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Due to their gastrointestinal immaturity or the severity of their pathology, many neonates require parenteral nutrition (PN). An amino acid (AA) solution is an important part of PN. Cysteine is a key AA for protein and taurine synthesis, as well as for glutathione synthesis, which is a cornerstone of antioxidant defenses. As cysteine could be synthesized from methionine, it is considered a nonessential AA. However, many studies suggest that cysteine is a conditionally essential AA in preterm infants due to limitations in their capacity for cysteine synthesis from methionine and the immaturity of their cellular cysteine uptake. This critical review discusses the endogenous synthesis of cysteine, its main biological functions and whether cysteine is a conditionally essential AA. The clinical evidence evaluating the effectiveness of the current methods of cysteine supplementation, between 1967 and 2023, is then reviewed. The current understanding of cysteine metabolism is applied to explain why these methods were not proven effective. To respond to the urgent need for changing the current methods of parenteral cysteine supplementation, glutathione addition to PN is presented as an innovative alternative with promising results in an animal model. At the end of this review, future directions for research in this field are proposed. [ABSTRACT FROM AUTHOR]

The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H2S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine β-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Measuring acyl lipid content and fatty acid composition is important in plant lipid research, and direct transmethylation followed by analysis with gas chromatography‐flame ionization detection has been broadly used in various studies. However, many existing protocols are time‐consuming and labor‐intensive, and the long reaction time under high temperature may artificially change fatty acid compositions of the samples. In this study, we optimized the direct transmethylation method for seed and leaf samples with a wide range of seed and tissue sizes, oil contents, and fatty acid profiles, which can be completed in 2 h. We also demonstrated that commercial disposable pipet tips, as well as polypropylene tubes under certain conditions, could be reliably used to replace glass tubes, Pasteur pipettes, and rubber bulbs to improve efficiency. Taken together, this optimized and generalized method could be used as a reliable and less time‐ and labor‐intensive approach to analyze acyl lipid content and fatty acid profile of plant samples. [ABSTRACT FROM AUTHOR]

In this article, we describe a proof of concept of the potential use of a biocatalytic process for the functionalization of technical soda lignins from wheat straw through the selective acylation of primary hydroxy groups of lignin oligomers by acetate or hexanoate, thus preserving their free, unreacted phenols. The selectivity and efficiency of the method, although they depend on the structural complexity of the starting material, have been proven on model compounds. Applied to technical lignins, the acylation yield is only moderate, due to structural and chemical features induced by the industrial mode of preparation of the lignins rather than to the lack of efficiency of the method. However, most of the physicochemical properties of the lignins, including their antioxidant potential, are preserved, advocating the potential use of these modified lignins for industrial applications.

Small-molecule carboxyl methyltransferases (CbMTs) constitute a small proportion of the reported methyltransferases, but they have received extensive attention due to their important physiological functions. Most of the small-molecule CbMTs isolated to date originate from plants and are members of the SABATH family. In this study, we identified a type of CbMT (OPCMT) from a group of Mycobacteria, which has a distinct catalytic mechanism from the SABATH methyltransferases. The enzyme contains a large hydrophobic substrate-binding pocket (~400 ų ) and utilizes two conserved residues, Thr20 and Try194, to retain the substrate in a favorable orientation for catalytic transmethylation. The OPCMT_like MTs have a broad substrate scope and can accept diverse carboxylic acids enabling efficient production of methyl esters. They are widely (more than 10,000) distributed in microorganisms, including several well-known pathogens, whereas no related genes are found in humans. In vivo experiments implied that the OPCMT_like MTs was indispensable for M. neoaurum, suggesting that these proteins have important physiological functions [ABSTRACT FROM AUTHOR]

BackgroundCurrently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with autism spectrum disorder (ASD). Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is ~18.7% (High Risk) whereas the risk of ASD in the general population is ~1.7% (Low Risk).MethodsIn this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism (ASD) or not (TD). Then these mothers were compared to a group of control mothers who have not had a child with autism before. A total of 107 mothers were in the High Risk category and 25 mothers in the Low Risk category. The High Risk category was further separated into 29 mothers in the ASD group and 78 mothers in the TD group.ResultsThe metabolic results indicated that among High Risk mothers, it was not possible to predict an autism pregnancy outcome. However, the metabolic profile was able to predict with approximately 90% sensitivity and specificity whether a mother fell into the High Risk group (18.7% risk) or Low Risk group (1.7% risk).ConclusionsBased upon these measurements it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3. However, differences in the folate-dependent transmethylation and transsulfuration metabolites are indicative of the risk level (High Risk of 18.7% vs. Low Risk of 1.7%) of the mother for having a child with ASD.

PBAT (poly(butylene adipate- co -terephthalate) is an important player in the field of bioplastics for its biodegradability performance and good mechanical properties. Awareness of the forecasted increased use of PBAT has prompted researchers to develop methods for its analysis in a variety of samples. Py-GC-MS, conventional or with derivatising agents, is a technique of excellence for the analysis of polymers that relies on a detailed structural knowledge of the evolved products. This study presents a comprehensive investigation on the chemical composition of the pyrolysate of PBAT evolved at 600 °C alone and in the presence of various reagents (hexamethyldisilazane, HMDS; acetic anhydride, Ac 2 O, tetramethylammonium hydroxide, TMAH). Identification of relevant pyrolysis products was confirmed through the analysis of pure standards and associated reagents/byproducts. A GC-MS data set of about 50 compounds was compiled, including open chain fragments of the polymer and their derivatives as well as single and mixed subunit cyclic dimers. A compound distinctive of PBAT (but-3-en-1-yl (4-((6-(but-3-en-1-yloxy)-6-oxohexanoyl)oxy)butyl) terephthalate) containing the adipic, terephthalic and butylene units was tentatively identified by its mass spectrum. Pyrolysis products with active hydrogens (alcoholic and carboxylic) were efficiently silylated by HMDS. Two pyrolysis products containing the hydroxybutyl moiety could be acetylated by pyrolysis with Ac 2 O. Thermally assisted hydrolysis and methylation with TMAH caused important transmethylation of the ester groups of the polymer chain with the formation of dimethyl adipate and dimethyl terephthalate. The importance of the results for the analysis of PBAT in commercial bioplastics and environmental samples was discussed. • GC-MS data of several pyrolysis products of PBAT. • Two pyrolysis products highly specific of PBAT were proposed. • Pyrolysis with HMDS successfully silylated pyrolysis products OH groups. • Derivatisation of hydroxybutyl terephathalate adipate by pyrolysis with acetic anhydride. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease is one of the most common chronic liver diseases with unclarified pathomechanism and without evidence-proven therapy. Dietary polyphenols, targeting oxidative stress, are at the center of investigations. Our aim was to examine the effects of a polyphenol rich extract on metal element homeostasis and transmethylation ability in non-alcoholic fatty liver model. A ten-day rat model was used (control group, hyperlipidemic group with fat-rich diet, hyperlipidemic group with fat-rich diet and polyphenol supplementation, N = 8 in each group). The hyperlipidemic diet increased the concentration of the majority of the elements with significantly higher contents of B, Co, Cu, Fe, Mg, Mn, Na, Ni, P, Se, Si, and Zn in the liver. Further elevation of Al, Pb, and Sn concentrations could be observed in polyphenol supplemented animals. The polyphenol supplement unexpectedly decreased the transmethylation ability of the liver (132.00 vs. 114.15 vs. 92.25 HCHO μg g−1) further. The results emphasize the possible role of altered metal and non-metal element concentrations and decreased transmethylation ability in the pathomechanism of fatty liver disease. Dietary supplementation with natural compounds may have undesirable effect as well, there is the necessity to improve the efficacy of polyphenol formulations because of their low oral bioavailability. [ABSTRACT FROM AUTHOR]

