• 한국자기공명학회논문지
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• 제12권1호
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• pp.14-25
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• 2008

To investigate the 3-bond connectivity of human brain metabolites by scalar coupling interaction through 2D-correlation spectroscopy (COSY) techniques using high field NMR spectroscopy. All NMR experiments were performed at 298K on Unity Inova 500 or 600 (Varian Inc.) equipped with a triple resonance probe head with z-shield gradient. Human brain metabolites were prepared with 10% $D_2O$. Two dimensional 2D COSY spectra were acquired with 4096 complex data points in $t_2$ and 128 or 256 increments in $t_1$ dimension. The spectral width was 9615.4 Hz and solvent suppression was achieved using presaturation using low power irradiation of the water resonance during 2s of relaxation delay. NMR data were processed using VNMRJ (Varian Instrument) software and all the chemical shifts were referenced to the methyl resonance of N-acetyl aspartate (NAA) peak at 2.0 ppm. Total 10 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), lactate (Lac), taurine (Tau), ${\gamma}$-aminobutyricacid (GABA), alanine (Ala) were included for major target metabolites. Symmetrical 2D-COSY spectra were successfully acquired. Total 14 COSY cross peaks were observed even though there were parallel/orthogonal noisy peaks induced by water suppression. Except for Cr, all of human brain metabolites produced COSY cross peaks. The spectra of NAA methyl proton at 2.02 ppm and Glu methylene proton ($CH_2(3)$) at 2.11 ppm and Gln methylene proton ($CH_2(3)$) at 2.14 ppm were overlapped in the similar resonance frequency between 2.00 ppm and 2.15 ppm. The present study demonstrated that in vitro 2D-COSY represented the 3-bond connectivity of human brain metabolites by scalar coupling interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2D-COSY study. Also it would be helpful to determine the molecular stereochemistry in vivo by using two-dimensional MR spectroscopy.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• 약학회지
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• 제32권1호
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• pp.50-54
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• 1988

A simple and sensitive method was studied for the simultaneous determination of catecholamine, indoleamine and their related metabolites by high performance liquid chromatography with electrochemical detector. Norepinephrine, dopamine, serotonin and their metabolites of 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-indoleacetic acid were resolved from rat brain tissue homogenates by separation on reversed phase $C_{18}$ column with mobile phase consisting of monochloroacetate buffer (pH2.47), 1.42mM sodium octyl sulfonate and 7% acetonitrile. Both catechols and indoles can be eluted in 15min. The sensitivities of this method are sufficient for determination of at least 100 pg of neurochemical amines in brain samples, for example, frontal cortex, olfactory bulb, striatum, septum, hippocampus, thalamus, hypothalamus, medulla & pons and cerebellum. The highest level of dopamine was observed in striatum whereas norepinephrine and serotonin were in hypothalamus.

• Molecules and Cells
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• 제43권3호
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• pp.276-285
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• 2020

Circadian rhythm is an endogenous oscillation of about 24-h period in many physiological processes and behaviors. This daily oscillation is maintained by the molecular clock machinery with transcriptional-translational feedback loops mediated by clock genes including Period2 (Per2) and Bmal1. Recently, it was revealed that gut microbiome exerts a significant impact on the circadian physiology and behavior of its host; however, the mechanism through which it regulates the molecular clock has remained elusive. 3-(4-hydroxyphenyl)propionic acid (4-OH-PPA) and 3-phenylpropionic acid (PPA) are major metabolites exclusively produced by Clostridium sporogenes and may function as unique chemical messengers communicating with its host. In the present study, we examined if two C. sporogenes-derived metabolites can modulate the oscillation of mammalian molecular clock. Interestingly, 4-OH-PPA and PPA increased the amplitude of both PER2 and Bmal1 oscillation in a dose-dependent manner following their administration immediately after the nadir or the peak of their rhythm. The phase of PER2 oscillation responded differently depending on the mode of administration of the metabolites. In addition, using an organotypic slice culture ex vivo, treatment with 4-OH-PPA increased the amplitude and lengthened the period of PER2 oscillation in the suprachiasmatic nucleus and other tissues. In summary, two C. sporogenes-derived metabolites are involved in the regulation of circadian oscillation of Per2 and Bmal1 clock genes in the host's peripheral and central clock machineries.

