The impact of common genetic variants in the mitochondrial glycine cleavage system on relevant metabolites

O’Reilly, J. M.; Pangilinan, Faith; Hokamp, Karsten; Ueland, Per Magne; Brosnan, John T.; Brosnan, Margaret E.; Brody, Lawrence C.; Molloy, Anne M.

doi:10.1016/j.ymgmr.2018.05.006

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…Simultaneously, GLDC can also catalyze the reverse reaction, i.e., the conversion of serine to glycine that is dependent on folate ester. Accordingly, GLDC is primarily involved in the cellular metabolism of amino acids and affects glycolysis, pyrimidine synthesis, and other metabolic pathways [ 30 , 31 ]. The biological functions of GLDC in organisms are mostly related to processes of amino acid metabolism, such as protein composition, as well as the basic structure of several important substances, including methionine, choline, some important hormones, and deoxyribonucleic acid [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Glycine Decarboxylase Suppresses the Renal Cell Carcinoma Growth and Regulates Its Gene Expressions and Functions

Chen¹,

Gao²,

Wang³

et al. 2022

World J Oncol

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Background: Glycine decarboxylase (GLDC), a key metabolic enzyme, participates in the regulation of the glycine metabolic pathway. Differential expression of GLDC is linked to the malignant growth of renal cell carcinoma (RCC) and may regulate tumor progression through other genes. However, the regulatory function of GLDC in RCC is currently unknown. The purpose of this work was to evaluate the roles of GLDC in the invasion, proliferation, and migration of RCC cells and elucidate the processes underlying RCC development. Methods:The expression of GLDC in RCC cell lines and tissues was identified by quantitative reverse transcription polymerase chain reaction (PCR) and western blot. A stably transfected cell line overexpressing GLDC was constructed using a lentiviral vector. Cell proliferation was detected using Cell Counting Kit-8 (CCK8) and EdU experiments, and scratch and transwell assays were used to determine migration and invasion capabilities. Furthermore, differential proteins were identified and obtained using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) analysis. Finally, these differential proteins were analyzed by bioinformatics, including cluster analysis, subcellular localization, domain annotation, annotation of the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), enrichment analysis, and study of protein-protein interactions.Results: GLDC expression was found to be lower in six RCC cell lines (786-O, A498, Caki-1, 769-P, OSRC-2, and ACHN) than in 293T cells and decreased in kidney cancer tissues compared to neighboring normal tissues. Overexpression of GLDC inhibited the proliferation of RCC cells as well as their migration and invasion abilities. Tandem mass tag analysis showed that 317 and 236 genes were downregulated and upregulated, respectively, when GLDC was overexpressed in A498 cells. Tandem mass tag analysis showed that 317 and 236 genes were downregulated and upregulated, respectively, when GLDC was overexpressed in A498 cells. Volcano plot showed these upregulated and downregulated proteins. Cluster analysis showed that differentially expressed protein screening can represent the effect of biological treatment on samples. Subcellular localization analysis showed differential proteins are mainly distributed in the nucleus, cytoplasm, mitochondria, plasma membrane, extracellular matrix, and lysosome. GO annotation showed many biological processes in the cells were changed, including "positive regulation of histone H3-K4 methylation", "cofactor binding", and "nuclear body". KEGG pathway analysis showed key pathways have all undergone considerable alterations, such as "cell cycle", "glyoxylate and dicarboxylate metabolism", and "threonine, glycine, and serine metabolism". Finally, highly aggregated proteins with the same or similar functions were acquired by analysis of the protein-protein interaction (PPI) network. Conclusions:These studies indicate that GLDC overexpression suppresses the invasion, proliferation, and migration of R...

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Section: Discussionmentioning

confidence: 99%

Glycine Decarboxylase Suppresses the Renal Cell Carcinoma Growth and Regulates Its Gene Expressions and Functions

Chen¹,

Gao²,

Wang³

et al. 2022

World J Oncol

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“…Other than intake in the diet, the transport, synthesis and metabolism of MI represent multiple possible points at which inositol status could be modulated by functional variation in the molecular mediators of these processes. The combination of biochemical assays with genome-wide association studies offers potential to identify genetic determinants of nutrient status (33)(34)(35). In the current study, we adapted mass spectrometry-based methodology to enable high throughput quantification of inositol in plasma and examined potential genetic associations with plasma MI.…”

Section: O R I Gmentioning

confidence: 99%

“…Serum methylmalonic acid and homocysteine were measured by automated isotope-dilution GC-MS as previously described (33), with inter-assay CVs of 8.1% and 2.2%, respectively. Formate (inter-assay variance of 7.4%) was measured in serum by GC-MS, as previously described (35).…”