Background/Aim: Methionine addiction is a fundamental and general hallmark of cancer, termed the Hoffman effect. Methionine addiction is due to excessive use of and dependence on methionine by cancer cells. In the present report, we correlated the extent of methionine addiction and degree of malignancy with the amount and stability of methylated histone H3 lysine marks. Materials and Methods: We established low- and high-malignancy variants from a parental human pancreatic-cancer cell line and compared their sensitivity to methionine restriction and histone H3 lysine methylation status. Results: A low-malignancy, low-methionine-addiction revertant of the parental pancreatic-cancer cell line had less methylated H3K9me3 and was less sensitive to methionine restriction effected by recombinant methioninase (rMETase) than the parental cell line. A high-malignancy variant of the pancreatic cancer cell line had increased methylated H3K9me3 and was more sensitive to methionine restriction by rMETase with regard to inhibition of proliferation and to instability of histone H3 lysine methylation than the parental cell line. Orthotopic malignancy in nude mice was reduced in the low-methionine-addiction revertant and greater in the high-malignancy variant than in the parental cell line. Conclusion: The present study indicates that the degree of malignancy is linked to the extent of methionine addiction and the level and instability of trimethylation of histone H3, suggesting these phenomena are linked as a fundamental basis of oncogenic transformation. [ABSTRACT FROM AUTHOR]

Objective. S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are indicators of global transmethylation and may play an important role as markers of severity of COVID-19. Methods. The levels of plasma SAM and SAH were determined in patients admitted with COVID-19 (n = 56 , mean age = 61). Lung injury was identified by computed tomography (CT) in accordance with the CT0-4 classification. Results. SAM was found to be a potential marker of lung damage risk in COVID-19 patients (SAM > 80 nM ; CT3,4 vs. CT 0-2: relative ratio (RR) was 3.0; p = 0.0029). SAM / SAH > 6.0 was also found to be a marker of lung injury (CT2-4 vs. CT0,1: RR = 3.47 , p = 0.0004). There was a negative association between SAM and glutathione level (ρ = − 0.343 , p = 0.011). Interleukin-6 (IL-6) levels were associated with SAM (ρ = 0.44 , p = 0.01) and SAH (ρ = 0.534 , p = 0.001) levels. Conclusions. A high SAM level and high methylation index are associated with the risk of lung injury in patients with COVID-19. The association of SAM with IL-6 and glutathione indicates an important role of transmethylation in the development of cytokine imbalance and oxidative stress in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Elevated maternal homocysteine concentration has been described as a consequence of disruptions in methionine and/or folate metabolism which is associated with adverse outcomes and several obstetric complications inclusive of neural tube defects in offspring such as spina bifida, preeclampsia and spontaneous abortion. Aims and Objectives: The current study investigated the influence of maternal homocysteine metabolism in singleton pregnant women on the prevalence of Spina bifida in Osun State. Materials and Methods: Sixty (60) subjects attending Ladoke Akintola University of Technology Teaching Hospital and State Specialist Hospital in Osogbo, Osun State were randomly recruited for the study which spanned from January 2018 through April 2018 involving 30 apparently healthy singleton pregnant women classified according to gestational age and 30 apparently healthy age- and socio-economic status-matched non-pregnant women as controls. Haematocrit, haemoglobin concentration, total white cell count as well as the levels of homocysteine concentration were assessed. Results: Haematocrit and haemoglobin concentration in all three trimesters were significantly (p< 0.05) decreased when compared with their non-pregnant counterparts. There was however a significant (p< 0.05) increase in the expression of circulating homocysteine in all three trimesters compared to the control group, and an observed steady decline in the second trimester through the third trimester. Conclusion: These findings therefore imply that gestational perturbation of homocysteine metabolism may contribute to reduced risk of spina bifida in Osun State, Nigeria.

Developmental changes in hepatic methionine adenosyltransferase, cystathionine β‐synthase, cystathionase, and glycine N‐methyltransferase were determined in broiler chick embryos and hatched chicks by using radiometric and spectrometric methods. Hepatic free methionine, S‐adenosylmethionine, S‐adenosylhomocysteine, homocysteine, cystathionine, and cysteine levels were also investigated. Results showed an increase in hepatic MAT activity from E10 to E21 during embryogenesis, suggesting greater transmethylation rates throughout the rapid embryonic growth and development period. A strong positive correlation between embryo BW and MAT activity also supports this idea. The MAT specific activity continued to increase after hatching, but there was a negative correlation between chick BW and MAT activities from D1 to D49. This may indicate different MAT isozymes exist for chick embryo hepatic tissue compared to hepatic tissue of hatched chick and growing broilers. The developmental pattern of MAT isozymes could be critical for methionine metabolism to cope with the demand imposed on the embryo, chicks, and growing broilers. Additionally, the specific activity of hepatic CBS in chick embryos was determined to be lower compared to that observed in older broilers (35 and 49 days). Since liver CBS specific activity is at the lowest point from D1‐7 in young chicks, the ability to convert adequate homocysteine to cysteine through transsulphuration may be limiting for cysteine synthesis at this time. Steady‐state hepatic homocysteine levels in chick embryos and chicks may be a function of the rates of homocysteine formation, remethylation, and catabolism via the transsulphuration pathway. The present study indicates young chicks from D1 to D7 may have a limited ability for adequate transsulphuration; therefore, dietary cystine may be needed for optimum performance. [ABSTRACT FROM AUTHOR]

