• Journal of Microbiology and Biotechnology
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• 제11권6호
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• pp.946-950
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• 2001

Slow-growing pathogenic mycobacterium species, including Mycobacterium bovis BCG, secrete a large amount of glutamine synthetase into culture media. Extracellular and intracellular glutamine synthetases were purified from M. bovis BCG. While the native molecular weights of both glutamine synthetases were estimated to be 370.2 kDa, those of the subunits were 61.7 kDa, indicating that the native forms were composed of 6 subunits. The enzymes showed a hhigh thermal stability and high degree of sequence similarity with the glutamine synthetase from M. tuberculosis in the N-terminal amino acid sequence. Western blotting analysis indicated that the antibodies prepared against both the extracellular and intracellular enzymes exhibited common antigen determinants.

• Biomolecules & Therapeutics
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• 제26권1호
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• pp.19-28
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• 2018

Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling. Furthermore, we summarize the potential therapeutic approaches of targeting glutamine metabolism for the treatment of numerous types of cancer.

• Nutritional Sciences
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• 제6권4호
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• pp.189-194
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• 2003

Most of the ethyl alcohol consumed by humans is oxidized to acetaldehyde in the liver by the cytoplasmic alcohol dehydrogenase (ADH) system. For this ADH-catalyzed oxidation of alcohol, $NAD^+$ is required as the coenzyme and $NAD^+$becomes reduced to NADH. As the $NAD^+$becomes depleted and NADH accumulates, alcohol oxidation is reduced. For continued alcohol oxidation, the accumulated NADH must be quickly reoxidized to $NAD^+$, and it is this reoxidation of NADH to $NAD^+$that is known to be the rate-limiting step in the overall oxidation rate of alcohol The reoxidation of NADH to $NAD^+$is catalyzed by lactate dehydrogenase in the cytoplasm of hepatocytes, with pyruvate being utilized as the substrate. The pyruvate may be supplied from alanine as a result of amino acid metabolism via the urea cycle. Also, glutamine is thought to help with the supply of pyruvate indirectly, and to activate the urea cycle by producing $NH_3$. Thus, in the present study, we have examined the effects of alanine and glutamine on the alcohol oxidation rate. We utilized isolated perfused liver tissue in a system where media containing alanine and glutamine was circulated. Our results showed that when alanine (5.0mM) was added to the glucose-free infusion media, the alcohol oxidation rate was increased by 130%. Furthermore, when both glutamine and alanine were added together to the infusion media, the alcohol oxidation rate increased by as much as 190%, and the rate of urea nitrogen production increased by up to 200%. The addition of glutamine (5.0mM) alone to the infusion media did not accelerate the alcohol oxidation rate. The increases in the rates of alcohol oxidation and urea nitrogen production through the addition of alanine and glutamine indicate that these amino acids have contributed to the enhanced supply of pyruvate through the urea cycle. Based on these results, it is concluded that the dietary supplementation of alanine and glutamine could contribute to increased alcohol detoxification through the urea cycle, by enhancing the supply of pyruvate and $NAD^+$to ensure accelerated rates of alcohol oxidation.

• Asian-Australasian Journal of Animal Sciences
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• 제16권8호
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• pp.1182-1187
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• 2003

Two experiments involving 92 crossbred, 21 day old weaned pigs were used to evaluate the effect of glutamine supplement in a dietary or culture medium on lymphocyte proliferation. In Exp. 1, 88 pigs were fed diets supplemented with 0, 0.5, 1.0, or 1.5% glutamine for 28 days. Lymphocytes were prepared from peripheral blood mononuclear cells (PBMC), ileal Peyer's patches (PP), the mesenteric lymph node (MLN), and the spleen in each dietary supplement group on days 7, 14, or 28 postweaning. Lymphocytes were cultured at $37^{\circ}C$ for 72 h in a RPMI-1640 medium with or without mitogen-stimulated, and pulsed with 3Hthymidine for an additional 18 h. The stimulation index of PBMC proliferation in 1.0% dietary glutamine supplement group and both of the MLN and splenocytes proliferation in 1.5% dietary glutamine supplement group was significantly (p<0.05) increased at 14 days postweaning. In Exp. 2, four weaned pigs were fed a basal diet for 14 days. The 3H-thymidine incorporation of PBMC, PP, and MLN cells, incubated with 0.125 to 0.25 mM glutamine in culture medium were markedly enhanced with Con A-stimulated, however, the splenocyte proliferation was not affected in the addition of glutamine medium. These observations suggest that dietary glutamine supplement might enhance the lymphocyte proliferation of weaned pigs.

