S-Adenosylmethionine-dependent Protein Methylation Is Required for Expression of Selenoprotein P and Gluconeogenic Enzymes in HepG2 Human Hepatocytes

Jackson, Matthew I.; Cao, Jay; Zeng, Huawei; Uthus, Eric O.; Combs, Gerald F.

doi:10.1074/jbc.m112.412932

Cited by 25 publications

(22 citation statements)

References 44 publications

(58 reference statements)

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“…1,2 In this role, SAM is also involved in metabolic process regulation through contributing to nucleic acid 3 and protein methylation reactions. 4,5 In a different role, SAM is found as a central cofactor or cosubstrate in the enzyme family of radical SAM enzymes. 6 These enzymes catalyse a broad set of radical reactions, from C-C bond formations, [7][8][9] to complex skeleton rearrangements [10][11][12][13][14] (see also Ref 15 for an extensive review and references therein).…”

Section: Introductionmentioning

confidence: 99%

Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine

Bame

Hoeck

Carrington

et al. 2018

Phys. Chem. Chem. Phys.

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The use of molecular dynamics (MD) calculations to derive relative populations of conformers is highly sensitive to both timescale and parameterisation of the MD. Where these calculations are coupled with NOE data to determine the dynamics of a molecular system, this can present issues if these populations are thus relied upon. We present an approach that refines the highly accurate PANIC NMR methodology combined with clustering approaches to generate conformers, but without restraining the simulations or considering the relative population distributions generated by MD. Combining this structural sampling with NOE fitting, we demonstrate, for S-adenosylmethionine (aqueous solution at pH 7.0), significant improvements are made to the fit of populations to the experimental data, revealing a strong overall preference for the syn conformation of the adenosyl group relative to the ribose ring, but with less discrimination for the conformation of the ribose ring itself.

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Section: Introductionmentioning

confidence: 99%

Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine

Bame

Hoeck

Carrington

et al. 2018

Phys. Chem. Chem. Phys.

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“…The association of arsenic metabolism with diabetes could also be related to one-carbon metabolism because S-adenosylmethionine (SAM) is the methyl donor for arsenic metabolism (24,64). Experimental evidence has shown that SAM plays an important role in lipogenesis and in the development of diabetes (26,65,66). An in vitro study in Caenorhabditis elegans, an experimental model for human diseases and metabolic pathways (67,68), found that the synthesis of SAM regulated the expression of genes required for adequate lipid metabolism (65).…”

Section: Discussionmentioning

confidence: 99%

“…An in vitro study in Caenorhabditis elegans, an experimental model for human diseases and metabolic pathways (67,68), found that the synthesis of SAM regulated the expression of genes required for adequate lipid metabolism (65). In HepG2 human hepatocytes, the optimal balance between SAM and S-adenosylhomocysteine is critical to maintain appropriate expression of gluconeogenic enzymes (66). In addition, in a cross-sectional study of 50-75-year-old adults from the Netherlands (n = 648), plasma SAM was positively associated with fat mass and truncal adiposity, although reverse causation could not be excluded (69).…”

Section: Discussionmentioning

confidence: 99%

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

Howard¹,

Umans²,

Gribble³

et al. 2014

ISEE Conference Abstracts

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Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45-75 years were recruited in 1989-1991 and followed through 1998-1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ‡126 mg/dL, 2-h glucose ‡200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63-0.93) and 0.82 (0.73-0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism. Humans are exposed to inorganic arsenic (iAs) through drinking water, food, dust, and ambient air (1). Increasing epidemiologic and experimental evidence supports a role for iAs in the development of diabetes (2,3). At high arsenic levels (.150 mg/L in drinking water), evidence from Taiwan and Bangladesh supports an association with diabetes, although most studies are cross-sectional and concerns exist about the measures of arsenic exposure and definition of diabetes used in some studies (2,4). At low-moderate arsenic levels, evidence from Mexico and the

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“…In diabetic subjects, β-cell apoptosis seems to be more of a deciding factor than replication in controlling the cell mass compared with control subjects [38]. Selenoprotein (SelP), a secretory protein primarily produced by the liver and regulated similar to that of the gluconeogenic enzyme glucose 6-phosphatase [39], by concerted action of peroxisome proliferator-activated receptor co activator 1α (PPAR-1α) and the transcription hepatocyte nuclear factor-4α [40]. It has been shown a positive correlation between hepatic SelP mRNA levels and insulin resistance in humans, a long with a positive correlation between serum SelP levels and both fasting plasma glucose and hemoglobin A1C (HbA1c) levels.…”

Section: Selenium In T2d Pathogenesismentioning

confidence: 99%

Trace Elements Modulates Oxidative Stress in Type 2 Diabetes

Gouaref¹,

Koceir²

2018

Diabetes Food Plan

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The relationship between antioxidant trace elements (ATE) and metabolic disease is subtle and complex due to overproduction of reactive oxygen species (ROS). In type 2 diabetes (T2D), the relationship between ATE and insulin-like trace elements is very complex during oxidative stress (OS), being mediated by hyperglycemia, dyslipidemia and inflammation. The important role assigned to ATE (zinc, selenium, copper, manganese and chromium) by their involvement at different levels: Hemodynamic homeostasis (endothelial function and protein glycation), energy metabolism (carbohydrate and lipid tolerance) and enzymatic antioxidant protection [superoxide dismutase (SOD), glutathione peroxidase (GPx)]. The ROS-mediated cellular signaling process is crucial. Manganese and selenium levels abnormalities might to be useful indicators of oxidative damage. Two major factors were suggested: lack of Mn bioavailability leading to the decrease of mitochondrial SOD activity (cytosolic SOD remains active), and low blood selenium level implying a decrease in GPx activity. In T2D pathophysiology, it appears that antioxidant defense is preserved in the cytosol (Cu/Zn-SOD) in T2D, whereas it is impaired in mitochondria (Mn-SOD) in the three pathologies, which make this cell organelle a true ATE therapeutic target. Future challenges require the in-depth investigations of mitochondrial mechanisms, involved the antioxidant trace elements signaling pathways in T2D pathophysiology.

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S-Adenosylmethionine-dependent Protein Methylation Is Required for Expression of Selenoprotein P and Gluconeogenic Enzymes in HepG2 Human Hepatocytes

Cited by 25 publications

References 44 publications

Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine

Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

Trace Elements Modulates Oxidative Stress in Type 2 Diabetes

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