeSH
- kyselina aminolevulová farmakologie terapeutické užití MeSH
- lidé MeSH
- ligandy MeSH
- molekulární chaperony farmakologie terapeutické užití MeSH
- multimerizace proteinu účinky léků MeSH
- mutantní proteiny chemie účinky léků metabolismus MeSH
- sbalování proteinů účinky léků MeSH
- taurin farmakologie terapeutické užití MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
