• 제목/요약/키워드: cholesterol biosynthesis

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혈청 콜레스테롤과 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (Serum Cholesterol and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase)

  • 최용순;이상영
    • 한국식품영양과학회지
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    • 제21권5호
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    • pp.580-593
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    • 1992
  • Cholesterol have many essential functions as a component of cellular and subcellular membranes, metabolic precursor of bile acids and steroid hormones, and obligatory part of the metabolic systems involved in DNA synthesis and cell division. These essential funtions demand a continuous and appropriate supply of cholesterol to the tissues. Body cholesterol pool is maintained by the balance of acquirement from diets, de novo synthesis, and excretion either as bile acids or neutral steroids. In these metabolic process, cholesterol biosynthesis is controlled by the change in the activity of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase. Under most physiological or nutritional situations, the activity of this enzyme is adroitly regulated to maintain tissue cholesterol balance. Excess cholesterol accumulation in the cells induces the decrease in the number of LDL-receptor, followed by the increase in the level of serum LDL-cholesterol. Increase in the level of serum cholesterol appears to be an important determinant for the incidence of the coronary heart disease. Dietary intervention may be helpful in alleviating an increase in the level of serum cholesterol or body cholesterol pool.

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Soluble isocitrate dehydrogenase plays a key role in obesity and hyperlipidemia

  • Koh, Ho-Jin;Lee, Su-Min;Huh, Tae-Lin
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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    • pp.5-7
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    • 2003
  • NADPH is an essential co-factor for fat and cholesterol biosynthesis. However, the role of cytosolic NADP$\^$+/-dependent isocitrate dehydrogenase (IDPc), a putative NADPH producer, in the control of the fat and cholesterol metabolism has not been assessed. Here we report that increased or decreased IDPc expression in 3T3-Ll fat cells promoted or retarded adipogenesis, respectively. Furthermore, overexpression of IDPc in transgenic mice exhibited fatty liver, hypertriglyceridemia, hypercholesterolemia and obesity by increasing NADPH production leading to subsequent stimulation of acetyl-coenzyme A and malonyl-coenzyme A consumption. In contrast, administrations of a synthetic IDPc inhibitor, DAl1004, to ob/ob mice effectively reduced body weight with lowering cholesterol and triglyceride levels. In addition, a positive relationship (${\gamma}$ = 0.69, $\rho$<0.0l) between plasma IDPc activity and body mass indexes was observed in 98 randomly-selected human volunteers. Our findings strongly indicate that NADPH produced by IDPc plays an important role in controlling body fat and lipid biosynthesis.

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대두 이소플라본 당전이 반응 산물의 콜레스테롤 생합성 저해 효과 (Inhibitory Effects of Transglycoslyation Products of Soy Isoflavones on Cholesterol Biosynthesis)

  • 유랑국;최승준;문태화;심재훈
    • 한국식품영양과학회지
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    • 제45권2호
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    • pp.293-297
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    • 2016
  • HMG-CoA reductase는 체내 콜레스테롤 생합성에 있어서 속도제한단계(율속) 효소이다. 본 연구는 HMG-CoA reductase에 대한 이소플라본 배당체의 저해 효과를 연구하였다. $100{\mu}M$의 농도에서 genistein-7-O-triglucoside(G2-genistin)는 HMG-CoA reductase 활성을 약 18% 정도 저해하였으나, daidzein-7-O-triglucoside는 저해 효과를 갖지 않았다. 시리아햄스터 HMG-CoA reductase의 반응속도 실험에서 G2-genistin은 농도에 관계없이 $V_{max}$의 저해 정도가 일정하였으며, 이것은 G2-genistin이 HMG-CoA reductase의 경쟁적 저해제로 작용함을 시사하고 HMG-CoA reductase의 활성을 직접적으로 저해함으로써 혈중 콜레스테롤 함량을 감소시킬 수 있음을 예상할 수 있다.

Glycyrrhizin의 Hypocholesteroleinic Action에 관(關)한 연구(硏究) (Studies on the Hypocholesterolemic Activities of Glycyrrhizin)

  • 김창환
    • 대한약리학회지
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    • 제1권1호
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    • pp.7-16
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    • 1965
  • Glycyrrhizin, an active constituent of Glycyrrhiza, was chemically extracted and its hypocholesterolemic activities were studied in rats. Following were the results: 1. The Sprague Dowley rats fed with the standard diet were divided into 4 groups, $50{\sim}60$ in each, and glycyrrhizin was given in doses of 0 (control), 0.5, 1.0 and 2.0mg per 100gm body weight daily for 10, 20, 30, and 60 days. Glycyrrhizin showed more or less the hypocholesterolemic activities in all animals. All of the animal groups to which 1. 0mg and 2.0mg of glycyrrhizin were given died before 60 days, while no mortality cases was noted in the group to which 0.5mg of glycyrrhizin was given. 2. Cholesterol administration induced hypercholesterolemia in all experimental animals, however, simultaneous administration of cholesterol with 0.5mg of glycyrrhizin suppressed the rise of the total serum cholesterol levels. The former group did not survive until 56 days, while the latter did. 3. Glycyrrhizin also Suppressed the cholesterol biosynthesis and incorporation of cholesterol in the liver tissues. 4. Glycyrrhizin induced the increase of the fecal excretion of the sterol compounds.

