• 제목/요약/키워드: cholesterol biosynthesis

검색결과 100건 처리시간 0.022초

A Gene Cluster for the Biosynthesis of Dibenzodioxocinons in the Endophyte Pestalotiopsis microspora, a Taxol Producer

  • Liu, Yanjie;Chen, Longfei;Xie, Qiaohong;Yu, Xi;Duan, Anqing;Lin, Yamin;Xiang, Biyun;Hao, Xiaoran;Chen, Wanwan;Zhu, Xudong
    • Journal of Microbiology and Biotechnology
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    • 제29권10호
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    • pp.1570-1579
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    • 2019
  • The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in $g{\alpha}1{\Delta}$, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.

Biochemical Characterization of Recombinant UDP-Glucose:Sterol 3-O-Glycosyltransferase from Micromonospora rhodorangea ATCC 31603 and Enzymatic Biosynthesis of Sterol-3-O-β-Glucosides

  • Hoang, Nguyen Huu;Hong, Sung-Yong;Huong, Nguyen Lan;Park, Je Won
    • Journal of Microbiology and Biotechnology
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    • 제26권3호
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    • pp.477-482
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    • 2016
  • A uridine diphosphate-glucose:sterol glycosyltransferase-encoding gene was isolated and cloned from the established fosmid library of Micromonospora rhodorangea ATCC 27932 that usually produces the aminoglycoside antibiotic geneticin. The gene consists of 1,185 base pairs and encodes a 41.4 kDa protein, which was heterologously expressed in Escherichia coli BL21(DE3). In silico analyses of the deduced gene product suggested that it is a member of the family 1 glycosyltransferases. The recombinant protein MrSGT was able to catalyze the transfer of a glucosyl moiety onto the C-3 hydroxy function in sterols (β-sitosterol, campesterol, and cholesterol), resulting in the corresponding steryl glucosides (β-sitosterol-3-O-β-ᴅ-glucoside, campesterol-3-O-β-ᴅ-glucoside, and cholesterol-3-O-β-ᴅ-glucoside). This enzyme prefers phytosterols to cholesterol, and also shows substrate flexibility to some extent, in that it could recognize a number of acceptor substrates.

The Juhwangjam (JH) 3rd day of fifth instar silkworm exhibits antioxidative properties and prevents high-fat diet-induced hypercholesterolemia

  • Ji Hae, Lee;Yeon-Ji, Kim;Kyungho, Kim;Hyun Bok, Kim;HaeYong, Kweon
    • International Journal of Industrial Entomology and Biomaterials
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    • 제45권2호
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    • pp.126-130
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    • 2022
  • The silkworm is a food material that can simultaneously ingest phytochemicals from mulberry leaves, proteins with essential amino acids, and fatty acids. They are known to have hypoglycemic properties; however, further functional investigation is needed. In this study, four varieties of 3rd day of fifth instar silkworm with different cocoon colors, namely Baegokjam (BG), Goldensilk (GS), Yeonnokjam (YN), and Juhwangjam (JH), were compared in terms of antioxidant properties and cholesterol-lowering effect. JH, which had the highest polyphenol content (+38% vs. GS, p<0.05) showed high antioxidant efficacy. Treatment with JH also resulted in the lowest cholesterol biosynthesis enzyme activity (28% vs. control, p<0.05). In the animal study, high-fat diet (HFD)-fed mice that were orally administered JH extract for 12 weeks showed lower body weight gain (-10.4% vs. HFD, p<0.05) and serum total cholesterol levels (-12.7% vs. HFD, p<0.05). Comparing the varieties, JH had the highest effect. In future studies, analysis of the active ingredients according to their variety should be done.

Aspergillus terreus의 발효조건이 lovastatin 생산에 미치는 영향 (Effect of Fermentation Conditions on the Production of Lovastatin by Aspergillus terreus)

  • 김병곤;전계택;정용섭
    • KSBB Journal
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    • 제15권5호
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    • pp.507-513
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    • 2000
  • 고지혈증 치료제인 lovastatin을 Aspergillus terreus로부터 생산하기 위해 발효조 배양설험에서 교반속도와 pH에 대한 영향올 조사하였다. 최적 교반속도는 400 rpm이었고 pH는 5.8로 유지하였을 때 lovastatin 생산이 최대였으며, 교반속도 보다 pH가 lovastatin 생산에 더 많은 영향을 미치는 것으로 나타났다 L-tryptop뼈n과 L-histi빼le의 첨가시기에 따른 lovastatin 생산량을 실험한 결과, 둘다 발효초기부터 첨가하여 배양하 는 것이 효과적이었다 L-tryptophan을 발효초기에 첨가한 최 적배지와 최적 환경조건인 교반속도 400 rpm, pH 5.8에서 회 분식 배양을 수행한 결과 기본배지를 이용하여 실험한 배양 결과보다 약 10배 정도 많은 836 mg/L이었고, 생산성은 3.5 mg/L.hr였다