The excessive M1 polarization of macrophages drives the occurrence and development of inflammatory diseases. The reprogramming of macrophages from M1 to M2 can be achieved by targeting metabolic events. Taurine promotes for the balance of energy metabolism and the repair of inflammatory injury, preventing chronic diseases and complications. However, little is known about the mechanisms underlying the action of taurine modulating the macrophage polarization phenotype. In this study, we constructed a low-dose LPS/IFN-γ-induced M1 polarization model to simulate a low-grade pro-inflammatory process. Our results indicate that the taurine transporter TauT/SlC6A6 is upregulated at the transcriptional level during M1 macrophage polarization. The nutrient uptake signal on the membrane supports the high abundance of taurine in macrophages after taurine supplementation, which weakens the status of methionine metabolism, resulting in insufficient S-adenosylmethionine (SAM). The low availability of SAM is directly sensed by LCMT-1 and PME-1, hindering PP2Ac methylation. PP2Ac methylation was found to be necessary for M1 polarization, including the positive regulation of VDAC1 and PINK1. Furthermore, its activation was found to promote the elimination of mitochondria by macrophages via the mitophagy pathway for metabolic adaptation. Mechanistically, taurine inhibits SAM-dependent PP2Ac methylation to block PINK1-mediated mitophagy flux, thereby maintaining a high mitochondrial density, which ultimately hinders the conversion of energy metabolism to glycolysis required for M1. Our findings reveal a novel mechanism of taurine-coupled M1 macrophage energy metabolism, providing novel insights into the occurrence and prevention of low-grade inflammation, and propose that the sensing of taurine and SAM availability may allow communication to inflammatory response in macrophages. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cu-ReO x synergistic sites were implied to improve selective HDO performance. • The adsorption states of anisole and benzene were both adjusted through the interaction of Cu and ReO x. • The metal dispersion and electronic structure were improved by the interaction of Cu and ReO x. • Transmethylation process was promoted by acid sites on 2Cu-MoO x /SiO 2 and 2Cu-WO x /SiO 2. Selective hydrodeoxygenation (HDO) of lignin derived oxygenated aromatic compounds has great significance for lignin utilization and chemicals production. Hereby, bifunctional catalysts of Cu-MO x /SiO 2 (M = Re, Mo or W) were prepared to study the synergistic effect of Cu and MO x on the performance of anisole HDO. Characterizations indicated that Cu interacted strongly with the second metal species. As a result, more efficient sites exposed on catalysts surface, and metal dispersion and surface properties both were improved. Besides, adsorption strength for both oxygen atom and aromatic ring in reactant were all adjusted due to Cu-MO x interaction. Bimetallic catalyst Cu-ReO x /SiO 2 showed the highest HDO activity, while Cu-MoO x /SiO 2 and Cu-WO x /SiO 2 both preferred transmethylation because of their prominent acid properties. The Cu-ReO x composition was found to evidently affect the anisole conversion and selectivity of benzene, toluene and xylene (BTX). The highest BTX yield of 50.5 % could be achieved when Cu/Re ratio was 3. [ABSTRACT FROM AUTHOR]

Plant–virus interactions are greatly influenced by environmental factors such as temperatures. In virus‐infected plants, enhanced temperature is frequently associated with more severe symptoms and higher virus content. However, the mechanisms involved in such regulatory effects remain largely uncharacterized. To provide more insight into the mechanisms whereby temperature regulates plant–virus interactions, we analysed changes in the proteome of potato cv. Chicago plants infected with potato virus Y (PVY) at normal (22 °C) and elevated temperature (28 °C), which is known to significantly increase plant susceptibility to the virus. One of the most intriguing findings is that the main enzymes of the methionine cycle (MTC) were down‐regulated at the higher but not at normal temperatures. With good agreement, we found that higher temperature conditions triggered consistent and concerted changes in the level of MTC metabolites, suggesting that the enhanced susceptibility of potato plants to PVY at 28 °C may at least be partially orchestrated by the down‐regulation of MTC enzymes and concomitant cycle perturbation. In line with this, foliar treatment of these plants with methionine restored accumulation of MTC metabolites and subverted the susceptibility to PVY at elevated temperature. These data are discussed in the context of the major function of the MTC in transmethylation processes. [ABSTRACT FROM AUTHOR]

