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Acta Crystallographica. Section D,... May 2015When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth and establishes a new steady state by accumulating the...
When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth and establishes a new steady state by accumulating the osmoprotectant metabolite betaine. Effective osmoregulation has also been implicated in the acquirement of a profound antibiotic resistance by MRSA. Betaine can be obtained from the bacterial habitat or produced intracellularly from choline via the toxic betaine aldehyde (BA) employing the choline dehydrogenase and betaine aldehyde dehydrogenase (BADH) enzymes. Here, it is shown that the putative betaine aldehyde dehydrogenase SACOL2628 from the early MRSA isolate COL (SaBADH) utilizes betaine aldehyde as the primary substrate and nicotinamide adenine dinucleotide (NAD(+)) as the cofactor. Surface plasmon resonance experiments revealed that the affinity of NAD(+), NADH and BA for SaBADH is affected by temperature, pH and buffer composition. Five crystal structures of the wild type and three structures of the Gly234Ser mutant of SaBADH in the apo and holo forms provide details of the molecular mechanisms of activity and substrate specificity/inhibition of this enzyme.
Topics: Betaine; Betaine-Aldehyde Dehydrogenase; Binding Sites; Crystallography, X-Ray; Kinetics; Models, Molecular; NAD; Protein Binding; Protein Conformation; Staphylococcus aureus; Substrate Specificity
PubMed: 25945581
DOI: 10.1107/S1399004715004228 -
Brain Research Bulletin Jan 2024Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an...
Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1β and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.
Topics: Mice; Animals; Microglia; Betaine; Astrocytes; Chronic Pain; Freund's Adjuvant; Inflammation
PubMed: 38145759
DOI: 10.1016/j.brainresbull.2023.110863 -
The American Journal of Clinical... Jul 2008
Topics: Age Factors; Betaine; Biological Availability; Diet; Ethnicity; Homocysteine; Humans; Inflammation
PubMed: 18614747
DOI: 10.1093/ajcn/88.1.247 -
PloS One 2012Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency...
BACKGROUND
Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients.
METHODS
Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days.
PRINCIPAL FINDINGS
The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002).
CONCLUSIONS
Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk.
Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Betaine; Chromatography, High Pressure Liquid; Cohort Studies; Female; Heart Failure; Homocysteine; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Myocardial Infarction; New Zealand; Risk Factors; Sarcosine
PubMed: 22649561
DOI: 10.1371/journal.pone.0037883 -
Journal of Cancer Research and Clinical... Mar 2024Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid...
PURPOSE
Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules.
METHODS
In this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal-Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers.
RESULTS
In comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1-144.5) ng/ml) than those without lymph node metastasis (131 (84.8-201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively.
CONCLUSION
Plasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.
Topics: Humans; Betaine; Choline; Carnitine; Thyroid Nodule; Lymphatic Metastasis; Biomarkers; Methylamines
PubMed: 38503944
DOI: 10.1007/s00432-024-05666-w -
Biophysical Journal Sep 2017A group of small molecules that stabilize proteins against high hydrostatic pressure has been classified as piezolytes, a subset of stabilizing cosolutes. This...
A group of small molecules that stabilize proteins against high hydrostatic pressure has been classified as piezolytes, a subset of stabilizing cosolutes. This distinction would imply that piezolytes counteract the effects of high hydrostatic pressure through effects on the volumetric properties of the protein. The purpose of this study was to determine if cosolutes proposed to be piezolytes have an effect on the volumetric properties of proteins through direct experimental measurements of volume changes upon unfolding of model proteins lysozyme and ribonuclease A, in solutions containing varying cosolute concentrations. Solutions containing the proposed piezolytes glutamate, sarcosine, and betaine were used, as well as solutions containing the denaturants guanidinium hydrochloride and urea. Changes in thermostability were monitored using differential scanning calorimetry whereas changes in volume were monitored using pressure perturbation calorimetry. Our findings indicate that increasing stabilizing cosolute concentration increases the stability and transition temperature of the protein, but does not change the temperature dependence of volume changes upon unfolding. The results suggest that the pressure stability of a protein in solution is not directly affected by the presence of these proposed piezolytes, and so they cannot be granted this distinction.
Topics: Betaine; Calorimetry; Glutamic Acid; Hydrostatic Pressure; Models, Theoretical; Muramidase; Protein Stability; Ribonuclease, Pancreatic; Sarcosine; Solutions; Temperature; Urea
PubMed: 28803626
DOI: 10.1016/j.bpj.2017.07.012 -
Archives of Razi Institute Nov 2021This study aimed to determine the anti-depressant effect of betaine (BT) in ovariectomized mice and its possible interaction with nitrergic and serotoninergic systems....
This study aimed to determine the anti-depressant effect of betaine (BT) in ovariectomized mice and its possible interaction with nitrergic and serotoninergic systems. In experiment 1, the mice were divided into control and sham groups, ovariectomy (OVX), OVX+BT (12.5mg/kg), OVX+BT (25 mg/kg), and OVX+BT (50mg/kg) groups. In experiment 2, the mice were assigned into control and sham, OVX, OVX+BT (50mg/kg), OVX+L-NAME (10 mg/kg), as well as OVX+injection of the BT and L-NAME. Experiments 3-5 were similar to experiment 2, except for L-Arginine (50 mg/kg), Fluoxetine (5 mg/kg), and Cyproheptadine (4 mg/kg) that were injected instead of the L-NAME. Subsequently, forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed in this study. Moreover, this study determined serum Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and total antioxidant status levels. According to the findings, OVX increased immobility time, compared to the control group (P<0.05). In addition, BT (50mg/kg) decreased depression-induced immobility time, compared to the OVX group (P<0.05). The co-injection of the BT+L-NAME decreased depression-induced immobility time in TST and FST, followed by an increase in the number of crossing in OFT(P<0.05).Moreover, the co-injection of the BT+L-Arginine significantly diminished the antidepressant activity of BT on immobility time and decreased positive effect of BT on the number of crossing (P<0.05). The co-injection of the BT+Fluoxetine significantly amplified the antidepressant activity of BT on immobility time and number of crossing (P<0.05). Furthermore, the co-injection of the BT+Cyproheptadine decreased antidepressant activity of BT on immobility time and number of crossing (P<0.05). The BT (25 and 50mg/kg) reduced the MDA; however, it elevated SOD and GPx levels in OVX mice (P<0.05). It seems that antidepressant activity of BT mediates via nitrergic and serotoninergic systems in OVX mice.