• 약학회지
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• 제51권1호
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• pp.1-6
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• 2007

The aim of this study was to examine whether administration of glutamine are able to prevent the methotrexate induced gut barrier damage, bacterial translocation, and weight changes. The animals with glutamine were fed with L-glutamine (1.2 and 2.4 mg/kg/day) for 7 days before methotrexate administration (20 mg/kg orally). 48 hour after methotrexate administration, intestinal permeability were measured for an assessment of the gut barrier dysfunction. Also, enteric aerobic bacterial counts, number of gram-negatives in mesenteric lymph node (MLN), liver spleen, kidney and heart were measured for an assessment of the enteric bacterial number and bacterial translocation. Amounts of food intake, body weight changes and organ weight changes of liver spleen, kidney and heart were measured. Methotrexate administration caused body and liver weight loss regardless amounts of food intakes. Methotrexate induced increasing intestinal permeability, enteric bacterial undergrowth and bacterial translocation to MLN, liver and spleen, but not kidney and heart. The supplements with glutamine reduced the intestinal permeability bacterial translocation, and not influences enteric bacterial number, and body and liver weight changes. This study suggested that glutamine might effectively reduce methotrexate induced intestinal damage and bacterial translocation, but not influence body and organ weight loss.

• 한국식품영양과학회지
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• 제42권8호
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• pp.1167-1174
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• 2013

암세포를 포함한 생체 내 빠른 분열을 요구하는 세포 집단에서 세포 내 구성요소 및 에너지원으로서 글루타민의 요구량이 증대되지만, 종양세포의 글루타민 의존적 대사작용에 관한 기전은 여전히 잘 알려진 바 없다. 본 연구에서는 LnCaP 전립선 암세포의 이동성 및 침윤성에 미치는 글루타민 결핍효능을 조사하였다. 본 연구의 결과에 의하면 LnCaP 세포에서 글루타민 결핍에 의하여 세포의 이동성 및 세포의 침윤성이 현저하게 억제되었으며, 이러한 이동성 및 침윤성 억제는 TIMPs의 발현 증대에 의한 MMPs의 발현 감소 및 그들의 효소적 활성 저하와 연관성이 있었다. 또한 글루타민이 결핍된 조건에서 배양된 LnCaP 세포에서 TER의 현저한 증가가 관찰되었는데, 이는 TJs의 조절인자인 claudin family 발현의 차단에 의한 것으로 생각되어진다. 본 연구의 결과에 의하면 암세포의 증식에서 글루타민의 결핍은 TJ의 결합력 증대와 MMPs의 활성을 저하시킴으로써 암세포 전이에 가장 기본적인 과정인 암세포의 이동성과 침윤성을 억제시킬 수 있을 것으로 생각된다.

• 생명과학회지
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• 제23권7호
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• pp.926-932
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• 2013