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Chemokine (C–C motif) ligand 2 (CCL2) has been associated with chronic metabolic diseases. We aimed to investigate whether Ccl2 gene overexpression is involved in the regulation of signaling pathways in metabolic organs. Biochemical and histological analyses were used to explore tissue damage in cisgenic mice that overexpressed the Ccl2 gene. Metabolites from energy and one-carbon metabolism in liver and muscle extracts were measured by targeted metabolomics. Western blot analysis was used to explore the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin pathways. Ccl2 overexpression resulted in steatosis, decreased AMPK activity and altered mitochondrial dynamics in the liver. These changes were associated with decreased oxidative phosphorylation and alterations in the citric acid cycle and transmethylation. In contrast, AMPK activity and its downstream mediators were increased in muscle, where we observed an increase in oxidative phosphorylation and increased concentrations of different metabolites associated with ATP synthesis. In conclusion, Ccl2 overexpression induces distinct metabolic alterations in the liver and muscle that affect mitochondrial dynamics and the regulation of energy sensors involved in cell homeostasis. These data suggest that CCL2 may be a therapeutic target in metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Elevated maternal homocysteine concentration has been described as a consequence of disruptions in methionine and/or folate metabolism which is associated with adverse outcomes and several obstetric complications inclusive of neural tube defects in offspring such as spina bifida, preeclampsia and spontaneous abortion. Aims and Objectives: The current study investigated the influence of maternal homocysteine metabolism in singleton pregnant women on the prevalence of Spina bifida in Osun State. Materials and Methods: Sixty (60) subjects attending Ladoke Akintola University of Technology Teaching Hospital and State Specialist Hospital in Osogbo, Osun State were randomly recruited for the study which spanned from January 2018 through April 2018 involving 30 apparently healthy singleton pregnant women classified according to gestational age and 30 apparently healthy age- and socio-economic status-matched non-pregnant women as controls. Haematocrit, haemoglobin concentration, total white cell count as well as the levels of homocysteine concentration were assessed. Results: Haematocrit and haemoglobin concentration in all three trimesters were significantly (p< 0.05) decreased when compared with their non-pregnant counterparts. There was however a significant (p< 0.05) increase in the expression of circulating homocysteine in all three trimesters compared to the control group, and an observed steady decline in the second trimester through the third trimester. Conclusion: These findings therefore imply that gestational perturbation of homocysteine metabolism may contribute to reduced risk of spina bifida in Osun State, Nigeria. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways.Methods and Findings: We first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD: n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]: n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations with severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD, p = 0.003; S-adenosyl methionine: higher in AD, p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD, p < 0.001; reduced glutathione [GSH]: higher in AD, p < 0.001); (3) polyamine synthesis/catabolism (spermidine: higher in AD, p = 0.004); (4) urea cycle (N-acetyl glutamate: lower in AD, p < 0.001); (5) glutamate-aspartate metabolism (N-acetyl aspartate: lower in AD, p = 0.002); and (6) neurotransmitter metabolism (gamma-amino-butyric acid: lower in AD, p < 0.001). Utilizing three Gene Expression Omnibus (GEO) datasets, we then examined mRNA expression levels of 71 genes encoding enzymes regulating key reactions within these pathways in the entorhinal cortex (ERC; AD: n = 25; CN: n = 52) and hippocampus (AD: n = 29; CN: n = 56). Complementing our metabolomics results, our transcriptomics analyses also revealed significant alterations in gene expression levels of key enzymatic regulators of biochemical reactions linked to transmethylation and polyamine metabolism. Our study has limitations: our metabolomics assays measured only a small proportion of all metabolites participating in the pathways we examined. Our study is also cross-sectional, limiting our ability to directly test how AD progression may impact changes in metabolite concentrations or differential-gene expression. Additionally, the relatively small number of brain tissue samples may have limited our power to detect alterations in all pathway-specific metabolites and their genetic regulators.Conclusions: In this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD. [ABSTRACT FROM AUTHOR]

Biodiesel can be prepared through the transmethylation of vegetable oils with short chained alcohols. The most common oils used as the starting material are edible oils, such as those extracted from palm or rapeseed. However, there is interest in producing biodiesel independently of food stock. Common castor is a non-edible oil crop that yields oil rich seeds with a high hydroxylated fatty acid content but that are not particularly appropriate for biodiesel formulation. The OLE1 castor mutant produces oils rich in oleic acid, with minor amounts of hydroxylated ricinoleic. Here, this trait was transferred to the IAS-RC-127 germplasm, which was cultivated as a perennial plant that yields seeds rich in oil, which could easily be extracted and transmethylated in a reaction with methanolic KOH. The resulting methyl esters comply with most of the requirements to be used as biodiesel, comparable to biofuels prepared from other high oleic oils. • Oil from high oleic castor seeds can be extracted and refined by regular methods. • High oleic castor oil can be transmethylated to produce biodiesel rich in oleate. • Biodiesel from high oleic castor displayed low viscosity values. • High oleic castor biodiesel fits better than regular castor biodiesel norm. • High oleic castor biodiesel displayed a low temperature melting range. [ABSTRACT FROM AUTHOR]

The distribution of steroids bearing short side-chains on the D-ring, with particular emphasis on the A-ring methylated series, is investigated over the late diagenesis-early catagenesis maturity range, by GC–MS analysis of a range of oils and selected immature source rock bitumens. A number of C 19 steranes are commonly observed in oils, including 5α,14β-androstane and a compound tentatively identified as 4α-methyl-5α,14β-androstane. C 21 and C 22 desmethyl steranes, along with minor amounts of C 23 –C 25 homologues, are ubiquitous, among which, by oil-window maturity, the 5α,14β,17β (diginane) isomers dominate, based on high m/z 218/217 ratios. The previously identified and commonly occurring C 21 and C 22 13β,17α-diapregnanes are accompanied by lesser amounts of their later-eluting 13α,17β isomers. 3-Methyl steranes appear limited to 5α,14β,17β isomers, primarily the C 22 and C 23 members, with no detectable corresponding diasteranes. Although relatively minor components overall, they are the main, if not only, methyl steranes in pre-Mesozoic samples. These distributions are consistent with the previously proposed mostly catagenetic generation from sterols bound to kerogen via their 3-hydroxy group with concomitant methylation at C-3 (in competition with reduction yielding desmethyl species). 4-Methyl steranes seem to be confined to post-Paleozoic samples, although trace amounts in older samples cannot be excluded. C 22 components dominate, comprising 4α-methyldiginane and a compound suggested to be 4β-methyl-13β,17α-diapregnane, the latter identification being supported by close covariance of its abundance with that of the corresponding desmethyl 13β,17α-diapregnane. A much smaller amount of what appears to be 4β-methyl-13α,17β-diapregnane is present; again, its relative abundance closely covaries with that of its desmethyl analogue. In addition, the relative abundances of these proposed 4-methyldiapregnanes correlate negatively with 4-methyl diasterene and positively with diapregnane contents in immature bitumen, further supporting the proposed identifications. The reason for the meagre amounts of C 23 4-methyl steranes is unclear, some possibilities are considered. Unlike their saturated counterparts, triaromatic pregnoids consistently exhibit methylation at C-2, C-3, C-4 and C-6, regardless of geological age, with C-3 and C-4 being most abundant, as also observed among C 27+ homologues. We suggest it reflects a degree of random, geochemical methylation/transmethylation of aromatic pregnoids, as recognized for methylphenanthrenes. It is most obvious in oils from pre-Mesozoic marine sources, but is concealed in oils from younger sources by abundant biological contributions of 4-methyl steroids, resulting in a broadly linear positive correlation of the 4-methyl/3-methyl ratios for saturated and triaromatic pregnoids. [ABSTRACT FROM AUTHOR]

Due to their gastrointestinal immaturity or the severity of their pathology, many neonates require parenteral nutrition (PN). An amino acid (AA) solution is an important part of PN. Cysteine is a key AA for protein and taurine synthesis, as well as for glutathione synthesis, which is a cornerstone of antioxidant defenses. As cysteine could be synthesized from methionine, it is considered a nonessential AA. However, many studies suggest that cysteine is a conditionally essential AA in preterm infants due to limitations in their capacity for cysteine synthesis from methionine and the immaturity of their cellular cysteine uptake. This critical review discusses the endogenous synthesis of cysteine, its main biological functions and whether cysteine is a conditionally essential AA. The clinical evidence evaluating the effectiveness of the current methods of cysteine supplementation, between 1967 and 2023, is then reviewed. The current understanding of cysteine metabolism is applied to explain why these methods were not proven effective. To respond to the urgent need for changing the current methods of parenteral cysteine supplementation, glutathione addition to PN is presented as an innovative alternative with promising results in an animal model. At the end of this review, future directions for research in this field are proposed.

