• Title/Summary/Keyword: C metabolism

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Inhibition of GM3 Synthase Attenuates Neuropathology of Niemann-Pick Disease Type C by Affecting Sphingolipid Metabolism

  • Lee, Hyun;Lee, Jong Kil;Bae, Yong Chul;Yang, Song Hyun;Okino, Nozomu;Schuchman, Edward H.;Yamashita, Tadashi;Bae, Jae-Sung;Jin, Hee Kyung
    • Molecules and Cells
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    • v.37 no.2
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    • pp.161-171
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    • 2014
  • In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NP-C mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy.

FUNGAL EXTRACELLULAR POLYSACCHARIDES INVOLVED IN RECYCLING OF METABOLITES AND OSMOTOLERANCE OF PENICILLIUM FELLUTANUM : APPLICATION OF $^{13}$ C-NMR SPECTROSCOPY FOR THE STUDY ON FUNGAL PHYSIOLOGY AND METABOLISM

  • Park, Yong-Il;Gander, John.-E.
    • 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.

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Correlation between Serum Osteocalcin and Hemoglobin A1c in Gwangju General Hospital Patients (광주 소재 한 종합병원을 방문한 성인에서 혈중 Osteocalcin과 HbA1c의 상관관계)

  • Seo, Yo-Han;Shin, Hee-Young
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.3
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    • pp.313-319
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    • 2018
  • Recently, there have been many studies on the relationship between the bone metabolism and the mechanism of diabetes. In those studies, it was shown that osteocalcin can be involved in the treatment of type 2 diabetes. Therefore, this study examined the correlation between osteocalcin and HbA1c. From January 1, 2015 to December 31, 2016, a total of 714 adults aged 40 years or older ($70.8{\pm}10.4years$, 452 males), in whom both osteocalcin and HbA1c checked in a general hospital in Gwangju, were enrolled in the study. The serum calcium, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, and 25-(OH) vitamin D were measured and basic information, such as the height and weight, were recorded. There was a weak negative correlation (r=-0.183, P<0.001) between the osteocalcin and HbA1c levels in diabetic patients but a negative correlation (r=-0.251, P<0.001) when adjusted by all other study variables. The present study showed that there was a negative correlation between the osteocalcin and HbA1c levels in diabetic patients. The relationship between the bone metabolism and the incidence of diabetes mellitus should be studied based on the influence of biological mechanisms and associated factors of bone and glucose metabolism.

Effects of Cheonggukjang Diet and Aerobic Exercise on Lipid Metabolism and Antioxidant Enzyme in Rats (청국장 식이와 유산소 운동이 흰쥐의 지질대사 및 항산화효소에 미치는 영향)

  • Kim, Sang-Woo;Jeong, Seon-Tea;Baek, Yeong-Ho
    • Journal of Life Science
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    • v.23 no.5
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    • pp.657-663
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    • 2013
  • The purpose of this study was to examine the effects of a cheonggukjang diet and aerobic exercise on lipid metabolism and antioxidant enzyme activity in rats. Thirty-two Sprague Dawley rats were randomized into a cheonggukjang diet with aerobic exercise (A), aerobic exercise (B), cheonggukjang diet (C), and control group (D). The cheonggukjang diet group consumed 20 g of 20% cheonggukjang a day with their normal diet. Exercise training consisted of treadmill running (25~40 min, 5 day/wk) and the exercise intensity was gradually increased. The results are as follows: T-C was significantly lower (p<0.05) in A compared to B and C. TG was significantly lower (p<0.001) in A compared to D. B and C were significantly lower than D. HDL-C was significantly higher (p<0.05) in C compared to D. LDL-C was not statistically different across the groups. Additionally, TBARS were not statistically different in the control or experimental groups. SOD was significantly lower (p<0.05) in A compared to D. C was significantly lower (p<0.05) that of D. CAT and GPx failed to reach the statistical difference between experimental and control groups. The major findings of this study were that aerobic exercise with a chenggukjang diet intervention improved lipid profiles and antioxidant capacity in this animal model. Therefore, a cheonggukjang diet and aerobic exercise will help to improve antioxidant capacity and prevent lifestyle related diseases.

C-Glycoside-Metabolizing Human Gut Bacterium, Dorea sp. MRG-IFC3

  • Huynh Thi Ngoc Mi;Santipap Chaiyasarn;Heji Kim;Jaehong Han
    • Journal of Microbiology and Biotechnology
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    • v.33 no.12
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    • pp.1606-1614
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    • 2023
  • Biochemical gut metabolism of dietary bioactive compounds is of great significance in elucidating health-related issues at the molecular level. In this study, a human gut bacterium cleaving C-C glycosidic bond was screened from puerarin conversion to daidzein, and a new, gram-positive C-glycoside-deglycosylating strain, Dorea sp. MRG-IFC3, was isolated from human fecal sample under anaerobic conditions. Though MRG-IFC3 biotransformed isoflavone C-glycoside, it could not metabolize other C-glycosides, such as vitexin, bergenin, and aloin. As evident from the production of the corresponding aglycons from various 7-O-glucosides, MRG-IFC3 strain also showed 7-O-glycoside cleavage activity; however, flavone 3-O-glucoside icariside II was not metabolized. In addition, for mechanism study, C-glycosyl bond cleavage of puerarin by MRG-IFC3 strain was performed in D2O GAM medium. The complete deuterium enrichment on C-8 position of daidzein was confirmed by 1H NMR spectroscopy, and the result clearly proved for the first time that daidzein is produced from puerarin. Two possible reaction intermediates, the quinoids and 8-dehydrodaidzein anion, were proposed for the production of daidzein-8d. These results will provide the basis for the mechanism study of stable C-glycosidic bond cleavage at the molecular level.