Topics: Animals; Antidepressive Agents; Betaine; Depression; Female; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide
PubMed: 35355756
DOI: 10.22092/ari.2020.352221.1553 -
Orphanet Journal of Rare Diseases Mar 2019The Registry of Adult and Paediatric Patients Treated with Cystadane® - Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization... (Observational Study)
Observational Study
BACKGROUND
The Registry of Adult and Paediatric Patients Treated with Cystadane® - Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization safety study that aimed to identify safety of betaine anhydrous (Cystadane®) in the treatment of patients with inborn errors of homocysteine metabolism (homocystinuria) in order to minimise the treatment associated risks and establish better knowledge on its clinical use. The registry included patients of all ages with homocystinuria who were treated with betaine anhydrous in conjunction with other therapies. Clinical data were collected retrospectively from 2007 to 2013, then prospectively up to February 2014. All adverse events (AEs) reported during the study were recorded. The clinical and biological status of patients was monitored at least once a year.
RESULTS
A total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric [≤18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were treated with betaine anhydrous for a mean duration of 7.4 ± 4.3 years. The median total daily dose of betaine anhydrous at the first and last study visits was 6 g/day for cystathionine β-synthase (CBS)-deficient vitamin B6 responders and 9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the median daily dose increased in CBS-deficient B6 non-responders (from 6 to 9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between the first and last visits. Treatment caused a mean overall reduction of 29% in plasma homocysteine levels in the study population. A total of 277 AEs were reported during the study, of which two non-serious AEs (bad taste and headache) and one serious AE (interstitial lung disease) were considered to be drug related. Overall, betaine anhydrous was well tolerated with no major safety concerns.
CONCLUSIONS
Data from the RoCH registry provided real-world evidence on the clinical safety and efficacy of betaine anhydrous in the management of homocystinuria in paediatric and adult patients.
Topics: Adolescent; Adult; Betaine; Child; Child, Preschool; Female; France; Homocysteine; Homocystinuria; Humans; Infant; Male; Registries; Retrospective Studies; Spain; Treatment Outcome; Young Adult
PubMed: 30871635
DOI: 10.1186/s13023-019-1036-2 -
Animal : An International Journal of... Jul 2012To determine possible mechanisms of action that might explain the nutrient partitioning effect of betaine and conjugated linoleic acid (CLA) in Iberian pigs and to... (Comparative Study)
Comparative Study Randomized Controlled Trial
To determine possible mechanisms of action that might explain the nutrient partitioning effect of betaine and conjugated linoleic acid (CLA) in Iberian pigs and to address potential adverse effects, twenty gilts were restrictively fed from 20 to 50 kg BW Control, 0.5% betaine, 1% CLA or 0.5% betaine + 1% CLA diets. Serum hormones and metabolites profile were determined at 30 kg BW and an oral glucose test was performed before slaughter. Pigs were slaughtered at 50 kg BW and livers were obtained for chemical and histological analysis. Decreased serum urea in pigs fed betaine and betaine + CLA diets (11%; P = 0.0001) indicated a more efficient N utilization. The increase in serum triacylglycerol (58% and 28%, respectively; P = 0.0098) indicated that CLA and betaine + CLA could have reduced adipose tissue triacylglycerol synthesis from preformed fatty acids. Serum glucose, low-density lipoprotein (LDL) cholesterol and non-esterified fatty acids were unaffected. CLA and betaine + CLA altered serum lipids profile, although liver of pigs fed CLA diet presented no histopathological changes and triglyceride content was not different from Control pigs. Compared with controls, serum growth hormone decreased (20% to 23%; P = 0.0209) for all treatments. Although serum insulin increased in CLA, and especially in betaine + CLA pigs (28% and 83%; P = 0.0001), indices of insulin resistance were unaffected. In conclusion, CLA, and especially betaine + CLA, induced changes in biochemical parameters and hormones that may partially explain a nutrient partitioning effect in young pigs. Nevertheless, they exhibited weak, although detrimental, effects on blood lipids. Moreover, although livers were chemically and histologically normal, pigs fed CLA diet challenged with a glucose load had higher serum glucose than controls.
Topics: Analysis of Variance; Animal Nutritional Physiological Phenomena; Animals; Betaine; Dietary Proteins; Hormones; Insulin; Insulin Resistance; Linoleic Acids, Conjugated; Lipid Metabolism; Lipids; Liver; Obesity; Spain; Sus scrofa; Triglycerides; Urea
PubMed: 23031465
DOI: 10.1017/S1751731111002308 -
PloS One 2011Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is...
BACKGROUND
Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these.
METHODOLOGY
Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment.
PRINCIPAL FINDINGS
Plasma betaine negatively correlated with triglyceride (Spearman's r(s) = -0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r(s) = -0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin.
CONCLUSION
Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk.
Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Betaine; Cohort Studies; Diabetes Complications; Dietary Supplements; Female; Humans; Hypolipidemic Agents; Lipids; Male; Middle Aged; Sarcosine
PubMed: 21747945
DOI: 10.1371/journal.pone.0021666