• Adenosine is an endogenous anticonvulsant and seizure terminator. • Adenosine exerts potent anti-seizure effects through adenosine A1 receptor activation. • Adenosine has novel adenosine receptor independent effects as regulator of DNA methylation. • Adenosine has a novel role for disease modification and epilepsy prevention. • Therapeutic adenosine augmentation has potential to stop seizures and to prevent epilepsy. Adenosine is a well-characterized endogenous anticonvulsant and seizure terminator of the brain. Through a combination of adenosine receptor-dependent and -independent mechanisms, adenosine affects seizure generation (ictogenesis), as well as the development of epilepsy and its progression (epileptogenesis). Maladaptive changes in adenosine metabolism, in particular increased expression of the astroglial enzyme adenosine kinase (ADK), play a major role in epileptogenesis. Increased expression of ADK has dual roles in both reducing the inhibitory tone of adenosine in the brain, which consequently reduces the threshold for seizure generation, and also driving an increased flux of methyl-groups through the transmethylation pathway, thereby increasing global DNA methylation. Through these mechanisms, adenosine is uniquely positioned to link metabolism with epigenetic outcome. Therapeutic adenosine augmentation therefore not only holds promise for the suppression of seizures in epilepsy, but moreover the prevention of epilepsy and its progression overall. This review will focus on adenosine-related mechanisms implicated in ictogenesis and epileptogenesis and will discuss therapeutic opportunities and challenges. [ABSTRACT FROM AUTHOR]

The effect of polyphenolic bioactive substances, especially resveratrol (12.03 mg l−1), of an often consumed Hungarian red wine was investigated in a short term rat experiment. Male young Wistar albino rats were treated with high volumes of red wine (matching one bottle of wine/day for a 85 kg man) (N=5) and another alcoholic drink of the same alcohol concentration (N=5), corresponding to the circumstances of alcoholism, and 5 rats were in the control group. A total of 7 routine laboratory parameters were measured from the sera by kits. The changes of redox homeostasis (H-donor activity, induced chemiluminescence, diene-conjugates, GSHPx) were studied in blood plasma and/or in liver homogenates by spectrophotometric and luminometric methods. Transmethylation property of the liver was measured by overpressured layer chromatography (OPLC) technique. It was proven with in vitro OPLC analytical study that resveratrol reacted with methyl groups, and resveratrol was demonstrated to influence transmethylation processes as well as redox homeostasis. Red wine compounds do not protect from the harmful effects of alcohol, and even by high doses of resveratrol, the liver further deteriorates and the negative effect of alcohol increases. It has been confirmed that high doses of resveratrol do not provide protection against liver damage in those suffering from alcoholism. [ABSTRACT FROM AUTHOR]

Lipid derivatization technology-mediated fatty acid profiling studies have been suggested to dissect the contents of lipids in white fat and brown fat tissue. The focus of this study is to profile fatty acid lipidomics in brown adipose tissue and white adipose tissue of mice by derivatizing their lipids into fatty acid methyl esters via in situ transmethylation using a rice husk-derived biochar as porous media. The in situ transmethylation using biochar is advantageous in biological analysis because there was no loss of samples inevitably occurring in the loss of lipid in solvent extraction and purification steps. [ABSTRACT FROM AUTHOR]

Background: DL-2-hydroxy-4-methylthiobutyric acid (DL-HMTBA), an L-methionine (L-Met) hydroxyl analogue, has been suggested to be a dietary L-Met source. How dietary DL-HMTBA compared with L-Met affects whole-body L-Met kinetics in growing individuals is unknown.Objectives: We determined to what extent DL-HMTBA supplementation of an L-Met-deficient diet affects whole-body L-Met and L-cysteine (L-Cys) kinetics, protein synthesis (PS), and the L-Met incorporation rate in liver protein (L-MetInc) compared with L-Met and DL-Met supplementation in a piglet model.Methods: Forty-five, 28-d-old weaned piglets (male, German Landrace) were allocated to 4 dietary groups: L-Met-deficient diet [Control: 69% of recommended L-Met plus L-Cys supply; 0.22% standardized ileal digestible (SID) L-Met; 0.27% SID L-Cys; n = 12] and Control diet supplemented equimolarly to 100% of recommended intake with either L-Met (n = 12; LMET), DL-Met (n = 11; DLMET), or DL-HMTBA (n = 10; DLHMTBA). At 47 d of age, the piglets were infused with L-[1-13C; methyl-2H3]-Met and [3,3-2H2]-Cys to determine the kinetics and PS rates. Plasma amino acid (AA) concentrations, hepatic mRNA abundances of L-Met cycle and transsulfuration (TS) enzymes, and L-MetInc were measured.Results: During feed deprivation, L-Met kinetics did not differ between groups, and were ≤3 times higher in the fed state (P < 0.01). Remethylation (RM) was 31% and 45% higher in DLHMTBA than in DLMET and Control pigs, respectively, and the RM:transmethylation (TM) ratio was 50% higher in DLHMTBA than in LMET (P < 0.05). Furthermore, TS and the TS:TM ratio were 32% lower in DLHMTBA than in LMET (P < 0.05). L-MetInc was 42% lower in DLMET and DLHMTBA than in L-Met-deficient Control pigs, whereas plasma AA and hepatic mRNA abundances were similar among DL-HMTBA-, L-Met-, and DL-Met-supplemented pigs.Conclusions: In piglets, DL-HMTBA compared with L-Met and DL-Met supplementation increases RM and reduces the TS rate to conserve L-Met, but all 3 Met isomers support growth at a comparable rate. [ABSTRACT FROM AUTHOR]

