• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.1-9
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• 2016

Newborn screening (NBS) is important if early intervention is effective in a disorder and if there are sensitive and specific biochemical markers to detect disorder. Methionine is a useful marker to detect abnormal methionine-homocysteine metabolism, especially homocystinuria which needs urgent medical intervention. However, hypermethioninemia could occur in other metabolic disorder including liver disease, tyrosinemia type I, methionine adenosyltransferase (MAT) I/III deficiency, glycine N-methyltransferase (GNMT) deficiency, or adenosylhomocysteine hydrolase deficiency. However, experience with NBS for homocystinurias and methylation disorders is limited. Especially, MAT I/III deficiency which is the most common cause of persistent hypermethioninemia have two inheritance, autosomal recessive (AR) and autosomal dominant (AD), and their clinical manifestation is different between AR and AD. Here, author reviewed recent articles of guideline and proposed guideline for homocystinuria and methylation disorder.

• Microbiology and Biotechnology Letters
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• v.42 no.1
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• pp.11-17
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• 2014

Selenium is an essential trace element for mammals, but it is very toxic. Therefore, the control of selenium concentrations should be precisely and effectively monitored. Selenium is naturally obtained through foods and seleno-L-methionine (LSeMet) is a major form of selenium. It has been reported that L-SeMet is only converted into Se-adenosyl-L-SeMet. However, a recent study suggested that L-SeMet was directly metabolized into methylselenol ($CH_3SeH$) in mouse liver extract by the reaction of cystathionine ${\gamma}$-lyase (CGL). The canonical reaction of CGL was known to catalyze the cleavage of L-cystathionine to L-cysteine, ${\alpha}$-ketobutyrate and $NH_3$. In the present study, we found that L-SeMet could be directly converted to $CH_3SeH$ using purified homogenous human CGL instead of mouse liver cytosol. Authentic $CH_3SeH$ was prepared by reduction of dimethyldiselenide with sodium tetrahydroborate. The gaseous product of the enzymatic reaction with L-SeMet was analyzed by GC/MS spectrometry. The GC/MS data was identical to that of authentic dinitrophenyl selenoether. We also analyzed the kinetic parameters for the formation of $CH_3SeH$ from L-SeMet by human and mouse CGL. These results suggest that human CGL is a critical enzyme which is responsible for L-SeMet metabolism.

• Journal of Microbiology and Biotechnology
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• v.18 no.8
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• pp.1368-1376
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• 2008

In our previous study, the expression of active H-ferritins in Saccharomyces cerevisiae was found to reduce cell growth and reactive oxygen species (ROS) generation upon exposure to oxidative stress; such expression enhanced that of high-affinity iron transport genes (FET3 and FTR1). The results suggested that the recombinant cells expressing H-ferritins induced cytosolic iron depletion. The present study analyzes metabolic changes under these circumstances via proteomic methods. The YGH2 yeast strain expressing A-ferritin, the YGH2-KG (E62K and H65G) mutant strain, and the YGT control strain were used. Comparative proteomic analysis showed that the synthesis of 34 proteins was at least stimulated in YGH2, whereas the other 37 proteins were repressed. Among these, the 31 major protein spots were analyzed via nano-LC/MS/MS. The increased proteins included major heat-shock proteins and proteins related to endoplasmic reticulum-associated degradation (ERAD). On the other hand, the proteins involved with folate metabolism, purine and methionine biosynthesis, and translation were reduced. In addition, we analyzed the insoluble protein fractions and identified the fragments of Idh1p and Pgk1p, as well as several ribosomal assembly-related proteins. This suggests that intracellular iron depletion induces imperfect translation of proteins. Although the proteins identified above result from changes in iron metabolism (i.e., iron deficiency), definitive evidence for iron-related proteins remains insufficient. Nevertheless, this study is the first to present a molecular model for iron deficiency, and the results may provide valuable information on the regulatory network of iron metabolism.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.406-410
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• 2013

Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

• Animal Bioscience
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• v.35 no.10
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• pp.1556-1565
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• 2022

Objective: Tan lambs (n = 36, 3 mo old, 19.1±0.53 kg) were used to assess effects of dietary guanidinoacetic acid (GAA) and rumen-protected methionine (RPM) on growth performance, carcass traits, meat quality, and serum parameters. Methods: Lambs were randomly assigned to three treatment groups, with 6 pens per group and 2 lambs per pen. Dietary treatments were: basal diet alone (I); basal diet supplemented with 0.08% GAA+0.06% RPM (II); and basal diet supplemented with 0.08% GAA+0.08% RPM (III). Diets were provided three times a day for 90 d. Intake per pen was recorded daily and individual lamb body weight (BW) was measured monthly. Carcass traits were measured after slaughter and meat quality at the end of the experiment, blood samples were taken on a subgroup of lambs for analysis of indicators mostly related to protein metabolism. Results: Final BW and average daily gain for the first and second month, and for the entire experiment were greater in Treatment II compared to Treatment I (p<0.05), whereas feed to gain ratio was lower (p<0.05). Treatment II had the optimal dressing percentage and net meat weight proportion, as well as crude protein and intramuscular fat concentrations in muscles. Treatment II improved meat quality, as indicated by the greater water holding capacity, pH after 45 min and 48 h, and lower shear force and cooking loss. Dietary supplementation of GAA and RPM also increased the meat color a^* and b^* values at 24 h. Finally, Treatment II increased total protein, and serum concentrations of albumin and creatinine, but decreased serum urea nitrogen concentrations, indicating improved protein efficiency. Conclusion: In this study, 0.08% GAA+0.06% RPM supplementation improved growth performance and meat quality of Tan lambs.