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거피 탈지 콩가루 식이가 흰쥐의 콜레스테롤 대사와 소화생리에 미치는 영향 (Effects of Dehulled Defatted Soy Flour on Cholesterol Metabolism and Gastronitestinal Physiology in Rats)

  • 송영성
    • Journal of Nutrition and Health
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    • 제33권4호
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    • pp.395-402
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    • 2000
  • This study was carried out to explore the hypocholesterolemic effect of dehyulled defatty soy flour and its possible mechanisms including endocrine status, cholesterol biosynthesis, and fecal excretion in rats. Animals fed casein were used as control and each phospholipid compared with casein feeding. Cholesterol concentrations in all lipoprotein fraction were significantly lower in defatted soy flour group compared with casein-fed control. Defatted soy flour feeding also significantly lowered hepatic total lipid, cholesteol and TG, and increaed fecal bile acid excretion by 270% compared with casein feeding. Defattd soy flour feeding had no significant effect on plasma thyroid hormone levels and hepatic 3-hydroxy-3-methyl glutary coenzyme A(HMG-CoA) reductase activity. However, plasma T4 concentration was slightly elevated and HMG-CoA reductase activity was suppressed in defatted soy flour group. These metabolic alterations partially explain the reduced plasma and hepatic cholesterol levels of rats fed defatted soy flour.

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인삼사포닌의 저밀도지질단백질(LDL)수용체에 미치는 영향 (Effect of Ginseng Saponin on LDL Receptor Biosynthesis)

  • 주충노;이희봉;이용우;강인철
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1988년도 학술대회지
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    • pp.47-54
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    • 1988
  • 세포막의 주요 구성성분인 콜레스테롤은 고등생명체의 성장 및 생존에 필수적인 물질이다. 그러나 혈중 콜레스테롤의 농도가 너무 높으면 동맥경화증을 유발하여 매우 치명적이다. 본 연구는 고려인삼(Panax ginseng C.A. Meyer) 뿌리의 주요성분의 하나인 사포닌류의 고콜레스테롤 혈중 억제효과를 규명하기 위해 시도되었다. 고콜레스테롤 식이를 인삼사포닌과 함께 또는 단독으로 투여한 토끼나 쥐에 $^{125}I-LDL$을 주입한 후 혈액으로부터 $^{125}I-LDL$의 제거속도를 추적한 결과 고콜레스테롤 식이만을 투여한 대조군보다 인삼사포닌을 함께 투여한 시험군이 $^{125}I-LDL$의 제거속도가 훨씬 빨랐다. 고콜레스테롤식이를 투여한 쥐의 LDL수용체 생합성에 미치는 ginsenoside 혼합물과 정제된 ginsenoside $Rb_{1},\;Rb_{2},\;Re,\;Rg_{1}$의 영향을 조사하였다. 쥐 간의 LDL 수용체 수준을 분석한 결과 시험군이 대조군에 비해 크게 높았으며 다른 장기(신장, 정소, 부신피질)의 경우에도 간에서의 결과와 유사하였다. 또한 간파쇄액을 효소원으로 사용하여 콜레스테롤 부터의 담즙산 합성에 미치는 ginsenoside의 영향을 시험관내에서 관찰한 결과 반응 혼합물에서의 ginsenoside의 농도가 $(10^{-3}-10^{-4}\%)$일 때 담즙산합성이 현저히 증가되었다. 위와 같은 실험결과로 미루어 보아 ginsenoside는 세포 내부에서의 콜레스테롤 대사를 촉진하여 세포내의 콜레스테롤 농도를 저하시킴으로써 콜레스테롤의 LDL 수용체 합성 억제를 완화시켜주는 것이라고 생각된다.성분들은 cyclooxygenase에 직접 작용하지 않는다는 것을 설명해 준다. 2. Panaxadiol (500 ${\mu}g/ml$$PGE_{2}$ 생성에는 영향이 없으나 $PGF_{2}{\alpha}$생성에 유의적인 차이를 보이지 않으나 농도의존적으로 $TxB_{2}$의 생성을 감소시켰고 6-keto-$PGF_{1}{\alpha}$의 생성을 증가시켰는데 이는 $TxA_{2}$ synthetase 억제제인 imidazole의 효과와 유사하였다. 4. G-Re는 $1{\times}10^{-5}g/ml$ 이하의 농도에서는 효과가 없으나 $1{\times}10^{-4}g/ml$ 이상의 농도에서 농도의존적으로 유의성 있는 $PGE_{2},\;PGF_{2}{\alpha},\;TXB_{2}$의 생성억제와 함께 6-keto-$PGF_{1}{\alpha}$ 증가를 보였다. 이는 prostacyclin synthetase를 자극하는 serotonin의 효과와 같은 작용으로서 prostacyclin synthetase 억제제인 tranylcypromine에 대하여 길항효과를 보였다. 5. $TxB_{2}$생성억제 작용을 나타내는 ginsenoside들의 효과를 뒷받침하기 위하여 인삼 saponin 성분을 전처치한 patelet rich plasma에서 혈소판 응집시험 결과, ADP로 유도된 혈소판 응집반응에는 모든 인삼 saponin 성분들이 효과가 없었으나 arachidonic acid로 유도된 혈소판 응집반응에는 $G