The d-isomer of Met cannot be used directly by the mammary gland in dairy cows; instead, it is transformed into l-Met, the proteogenic isomer, in the liver and other extramammary tissues. It remains unclear whether different Met forms and a Met hydroxy analog, 2-hydroxy-4-(methylthio)butanoic acid (HMB), are metabolized and function similarly in the liver. The objective of the present study was to examine the regulation of key genes in Met regeneration, transulfuration, and transmethylation pathways in response to increasing doses of different Met forms. Hepatocytes isolated from 4 calves between 4 and 7 d old were maintained as monolayer cultures for 24 h before addition of treatments. Treatments of (0, 10, 20, 40 μM) d-Met, l-Met, dl-Met, dl-HMB, or a 1:1 mixture of dl-Met and dl-HMB were added to Met-free medium in triplicate. After 24 h, cell lysates were collected for quantification of gene expression by quantitative PCR, and mRNA abundance was normalized to the mean of 3 reference genes. Data were analyzed with PROC MIXED of SAS 9.3 (SAS Institute Inc., Cary, NC). Analyses of covariance confirmed equivalent slopes of Met form, and the final model included form, dose, and random effect of calf within form. Data are reported as least squares means ± standard error. No main effect of Met form was observed for any genes examined. The enzymes encoded by betaine-homocysteine methyltransferase (BHMT) and 5-methyltetrahydrofolate-homocysteine methyltransferase use betaine and 5-methyltetrahydrofolate, respectively, to regenerate Met from homocysteine. Increasing concentration of Met did not alter 5-methyltetrahydrofolate expression, but decreased BHMT expression. Expression of glycine N-methyltransferase, the enzyme that controls transmethylation flux from S-adenosyl-methionine, was not affected by Met concentration. Methionine concentration had no effect on expression of cystathionine β-synthase, a key enzyme for the transulfuration pathway. The decrease in BHMT expression indicates a decreased need for cellular Met regeneration with increasing Met concentration, independent of Met form. The lack of differences among Met forms on regulating genes examined indicates that all Met forms similarly reduced genes controlling Met regeneration and metabolism in primary bovine hepatocytes. [ABSTRACT FROM AUTHOR]

Insufficient supply of Met and choline (Chol) around parturition could compromise hepatic metabolism and milk protein synthesis in dairy cows. Mechanistic responses associated with supply of Met or Chol in primary liver cells enriched with hepatocytes (PHEP) from cows have not been thoroughly ascertained. Objectives were to isolate and culture PHEP to examine abundance of genes and proteins related to transmethylation, transsulfuration, and cytidine 5′-diphosphocholine (CDP-choline) pathways in response to Met or Chol. The PHEP were isolated from liver biopsies of Holstein cows (160 d in lactation). More than 90% of isolated cells stained positively for the hepatocyte marker cytokeratin 18. Cytochrome P450 (CYP1A1) mRNA abundance was only detectable in the PHEP and liver tissue compared with mammary tissue. Furthermore, in response to exogenous Met (80 μM vs. control) PHEP secreted greater amounts of albumin and urea. Subsequently, PHEP were cultured with Met (40 μM) or Chol (80 mg/dL) for 24 h. Compared with control or Chol, mRNA and protein abundance of methionine adenosyltransferase 1A (MAT1A) and phosphatidylethanolamine methyltransferase (PEMT) were greater in PHEP treated with Met. The mRNA abundance of S-adenosylhomocysteine hydrolase (SAHH), betaine-homocysteine methyltransferase (BHMT), and sarcosine dehydrogenase (SARDH) was greater in Met-treated PHEP compared with control or Chol. Compared with control, greater expression of 5-methyltetrahydrofolate- homocysteine methyltransferase (MTR), betaine aldehyde dehydrogenase (BADH), and choline dehydrogenase (CHDH) was observed in cells supplemented with Met and Chol. However, Chol led to the greatest mRNA abundance of CHDH. Abundance of choline kinase α (CHKA), choline kinase β (CHKB), phosphate cytidylyltransferase 1 α (PCYT1A), and choline/ethanolamine phosphotransferase 1 (CEPT1) in the CDP-choline pathway was greater in PHEP treated with Chol compared with control or Met. In the transsulfuration pathway, mRNA and protein abundance of cystathionine β-synthase (CBS) was greater in PHEP treated with Met compared with control or Chol. Similarly, abundance of cysteine sulfinic acid decarboxylase (CSAD), glutamate-cysteine ligase, catalytic subunit (GCLC), and glutathione reductase (GSR) was greater in response to Met compared with control or Chol. Overall, these findings suggest that transmethylation and transsulfuration in dairy cow primary liver cells are more responsive to Met supply, whereas the CDPcholine pathway is more responsive to Chol supply. The relevance of these data in vivo merit further study. [ABSTRACT FROM AUTHOR]

A pre-processing method for the extraction of fatty acids from cereal grains is described. Ultrasound (sonication)-assisted extraction was compared to a static extraction method as the pre-processing method before gas chromatography mass spectrometry (GCMS) analysis of barley, sorghum and corn grain samples. Principal component analysis (PCA) was applied to identify patterns in the chromatographic data and classify the samples based on the extraction treatment (sonication vs static). The results of the PCA clearly distinguish between the sonication and static samples. It was observed that the ultrasound-assisted extraction impacted the chromatographs of the grain samples, a factor which simplifies the interpretation of the data. In addition, the results showed the ability of using multivariate technique such as PCA to improve data interpretation. [ABSTRACT FROM AUTHOR]

In this article, we describe a proof of concept of the potential use of a biocatalytic process for the functionalization of technical soda lignins from wheat straw through the selective acylation of primary hydroxy groups of lignin oligomers by acetate or hexanoate, thus preserving their free, unreacted phenols. The selectivity and efficiency of the method, although they depend on the structural complexity of the starting material, have been proven on model compounds. Applied to technical lignins, the acylation yield is only moderate, due to structural and chemical features induced by the industrial mode of preparation of the lignins rather than to the lack of efficiency of the method. However, most of the physicochemical properties of the lignins, including their antioxidant potential, are preserved, advocating the potential use of these modified lignins for industrial applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sarieddine, Hadjiefstathiou, Majira, Pion and Ducrot.)