• 약학회지
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• 제43권1호
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

• Molecules and Cells
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• 제38권7호
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• pp.587-596
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• 2015

Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to the identification of disease biomarkers, with a number of well-known biomarkers identified. Metabolomics is a potent approach to unravel the intricate relationships between metabolism, obesity and progression to diabetes and, at the same time, has potential as a clinical tool for risk evaluation and monitoring of disease. Moreover, metabolomics applications have revealed alterations in the levels of metabolites related to obesity-associated diabetes. This review focuses on the part that metabolomics has played in elucidating the roles of metabolites in the regulation of systemic metabolism relevant to obesity and diabetes. It also explains the possible metabolic relation and association between the two diseases. The metabolites with altered profiles in individual disorders and those that are specifically and similarly altered in both disorders are classified, categorized and summarized.

• 생물정신의학
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• 제24권1호
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• pp.1-9
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• 2017

The proton magnetic resonance spectroscopy ($^1H-MRS$) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.1-9
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• 2013

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

• Journal of Microbiology and Biotechnology
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• 제27권5호
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• pp.939-942
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• 2017

The cellular composition and metabolic compounds of Leuconostoc mesenteroides ATCC 8293 were analyzed after cultivation in an anaerobic chemostat. The macromolecular composition was 24.4% polysaccharide, 29.7% protein, 7.9% lipid, 2.9% DNA, and 7.4% RNA. Its amino acid composition included large amounts of lysine, glutamic acid, alanine, and leucine. Elements were in the order of C > O > N > H > S. The metabolites in chemostat culture were lactic acid (73.34 mM), acetic acid (7.69 mM), and mannitol (9.93 mM). These data provide a first view of the cellular composition of L. mesenteroides for use in metabolic flux analysis.

• 한국의학물리학회지:의학물리
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• 제12권1호
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• pp.31-39
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• 2001

핵자기공명분광학(NMR Spectroscopy)을 이용해서 우리는 생물체의 조직안에 있는 각종 대사물질들을 측정할 수 있게 되었으며, 이것은 또 지금까지 알려진 여러 방법 중에서 생물체내의 신진대사 물질이나 생화학적인 변화를 비침습적(noninvasive)으로 알아낼 수 있는 유일한 방법에 속한다. 양성자 핵자기공명분광학은 최근들어 사람이나 흑은 동물뇌의 생화학적인 특성을 연구하는데 많이 사용되어오고 있다. 핵자기공명영상은 주로 물분자에 있는 양성자의 밀도와 그들의 이완현상(relaxation phenomena)을 측정하여 영상화하지만 핵자기공명분광학은 생체조직내의 신진대사에 관한 생화학적인 정보를 제공한다. 많은 경우에 있어서 핵자기공명분광학은 CT나 MRI 영상에서는 발견할 수 없는 정보를 제공함으로써 특정질병의 진단에 사용될 수 있으며, 따라서 환자들의 질병상태를 효과적으로 진단하는데 쓰여질 수 있다. 따라서 본 연구에서는 사람의 뇌에서 수소 핵자기공명분광학을 이용하여 대사물질들의 농도를 정량화하는 방법을 시도하였다. 이를 위해 펀텀을 이용하여 대사물질들 각각의 스팩트럼을 구했고, 성인 남녀 16명을 대상으로 insula gray matter 부위의 대사물질들의 농도를 측정하였다. 그리고 이 값들은 다른 연구자들에 의해 밝혀진 값들과 매우 근사한 값을 제공하였다.