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Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet

  • Kim, Min-Ji;Kim, Yang-Ha
    • Nutrition Research and Practice
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    • 제4권3호
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    • pp.191-195
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    • 2010
  • There is an increasing interest in curcumin (Curcuma longa L.) as a cardiovascular disease (CVD) protective agent via decreased blood total cholesterol and low-density lipoprotein-cholesterol (LDL-cholesterol) level. The aim of this study was to investigate further the potential mechanism in the hypocholesterolemic effect of curcumin by measuring cholesterol 7a-hydroxylase (CYP7A1), a rate limiting enzyme in the biosynthesis of bile acid from cholesterol, at the mRNA level. Male Sprague-Dawley rats were fed a 45% high fat diet or same diet supplemented with curcumin (0.1% wt/wt) for 8 weeks. The curcumin diet significantly decreased serum triglyceride (TG) by 27%, total cholesterol (TC) by 33.8%, and LDL-cholesterol by 56%, respectively as compared to control group. The curcumin-supplemented diet also significantly lowered the atherogenic index (AI) by 48% as compared to control group. Hepatic TG level was significantly reduced by 41% in rats fed with curcumin-supplemented diet in comparison with control group (P < 0.05). Conversely, the curcumin diet significantly increased fecal TG and TC. The curcumin diet up-regulated hepatic CYP7A1 mRNA level by 2.16-fold, compared to control group p (P < 0.05). These findings suggested that the increases in the CYP7A1 gene expression may partially account for the hypocholesterolemic effect of curcumin.

시험관법에의한 식물열수추출물의 3-Hydroxy-3-Methylglutaryl CoA Reductase 및 Acyl-CoA:Cholesterol Acyltransferase 활성 저해도 측정 (Measurement of Inhibitory Activities on 3-Hydorxy-3-Methylglutaryl CoA Reductase and Acyl-CoA:Cholesterol Acyltransferase by Various Plant Extracts in vitro)

  • 최명숙;이희자
    • 한국식품영양과학회지
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    • 제28권4호
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    • pp.958-962
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    • 1999
  • Hydroxy methylglutaryl CoA(HMG CoA) reductase and acyl CoA:cholesterol acyltransferase(ACAT) are two important enzymes that are associated with regulation of cholesterol metabolism. The inhibitors of HMG CoA reductase and ACAT are very effective in lowering serum cholesterol in most animal species. In present study, various plant extracts with hot water were used to examine the inhibitory activities against HMG CoA reductase and ACAT that are involved in cholesterol biosynthesis and cholesterol esterification in tissues, respectively. The extracts of Fagophyrum rotundatum, Rosa multiflora, Rosa rugosa and Alisma orientalis exhibited significant inhibitory activities against the ACAT, 29%, 24%, 19%, and 18%, respectively. However the extracts of Typha augustifolia, Polygonum cuspidatum, Crataegus pinnatifida, Polygonum multiflorum inhibited the HMG CoA reductase activity by 53%, 42%, 37%, and 33% respectively. Results suggest that these plant extracts might play important roles in the regulation of the cholesterol metabolism in vivo.

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Improvement of Natamycin Production by Cholesterol Oxidase Overexpression in Streptomyces gilvosporeus

  • Wang, Miao;Wang, Shaohua;Zong, Gongli;Hou, Zhongwen;Liu, Fei;Liao, D. Joshua;Zhu, Xiqiang
    • Journal of Microbiology and Biotechnology
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    • 제26권2호
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    • pp.241-247
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    • 2016
  • Natamycin is a widely used antifungal antibiotic. For natamycin biosynthesis, the gene pimE encodes cholesterol oxidase, which acts as a signalling protein. To confirm the positive effect of the gene pimE on natamycin biosynthesis, an additional copy of the gene pimE was inserted into the genome of Streptomyces gilvosporeus 712 under the control of the ermE* promoter (permE*) using intergeneric conjugation. Overexpression of the target protein engendered 72% and 81% increases in the natamycin production and cell productivity, respectively, compared with the control strain. Further improvement in the antibiotic production was achieved in a 1 L fermenter to 7.0 g/l, which was a 153% improvement after 120 h cultivation. Exconjugants highly expressing pimE and pimM were constructed to investigate the effects of both genes on the increase of natamycin production. However, the co-effect of pimE and pimM did not enhance the antibiotic production obviously, compared with the exconjugants highly expressing pimE only. These results suggest not only a new application of cholesterol oxidase but also a useful strategy to genetically engineer natamycin production.