• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.29-38
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• 2018

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.19-27
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• 2007

An important potential of metabolomics-based approach is the possibility to develop fingerprints of diseases or cellular responses to classes of compounds with known common biological effect. Such fingerprints have the potential to allow classification of disease states or compounds, to provide mechanistic information on cellular perturbations and pathways and to identify biomarkers specific for disease severity and drug efficacy. Metabolic profiles of biological fluids contain a vast array of endogenous metabolites. Changes in those profiles resulting from perturbations of the system can be observed using analytical techniques, such as NMR and MS. $^1H$ NMR was used to generate a molecular fingerprint of serum or urinary sample, and then pattern recognition technique was applied to identity molecular signatures associated with the specific diseases or drug efficiency. Several metabolites that differentiate disease samples from the control were thoroughly characterized by NMR spectroscopy. We investigated the metabolic changes in human normal and clinical samples using $^1H$ NMR. Spectral data were applied to targeted profiling and spectral binning method, and then multivariate statistical data analysis (MVDA) was used to examine in detail the modulation of small molecule candidate biomarkers. We show that targeted profiling produces robust models, generates accurate metabolite concentration data, and provides data that can be used to help understand metabolic differences between healthy and disease population. Such metabolic signatures could provide diagnostic markers for a disease state or biomarkers for drug response phenotypes.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.765-774
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• 2021

Although research on the osteal signaling pathway has progressed, understanding of gut microbial-dependent signaling pathways for metabolic and immune bone homeostasis remains elusive. In recent years, the study of gut microbiota has shed light on our understanding of bone homeostasis. Here, we review microbiota-mediated gut-bone crosstalk via bone morphogenetic protein/SMADs, Wnt and OPG/receptor activator of nuclear factor-kappa B ligand signaling pathways in direct (translocation) and indirect (metabolite) manners. The mechanisms underlying gut microbiota involvement in these signaling pathways are relevant in immune responses, secretion of hormones, fate of osteoblasts and osteoclasts and absorption of calcium. Collectively, we propose a signaling network for maintaining a dynamic homeostasis between the skeletal system and the gut ecosystem. Additionally, the role of gut microbial improvement by dietary intervention in osteal signaling pathways has also been elucidated. This review provides unique resources from the gut microbial perspective for the discovery of new strategies for further improving treatment of bone diseases by increasing the abundance of targeted gut microbiota.

• Genomics & Informatics
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• v.7 no.3
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• pp.168-170
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• 2009

The explosion in biological data resulting from high-throughput experiments requires new software tools to manipulate and display pathways in a way that can integrate disparate sources of information. A visual Java-based CAD tool for drawing and annotating biological pathways with semiautomatic image-processing features is described in this paper. The result of the image-editing process is an XML file for the appropriate links. This tool integrates the pathway images and XML file sources. The system has facilities for linking graphical objects to external databases and is capable of reproducing existing visual representations of pathway maps.

• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1200-1210
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• 2004

Metabolic flux analysis was established by adapting previous stoichiometric model developed during growth with cellulose to cell grown with cellobiose for further direct comparison of the bacterial metabolism. In carbon limitation with cellobiose, a shift from acetate-ethanol fermentation to ethanol-lactate fermentation is observed and the pyruvate overflow is much higher than with cellulose. In nitrogen limitation with cellobiose, the cellodextrin and exopolysaccharide overflows are much higher than on cellulose. In carbon and nitrogen saturation with cellobiose, the cellodextrin, exopolysaccharide, and free amino acids overflows reach the highest levels observed but all remain limited on cellulose. By completely shunting the cellulosome, the use of cellobiose allows to reach much higher carbon consumption rates which, in return, highlights the metabolic limitation of C. cellulolyticum. Therefore, the physical nature of the carbon source has a profound impact on the metabolism of C. cellulolyticum and most probably of other cellulolytic bacteria. For cellulolytic bacteria, the use of soluble carbon substrate must carefully be taken into consideration for the interpretation of results. Direct comparison of metabolic flux analysis from cellobiose and cellulose revealed the importance of cellulosome, phosphoglucomutase and pyruvate-ferredoxin oxidoreductase in the distribution of carbon flow in the central metabolism. In the light of these findings, future directions for improvement of cellulose catabolism by this bacterium are discussed.