Methionine partitioning between protein turnover and a considerable pool of transmethylation precursors is a critical process in the neonate. Transmethylation yields homocysteine, which is either oxidized to cysteine (i.e., transsulfuration), or is remethylated to methionine by folate- or betaine- (from choline) mediated remethylation pathways. The present investigation quantifies the individual and synergistic importance of folate and betaine for methionine partitioning in neonates. To minimize whole body remethylation, 4-8-d-old piglets were orally fed an otherwise complete diet without remethylation precursors folate, betaine and choline (i.e. methyl-deplete, MD-) (n=18). Dietary methionine was reduced from 0.3 to 0.2 g/(kg∙d) on day-5 to limit methionine availability, and methionine kinetics were assessed during a gastric infusion of [13C1]methionine and [2H3-methyl]methionine. Methionine kinetics were reevaluated 2 d after pigs were rescued with either dietary folate (38 μg/(kg∙d)) (MD + F) (n=6), betaine (235 mg/(kg∙d)) (MD + B) (n=6) or folate and betaine (MD + FB) (n=6). Plasma choline, betaine, dimethylglycine (DMG), folate and cysteine were all diminished or undetectable after 7 d of methyl restriction (P<.05). Post-rescue, plasma betaine and folate concentrations responded to their provision, and homocysteine and glycine concentrations were lower (P<.05). Post-rescue, remethylation and transmethylation rates were~70-80% higher (P<.05), and protein breakdown was spared by 27% (P<.05). However, rescue did not affect transsulfuration (oxidation), plasma methionine, protein synthesis or protein deposition (P>.05). There were no differences among rescue treatments; thus betaine was as effective as folate at furnishing remethylation. Supplemental betaine or folate can furnish the transmethylation requirement during acute protein restriction in the neonate. [ABSTRACT FROM AUTHOR]

Cystathionine-β-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes β-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5′-phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential step in glutathione synthesis. Redox homeostasis, free-radical detoxification and one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye-lens dislocation along with vascular cognitive impairment and dementia. HHcy results in retinovascular, coronary, cerebral and peripheral vessels' dysfunction and how it causes metabolic dysregulation predisposing patients to serious eye conditions remains unknown. HHcy orchestrates inflammation and redox imbalance via epigenetic remodeling leading to neurovascular pathologies. Although circular RNAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated. Progress in gene-centered analytics via improved microarray and bioinformatics are enabling dissection of genomic pathways however there is an acute under-representation of circular RNAs in ocular disorders. This study undertook circRNAs' analysis in the eyes of CBS deficient mice identifying a pool of 12532 circRNAs, 74 exhibited differential expression profile, ∼ 27% were down-regulated while most were up-regulated ( ∼ 73%). Findings also revealed several microRNAs that are specific to each circRNA suggesting their roles in HHcy induced ocular disorders. Further analysis of circRNAs helped identify novel parental genes that seem to influence certain eye disease phenotypes. [ABSTRACT FROM AUTHOR]

Lipid transmethylation methods described in the literature are not always evaluated with care so to insure that the methods are effective, especially on food matrix or biological samples containing polyunsaturated fatty acid (PUFA). The aim of the present study was to select a method suitable for all lipid species rich in long chain n-3 PUFA. Three published methods were adapted and applied on individual lipid classes. Lipid (trans)methylation efficiency was characterized in terms of reaction yield and gas chromatography (GC) analysis. The acid-catalyzed method was unable to convert triglycerides and sterol esters, while the method using an incubation at a moderate temperature was ineffective on phospholipids and sterol esters. On the whole only the method using sodium methoxide and sulfuric acid was effective on lipid classes taken individually or in a complex medium. This study highlighted the use of an appropriate (trans)methylation method for insuring an accurate fatty acid composition. [ABSTRACT FROM AUTHOR]

Background Folate is required for synthesis of methyl groups and DNA in growing cells. The association between folate and prostate cancer (PCa) is not conclusive. Methods We investigated concentrations of folate vitamers, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in blood of men with PCa (n = 129) or benign prostatic hyperplasia (BPH) (n = 73) who were recruited just after the first diagnosis. Results In younger subjects <65 years, concentrations of (6S)-5-CH 3 -H 4 folate (15.3 vs. 17.7 nmol/L) or total folate (UPLC-MS/MS) (18.7 vs. 23.0 nmol/L) did not differ between men with BPH and those with PCa, while SAM was higher in the controls (128 vs. 116 nmol/L). Younger patients with low- and high grade cancer did not differ in (6S)-5-CH 3 -H 4 folate (17.8 vs. 17.3 nmol/L) or total folate (UPLC-MS/MS) (22.9 vs. 23.3 nmol/L), but SAM was lower in patients with low grade PCa (111 vs. 126 nmol/L). In the older group ≥65 years, (6S)-5-CH 3 -H 4 folate (18.4 vs. 18.2 nmol/L) and total folate (UPLC-MS/MS) (22.5 vs. 22.1 nmol/L) did not differ between BPH and PCa. Older patients with advanced tumors had lower (6S)-5-CH 3 -H 4 folate compared with those with low grade tumor (12.8 vs. 20.0 nmol/L: p = 0.013). Plasma SAM was not different between older patients and controls and was not related to PCa grade. Conclusions Lowered serum methyl folate measured at the time of diagnosis in older patients with advanced PCa, and lowered plasma SAM in younger patients with low grade PCa suggest differential folate metabolism that may have mechanistic, prognostic or predictive values. [ABSTRACT FROM AUTHOR]

According to the tissue-specific methylation database (doi: 10.1016/j.gene.2014.09.060), methylation at CpG locus cg03096975 in EML2 has been preliminarily proven to be specific to brain tissue. In this study, we enlarged sample size and developed a technique for identifying brain tissue in aged samples. Combined Bisulfite Restriction Analysis-for EML2 (COBRA-EML2) technique was established and validated in various organ samples obtained from 108 autopsies. In addition, this technique was also tested for its reliability, minimal DNA concentration detected, and use in aged samples and in samples obtained from specific brain compartments and spinal cord. COBRA-EML2 displayed 100% sensitivity and specificity for distinguishing brain tissue from other tissues, showed high reliability, was capable of detecting minimal DNA concentration (0.015ng/μl), could be used for identifying brain tissue in aged samples. In summary, COBRA-EML2 is a technique to identify brain tissue. This analysis is useful in criminal cases since it can identify the vital organ tissues from small samples acquired from criminal scenes. The results from this analysis can be counted as a medical and forensic marker supporting criminal investigations, and as one of the evidences in court rulings. [ABSTRACT FROM AUTHOR]