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ATHEROSCLEROSIS, CHOLESTEROL AND EGG - REVIEW -

  • Paik, I.K.;Blair, R.
    • Asian-Australasian Journal of Animal Sciences
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    • 제9권1호
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    • pp.1-25
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    • 1996
  • The pathogenesis of atherosclerosis can not be summarized as a single process. Lipid infiltration hypothesis and endothelial injury hypothesis have been proposed and investigated. Recent developments show that there are many points of potential interactions between them and that they can actually be regarded as two phases of a single, unifying hypothesis. Among the many risk factors of atherosclerosis, plasma homocysteine and lipoprotein(a) draw a considerable interest because they are independent indicators of atherogenicity. Triglyceride (TG)-rich lipoproteins (chylomicron and VLDL) are not considered to be atherogenic but they are related to the metabolism of HDL cholesterol and indirectly related to coronary heart disease (CHD). LDL can of itself be atherogenic but the oxidative products of this lipoprotein are more detrimental. HDL cholesterol has been considered to be a favorable cholesterol. The so-called 'causalist view' claims that HDL traps excess cholesterol from cellular membranes and transfers it to TG-rich lipoproteins that are subsequently removed by hepatic receptors. In the so-called 'noncausalist view', HDL does not interfere directly with cholesterol deposition in the arterial wall but instead reflects he metabolism of TG-rich lipoproteins and their conversion to atherogenic remnants. Approximately 70-80% of the human population shows an effective feedback control mechanism in cholesterol homeostasis. Type of dietary fat has a significant effect on the lipoprotein cholesterol metabolism and atherosclerosis. Generally, saturated fatty acids elevate and PUFA lower serum cholesterol, whereas MUFA have no specific effect. EPA and DHA inhibit the synthesis of TG, VLDL and LDL, and may have favourable effects on some of the risk factors. Phospholipids, particularly lecithin, have an antiatherosclerotic effect. Essential phospholipids (EPL) may enhance the formation of polyunsaturated cholesteryl ester (CE) which is less sclerotic and more easily dispersed via enhanced hydrolysis of CE in the arterial wall. Also, neutral fecal steroid elimination may be enhanced and cholesterol absorption reduced following EPL treatment. Antioxidants protect lipoproteins from oxidation, and cells from the injury of toxic, oxidized LDL. The rationale for lowering of serum cholesterol is the strong association between elevation of plasma or serum cholesterol and CHD. Cholesterol-lowing, especially LDL cholesterol, to the target level could be achieved using diet and combination of drug therapy. Information on the link between cholesterol and CHD has decreased egg consumption by 16-25%. Some clinical studies have indicated that dietary cholesterol and egg have a significant hypercholesterolemic effect, while others have indicated no effect. These studies differed in the use of purified cholesterol or cholesterol in eggs, in the range of baseline and challenge cholesterol levels, in the quality and quantity of concomitant dietary fat, in the study population demographics and initial serum cholesterol levels, and clinical settings. Cholesterol content of eggs varies to a certain extent depending on the age, breed and diet of hens. However, egg yolk cholesterol level is very resistant to change because of the particular mechanism involved in yolk formation. Egg yolk contains a factor of factors responsible for accelerated cholesterol metabolism and excretion compared with crystalline cholesterol. One of these factors could be egg lecithin. Egg lecithin may not be as effective as soybean lecithin in lowering serum cholesterol level due probably to the differences of fatty acid composition. However, egg lecithin may have positive effects in hypercholesterolemia by increasing serum HDL level and excretion of fecal cholesterol. The association of serum cholesterol with egg consumption has been widely studied. When the basal or control diet contained little or no cholesterol, consumption of 1 or 2 eggs daily increased the concentration of plasma cholesterol, whereas that of the normolipemic persons on a normal diet was not significantly influenced by consuming 2 to 3 eggs daily. At higher levels of egg consumption, the concentration of HDL tends to increase as well as LDL. There exist hyper-and hypo-responders to dietary (egg) cholesterol. Identifying individuals in both categories would be useful from the point of view of nutrition guidelines. Dietary modification of fatty acid composition has been pursued as a viable method of modifying fat composition of eggs and adding value to eggs. In many cases beneficial effects of PUFA enriched eggs have been demonstrated. Generally, consumption of n-3 fatty acids enriched eggs lowered the concentration of plasma TG and total cholesterol compared to the consumption of regular eggs. Due to the highly oxidative nature of PUFA, stability of this fat is essential. The implication of hepatic lipid accumulation which was observed in hens fed on fish oils should be explored. Nutritional manipulations, such as supplementation with iodine, inhibitors of cholesterol biosynthesis, garlic products, amino acids and high fibre ingredients, have met a limited success in lowering egg cholesterol.