• BMB Reports
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• v.47 no.11
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• pp.599-608
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• 2014

As the prevalence of obesity has increased explosively over the last several decades, associated metabolic disorders, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases, have been also increased. Thus, new strategies for preventing and treating them are needed. The nuclear peroxisome proliferator-activated receptors (PPARs) are involved fundamentally in regulating energy homeostasis; thus, they have been considered attractive drug targets for addressing metabolic disorders. Among the PPARs, $PPAR{\gamma}$ is a master regulator of gene expression for metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of the thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects, such as weight gain, fluid retention, and cardiovascular dysfunction. Recently, many reports have suggested that $PPAR{\gamma}$ could be modulated by post-translational modifications (PTMs), and modulation of PTM has been considered as novel approaches for treating metabolic disorders with fewer side effects than the TZDs. In this review, we discuss how PTM of $PPAR{\gamma}$ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of $PPAR{\gamma}$.

• BMB Reports
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• v.54 no.12
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• pp.626-631
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• 2021

Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3β, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTP-bound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.1-7
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• 2023

Inherited metabolic disorders (IMD) are a group of disorders involving various metabolic pathways. Genetic diagnosis of IMD has been challenging because of extremely heterogeneous nature and extensive laboratory and/or phenotype overlap. Conventional genetic diagnosis was a gene-by-gene approach that needs a priori information on the causative genes that might underlie the IMD. Recent implementation of next-generation sequencing (NGS) technologies has changed the process of genetic diagnosis from a gene-by-gene approach to simultaneous analysis of targeted genes possibly associated with the IMD using gene panels or using whole exome/genome sequencing (WES/WGS) covering entire human genes. Clinical NGS tests can be a cost-effective approach for the rapid diagnosis of IMD with genetic heterogeneity and are becoming standard diagnostic procedures.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.3
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• pp.171-177
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• 2002

The metabolic flux pattern for L-histidine production was analyzed when glucose and/or acetate were used as carbon sources. Total L-histidine production was enhanced when mixed substrate (glucose and acetate) was used, compared wish that when either glucose or acetate was used as the sole carbon source. Theoretical maximum carbon fluxes through the main pathways for L-histldine production, cell growth, and ATP consumption for cell maintenance were obtained by the linear programming (LP) method. By comparison of the theoretical maximum carbon fluxes tilth actual ones, it was found that a large amount of glucose was actually used for maintenance of cell viability. On the other hand, acetate was used for cell growth. After depletion of acetate in the mixed substrate culture, the flux for glucose to L-histldine synthesis was markedly enhanced. A strategy for effective L-histidine production using both carbon sources was proposed.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.6
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• pp.422-430
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• 2000

Mechanism of lignin biodegradation caused by basidiomycetes and the history of lignin biodegradation studies were briefly reviewed. The important roles of fungal extracellular ligninolytic enzymes such as lignin and manganese peroxidases (LiP and MnP) were also summarized. These enzymes were unique in their catalytic mechanisms and substrate specificities. Either LiP or MnP system is capable of oxidizing a variety of aromatic substrates via a one-electron oxidation. Extracellular fungal system for aromatic degradation is non-specific, which recently attracts many people working a bioremediation field. On the other hand, an intracellular degradation system for aromatic compounds is rather specific in the fungal cell. Structurally similar compounds were prepared and metabolized, indicating that an intracellular degradation strategy consisted of the cellular systems for substrate recognition and metabolic response. It was assumed that lignin-degrading fungi might be needed to develop multiple metabolic pathways for a variety of aromatic compounds caused by the action of non-specific ligninolytic enzymes on lignin. Our recent results on chemical stress responsible factors analyzed using mRNA differential display techniques were also mentioned.