• Journal of Life Science
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• v.34 no.8
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• pp.588-593
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• 2024

An extensive analysis of 3,490 metabolic pathways in 471 archaebacterial species was conducted using the MetaCyc database. The number of metabolic pathways in these species varied significantly, ranging from 13 to 184 per species. Notably, no single metabolic pathway was found to be common in all archaebacteria. However, the "UTP and CTP de novo biosynthesis" and "tRNA charging" pathways were present in the 470 species. Among the top 12 most prevalent metabolic pathways in archaebacteria, five were associated with nucleic acids and five with proteins. The remaining pathways included the "synthetic pathway of S-adenosyl-L-methionine (SAM)," a critical cofactor in various bioreactions, and "phosphopantothenate biosynthesis III (archaea)," which is required for essential post-translational modifications. These findings underscore the importance of nucleic acids and protein metabolism in archaeal biology. When the average and standard deviation of the distance values obtained from the phylogenetic tree of metabolic pathways, each class of archaebacteria was divided into main two groups and the others, showing that the distribution of metabolic pathways was diverse. This study's insights hold potential applications in both foundational science and drug development.

• Journal of Society of Preventive Korean Medicine
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• v.11 no.1
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• pp.45-53
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• 2007

Homocysteine is a sulfur amino-acid produced during the metabolism of the essential amino acid methionine. Moderately increased plasma total homocysteine concentration have been implicated as a risk factor for occlusive vascular disease. Smoking is known to be one of the most significant factors leading to elevated plasma homocysteine concentration. However, the main component of a cigarette, nicotine has been not studied whether it is linked directly to the increase of homocysteine concentration in blood. The metabolism of homocysteine is closely linked to that of its cofactors, folate. Here, the effects of nicotine and folic acid on amount of plasma homocysteine were studied. The concentration of homocysteine was increased by about 70% in rat plasma after nicotine treatment for one month. This increased concentration of homocysteine was reduced by about 60% at 6 hours later after folate treatment. Thus, nicotine should be directly involved in increasing the concentration of plasma homocysteine. Also it is suggested that these results can be and applied and used for controlling withdrawal symptoms after stopping smoking as one of oriental medicine formulas.

• Molecules and Cells
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• v.37 no.12
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• pp.888-898
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• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.198-204
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• 2004

Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used $^{18}F$-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. $[^{11}C]Thymidine$ was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of $^{11}C$ and rapid metabolism of $[^{11}C]Thymidine$ in vivo make the radiotracer less suitable for routing use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicing but the image qualify and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog $3'-deoxy-3'-^{18}F-fluorothymidine$ (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. $[^{18}F]FLT$ is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. $[^{18}F]FLT$ PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and $[^{11}C]choline$, which is a new marker for cellular proliferation.

• Proceedings of the Korean Society for Applied Microbiology Conference
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• 2000.04a
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• pp.208-213
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• 2000

Penicillium fellutanum produces a phosphorylated, choline-containing extracellular peptido-polysaccharide, peptidophosphogalactomannan (pPxGM) (8). The $\^$13/C-methyl labeled pPxGM ([methyl-$\^$13/C]pPxGM) was prepared from the cultures supplemented with L-[methyl-$\^$13/C]methionine or [2-$\^$13/C]glycine and was used as a probe to monitor the fate of phosphocholine in this polymer. Addition of purified [methyl-$\^$l3/C]pPxGM to growing cultures in low phosphate medium resulted in the disappearance of [methyl-$\^$13/C]phosphocholine and -N,N'-dimethyl-phosphoethanolamine from the added [methyl-$\^$13/C]pPxGM. Two $\^$l3/C-methyl-enriched cytoplasmic solutes, choline-O-sulfate and glycine betaine, were found in mycelial extracts, suggesting that phosphocholine-containing extracellular pPxGM of P.fellutanum is a precursor of intracellular choline-O-sulfate and glycine betaine and thus of phosphatydilcholine (l0). $\^$13/C-Methyl-labeled cells grown in 3 M NaCl-containing medium showed 2.6- and 22-fold more accumulation of $\^$13/C-methyl labeled choline-O-sulfate and glycine betaine, respectively, originated from the extracellular [$\^$13/C-methyl]pPxGM than those grown without added NaCl. The results suggest that, in addition to glycerol and erythritol, glycine betaine and choline-O-sulfate and thus choline are also osmoprotectants and hence that pPxGM is involved in osmotolerance of this fungus (11). Taken collectively, the $\^$l3/C- and $\^$31/P-NMR analyses of cytosolic solute pools and structural modulation of extracellular pPxGM corresponding to environmental stimuli in P. fellutanum, provided evidence that pPxGM is involved in cellular choline metabolism, osmotolerance, and recycling of metabolites.