글루타민과 혈청은 세포의 생존과 증식에 기본적으로 요구되지만, 그들의 양적 변화에 따른 내피세포 반응에 관한 신호전달 관련 연구는 거의 이루어지지 않았다. 본 연구에서는 인체 재대정맥 내피세포(human umbilical vein endothelial cells, HUVECs)의 증식에 미치는 글루타민과 혈청의 결핍에 관한 영향을 조사하였다. 본 연구의 결과에 의하면 글루타민 및 혈청이 결핍된 조건에서 배양된 HUVECs의 증식 억제는 apoptosis 유발과 연관성이 있었음을 DAPI staining에 의한 핵의 형태 변화와 유세포 분석을 통하여 확인하였다. 비록 혈청이 결핍된 조건보다 글루타민 결핍에 의한 apoptosis 유발 정도가 더 높게 나타났으나, 두 현상에 의한 apoptosis의 유발은 anti-apoptotic Bcl-2 및 Bcl-xL의 발현 저하와 pro-apoptotic Bax의 발현 증가, IAP family 단백질의 발현 감소, caspase의 활성 증가에 따른 PARP 단백질의 단편화와 연관성이 있었다. 또한 이러한 조건에서 HUVECs의 Bid 발현의 감소 또는 tBid 발현의 증가 현상이 관찰되어, 글루타민 또는 혈청 결핍에 의한 HUVECs의 apoptosis 유발은 세포막 수용체 및 미토콘드리아 활성 경로를 동시에 통하여 이루어지고 있음을 알 수 있었다. 그러나 글루타민과 혈청이 동시에 결핍된 조건에서 배양된 HUVECs의 증식 억제 현상은 각각의 조건에 비하여 증가되었으나 apoptosis는 유발되지 않았다.

• 생명과학회지
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• 제23권6호
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• pp.832-837
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• 2013

본 연구에서는 생체 내 구성요소 및 에너지원으로서 중요한 역할을 하는 글루타민 결핍에 의한 인체 전립선 PC3 암세포의 증식에 관한 기전 연구를 실시하였다. 글루타민 결핍에 의한 PC3 세포의 증식억제는 세포주기 G2/M arrest와 연관성이 있었으나, apoptosis 유발 현상은 관찰되지 않았다. 글루타민 결핍에 의한 G2/M arrest는 전사 및 번역 수준에서 Cdc2, cyclin A 및 cyclin B1의 발현 억제 및 p53 비의존적인 p21(WAF1/CIP1)의 발현 증가와 연관성이 있었다. 아울러 글루타민 결핍은 Chk1 및 Chk2의 인산화를 증가시켰으나, Cdc25C의 인산화는 감소시켰다. 본 연구의 결과는 글루타민 결핍에 의한 PC3 세포의 증식억제가 apoptosis 유발과는 상관없이 G2/M arrest를 유발시킨다는 첫 번째 증거이다.

• 대한화학회지
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• 제38권3호
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• pp.200-207
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• 1994

Wistar계 쥐의 신장 조직을 암모니아 기체 감응전극에 고정화하여 조직센서를 제작하고, L-glutamine을 정량하기 위한 최적 조건을 조사하였다. 그 결과, $30^{\circ}C$, pH 7.8의 0.05M 인산완충용액과 30 ${\mu}m$ 두께의 신장을 사용하였을 경우, 정량 가능한 직선범위는$ 8.0{\times}10^{-5}{\sim}1.0{\times}10^{-2} M$이었으며, 감응도는 53.8 mV/decade로 나타났고, 감응시간은 3~5분 소요되었다. 또한 같은 최적 조건하에서 조직을 파쇄하여 얻은 세포소기관을 전극에 고정화시킨 센서의 경우, 정량 가능한 직선범위는 $1.2{\times}10^{-4}{\sim}5.0{\times}10^{-3} M$이었으며, 감응도는 54.0 mV/decade, 감응시간은 6~7분이 소요되었다. 이와 같이 본 연구에서는 쥐의 신장 조직 및 세포 소기관을 이용하여 L-glutamine을 정량 분석할 수 있는 조직센서 개발에 관하여 연구하였다.

• 미생물학회지
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• 제29권2호
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• pp.97-103
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• 1991

Glutamine phosphoribosylpyrophosphate amidotransferase of Streptomyces tubercidicus was purified and characterized. Molecular weight of the isolated enzyme was determined to be approximately 230,000 and was composed foru identical subunits having a molecular weight of 58,000. This enzyme was strongly inhibited by AMP while considerably inhibited by ATP and GTP. Inhibition effect of enzyme activity by AMP was antagonized by increased concentration of substrate, PRPP, and metal ion (especially, $Mg^{++}$) was essential in both catalytic activity and nucleotide inhibition of this enzyme. Therefore, it was confirmed that end product inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by adenine participated in the regulation of tubercidin biosynthesis from Streptomyces tubercidicus.s.