Section: Biochemical Analysesmentioning

confidence: 99%

Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

Weston

Pangilinan

Eaton

et al. 2022

The Journal of Nutrition

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Background Myo-inositol (MI) is incorporated into numerous biomolecules, including phosphoinositides and inositol phosphates. Disturbance of inositol availability or metabolism is associated with various disorders, including neurological conditions and cancers, while supplemental MI has therapeutic potential in conditions such as depression, polycystic ovary syndrome and congenital anomalies. Inositol status may be influenced by diet, synthesis, transport, utilisation and catabolism. Objectives We aimed to investigate potential genetic regulation of circulating MI status and to evaluate correlation of MI concentration with other metabolites. Methods Gas chromatography mass spectrometry was used to determine plasma MI concentration of more than 2,000 healthy, young adults (aged 18–28 years) from the Trinity Student Study. Genotyping data was used to test association of plasma MI with SNPs in candidate genes, encoding inositol transporters and synthesising enzymes, and test for genome-wide association. We evaluated potential correlation of plasma MI with D-chiro inositol, glucose and other metabolites by Spearman's rank correlation. Results Mean plasma MI showed a small but significant difference between males and females (28.5 and 26.9 µM, respectively). Candidate gene analysis revealed several nominally significant associations with plasma MI, most notably for SLC5A11, encoding a sodium-coupled inositol transporter, also known as SMIT2 (sodium-dependent myo-inositol transporter 2). However, these did not survive correction for multiple testing. Subsequent testing for genome-wide association with plasma MI did not identify associations of genome-wide significance (p < 5 × 10–8). However, 8 SNPs exceeded the threshold for suggestive significant association with plasma MI concentration (p < 1 × 10–5), 3 of which were located within or close to genes: MTDH, LAPTM4B and ZP2. We found significant positive correlation of plasma MI concentration with concentration of D-chiro-inositol and several other biochemicals including glucose, methionine, betaine, sarcosine and tryptophan. Conclusion Our findings suggest potential for modulation of plasma MI in young adults by variation in SLC5A11 which is worthy of further investigation.

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In‐situ Glycine Sensor Development Based ZnO/Al₂O₃/Cr₂O₃ Nanoparticles

et al. 2018

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Initially, low‐dimensional ternary nanoparticles of ZnO/Al2O3/Cr2O3 were synthesized using reliable solvothermal process and successfully implemented to fabricate enzyme‐less selective glycine (Gly) sensor. The calibration curve was plotted from the linear relation of current versus concentration of glycine. By using the slope of resultant calibration curve, the sensitivity (2.09*102 μAμM−1cm−2) of Gly sensor was estimated by considering the active surface area of fabricated sensor probe. The proposed enzyme‐free Gly biosensor was found linear over large concentration range of 0.1 nM ∼ 1.0 μM, known as linear dynamic range (LDR). The detection limit (82.25±4.11 pM) was calculated at signal to noise ratio of 3 from the calibration curve. The proposed enzyme‐less Gly sensor was exhibited good reproducibility, long‐term stability and efficiency to detect Gly in real biological samples by electrochemical approach. Thus, this novel research methodology might be a good technique for the development of enzyme‐less sensor using ternary metal oxide nanoparticles onto GCE for the biomedical applications.

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The impact of common genetic variants in the mitochondrial glycine cleavage system on relevant metabolites

Cited by 6 publications

References 23 publications

Glycine Decarboxylase Suppresses the Renal Cell Carcinoma Growth and Regulates Its Gene Expressions and Functions

Glycine Decarboxylase Suppresses the Renal Cell Carcinoma Growth and Regulates Its Gene Expressions and Functions

Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

In‐situ Glycine Sensor Development Based ZnO/Al₂O₃/Cr₂O₃ Nanoparticles

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The impact of common genetic variants in the mitochondrial glycine cleavage system on relevant metabolites

Cited by 6 publications

References 23 publications

Glycine Decarboxylase Suppresses the Renal Cell Carcinoma Growth and Regulates Its Gene Expressions and Functions

Glycine Decarboxylase Suppresses the Renal Cell Carcinoma Growth and Regulates Its Gene Expressions and Functions

Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

In‐situ Glycine Sensor Development Based ZnO/Al2O3/Cr2O3 Nanoparticles

Contact Info

Product

Resources

About

In‐situ Glycine Sensor Development Based ZnO/Al₂O₃/Cr₂O₃ Nanoparticles