Several physiological functions of adenosine (Ado) appear to be mediated by four G protein-coupled Ado receptors. Ado is produced extracellularly from the catabolism of the excreted ATP, or intracellularly from AMP, and then released through its transporter. High level of intracellular Ado occurs only at low energy charge, as an intermediate of ATP breakdown, leading to hypoxanthine production. AMP, the direct precursor of Ado, is now considered as an important stress signal inside cell triggering metabolic regulation through activation of a specific AMP-dependent protein kinase. Intracellular Ado produced from AMP by allosterically regulated nucleotidases can be regarded as a stress signal as well. To study the receptor-independent effects of Ado, several experimental approaches have been proposed, such as inhibition or silencing of key enzymes of Ado metabolism, knockdown of Ado receptors in animals, the use of antagonists, or cell treatment with deoxyadenosine, which is substrate of the enzymes acting on Ado, but is unable to interact with Ado receptors. In this way, it was demonstrated that, among other functions, intracellular Ado modulates angiogenesis by regulating promoter methylation, induces hypothermia, promotes apoptosis in sympathetic neurons, and, in the case of oxygen and glucose deprivation, exerts a cytoprotective effect by replenishing the ATP pool. [ABSTRACT FROM AUTHOR]

Methionine adenosyltransferase (MAT) is a critical biological enzyme and that can catalyze L-met and ATP to form S-adenosylmethionine (SAM), which is acted as a biological methyl donor in transmethylation reactions involving histone methylation. However, the regulatory effect of methionine adenosyltransferase2A (MAT2A) and its associated methyltransferase activity on adipogenesis is still unclear. In this study, we investigate the effect of MAT2A on adipogenesis and its potential mechanism on histone methylation during porcine preadipocyte differentiation. We demonstrated that overexpression of MAT2A promoted lipid accumulation and significantly up-regulated the levels of adipogenic marker genes including PPARγ, SREBP-1c, and aP2. Whereas, knockdown of MAT2A or inhibition MATII enzyme activity inhibited lipid accumulation and down-regulated the expression of the above-mentioned genes. Mechanistic studies revealed that MAT2A interacted with histone-lysine N -methyltransferase Ezh2 and was recruited to Wnt10b promoter to repress its expression by promoting H3K27 methylation. Additionally, MAT2A interacted with MafK protein and was recruited to MARE element at Wnt10b gene. The catalytic activity of MAT2A as well as its interacting factor-MAT2B, was required for Wnt10b repression and supplying SAM for methyltransferases. Moreover, MAT2A suppressed Wnt10b expression and further inhibited Wnt/β-catenin signaling to promote adipogenesis. [ABSTRACT FROM AUTHOR]

Diet-related bioactive compounds are intensively examined in vitro, although the in vivo and in vitro effects are different, and the mode of actions in in vivo is not yet known in detail. Metals are also important both in the free radical formation and in the antioxidant defence as well as in signal transduction. It is a proven fact that methylation agents have an important role in preventing cancer and improve redox homeostasis. The root of Beta vulgaris L. ssp . esculenta var. rubra (table beet) as a functional food has been used for centuries as a traditional and popular food in many national dishes. Since several bioactive agents e.g. betaine, betanins, betacyanins, betaxanthins, vulgaxanthine, polyphenols, flavonoids, vitamins (thiamine, riboflavine, piridoxine, ascorbic acid, biotin and folic acid) as well as soluble fibre, pectin and different metal elements (e.g. Al, B, Ba, Ca, Cu, Fe, K, Mg, Mn, Na, Zn) can be found in large quantities in vegetable table beet, therefore a relative simple methodological repertoire to interpret the impact of variety of active substances on the vital function of the metastatic cancerous patients is needed to be developed. It is also required to examine in addition to routine laboratory parameters, values of HbA1c, 9 cytokines and levels of 3 growth factors, the global parameter of redox-homeostasis, few metal elements and levels of free and Zn-protoporphyrins as well as transmethylation, since low transmethylation ability, high free protoporphyrin and Zn-protoporphyrin concentrations and high induced free radical levels of erythrocytes are very important indexes in cancer. [ABSTRACT FROM AUTHOR]

S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways. Also included in this review are the present-day applications of SAMe in the treatment in these diseases in each age group. [ABSTRACT FROM AUTHOR]

The reaction of [W(N-2,6-iPr2C6H3)(CHCMe2Ph)(OTf)2(DME)] (DME = 1,2-dimethoxyethane, OTf = CF3SO3) with the N-heterocyclic carbene (NHC) 1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene (IMesH2) leads to DME activation followed by transmethylation and in due consequence to the formation of the N-heterocyclic olefin complex [W(N-2,6-iPr2C6H3)(CHCMe2Ph)(OTf)2(IMesH2CH2)] along with [W(N-2,6-iPr2C6H3)(CHCMe2Ph)(OTf)(IMesH2)(κ2-O(CH2)2OMe)], [1,3-bis(2,4,6-trimethylphenyl)-2-methylimidazolidinium+ (OTf−)] and [1,3-bis(2,4,6-trimethylphenyl)-2-H-imidazolidinium+ (OTf−)]. A reaction pathway is proposed and confirmed by the use of 13C-labelled compounds; structures of the products were verified by NMR and/or single-crystal X-ray analysis. [ABSTRACT FROM AUTHOR]

This study sought to develop a cost-effective biological catalysis process for S -adenosyl- l -methionine (SAM) production. During the process, a mixture of d -methionine ( d -Met) and l -methionine ( l -Met), namely dl -Met, was used as substrate to replace the conventional but expensive pure l -Met. The concentration of dl -Met in substrate was optimized. When 80 g/L of dl -Met was added in a 5 L-scale bioreactor, 13.74 g/L of SAM was produced with an l -Met conversion rate of 32.15%. The fermentation process was then scaled up to meet the requirements of realistic industrial SAM production. In a 300 L-scale fermentation process, 10.45 g/L of SAM was achieved, with an l -Met conversion rate of 32.61%. Moreover, the proportion of d -Met remaining in broth increased from 50% at the beginning to 76.89% at the end of fermentation. The fermentation process is generally appropriate for commercial SAM production. [ABSTRACT FROM AUTHOR]