Xylooligo당이 고콜레스테를 식이 횐쥐에서 간조직 HMG-CoA Reductase 활성과 지질 초성에 미치는 영향 (Effects of Dietary Xylooligosaccharides on HMG-CoA Reductase Activity and Lipid Cmposition of Liver in Rat Fed High Cholesterol Diets)

  • 김성옥;최정화;홍희진;주길재;이인구;이순재
    • 한국식품영양과학회지
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    • 제30권6호
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    • pp.1190-1196
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    • 2001
  • 고콜레스테롤 식이 횐쥐에서 xylooligo당이 간장에서의 콜레스테롤대사에 미치는 영향을 관찰하였다. 실험동물은 100$\pm$10g의 Sprague-Dawley 횐쥐를 이용하여 정상 식이군과 1% 고콜레스테롤 실험군으로 나누고 다시 실험군은 1%의 고콜레스테롤 식이에 xylooligo당을 0%, 5%, 10% 및 15% 농도 첨가군(C, C5XO, C10XO 및 C15XO군)으로 나누어 4주간 자유섭식시킨 후 콜레스테롤 대사 개선효과를 알아보았다. 간조직중의 중성지방과 콜레스테롤함량은 정상군에 비해 C군에서는 각각 3.9배, 20배씩 증가되었으며 C군에 비해 C10XO군은 거의 절반으로 감소되었다. 간조직의 HMG-CoA reductase 활성은 정상군에 비해 C군은 45% 감소되었으나, xylooligo당 공급군에서는 정상군 수준이었다. 간조직중의 지방산 조성은 oleic acid( $C_{18:1}$)과 linoleic acid( $C_{18:2}$)은 정상군에 비해 C군에서 유의적(p<0.05)으로 증가되었고, ara chidonic acid( $C_{20:4}$)는 감소되었으나 xylooligo당 공급으로 증가되었다. 총포화지방산(SFA)은 정상군에 비해 고콜레스테롤 식이로 인해 감소되 었으나, xylooligo당 공급으로 정상화되었다. 고콜레스테롤군에서는 총 단일불포화지방산(MUFA)은 증가되었으나, xylooligo당 공급으로 감소되었다. 항혈전지수인 n-3/n-6 지방산 비는 정상군에 비해 C군에서 감소되었으나, xylooligo당 10% 공급군에서는 C군에 비해 유의적으로 증가하였다. 결론적으로 식이 xylooligo당은 고콜레스테롤 식이로 인한 고콜레스테롤 혈증이나 고지혈증의 위험인자인 콜레스테롤을 감소시킬 수 있는 콜레스테롤 대사 개선 기능이 우수하므로 기능성 식품 신소재나 식이섬유의 대용품으로도 활용될 수 있으리라 생각된다.다.

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LJ-1888, a selective antagonist for the A3 adenosine receptor, ameliorates the development of atherosclerosis and hypercholesterolemia in apolipoprotein E knock-out mice

  • Park, Jong-Gil;Jeong, Se-Jin;Yu, Jinha;Kim, Gyudong;Jeong, Lak Shin;Oh, Goo Taeg
    • BMB Reports
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    • 제51권10호
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    • pp.520-525
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    • 2018
  • Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for $A_3$ AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out ($ApoE^{-/-}$) mice who are fed a western diet. Plaque formation was significantly lower in $ApoE^{-/-}$ mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of $ApoE^{-/-}$ mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in $ApoE^{-/-}$ mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for $A_3$ AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.

양춘사 추출물이 HepG2 세포에서 콜레스테롤 합성에 미치는 효과 (Effects of Amomum Villosum Extracts on Cholesterol Synthesis in HepG2 Cells)

  • 김하림;김예슬;최한별;우수현;권강범
    • 동의생리병리학회지
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    • 제38권1호
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    • pp.27-31
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    • 2024
  • Dried fruits of Amomum villosum Lour. have been used an korean medicine to treat digestive diseases for a long time. It has been reported that Amomum villosum extracts(AVE) have effects for diabetes and steatosis in experimental models. But we did not find the report about the cholesterol synthesis inhibition effects of AVE. The objective of this study is to clarify the inhibitory effect of AVE against oleic acid and glucose-induced hypercholesterolemia in HepG2 cells. The results show that AVE had a significant inhibitory effect against oleic acid and glucose-induced cholesterol accumulation. Those effects seem to be caused by inhibition of AVE on oleic acid and glucose-induced decrease of HMG CoA reductase, which is the rate-limiting enzyme for cholesterol biosynthesis in liver. It is believed that the results of this study can provide basic data for the drug and functional food development of hypercholesterolemia treatments.

Effects of citrus aglycone flavonoids, hesperetin and naringenin, on triacylglycerol metabolism in hamsters fed with a cholesterol diet

  • Cha, Jae-Young;Lee, Jin-Woo;Lee, Young-Choon;Cho, Young-Su
    • Advances in Traditional Medicine
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    • 제1권1호
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    • pp.28-36
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    • 2000
  • Effects of hesperetin and naringenin on the concentration of triacylglycerol in the serum and liver were studied in male golden hamster fed with the semipurified diet containing at 1% level of them for 3 weeks. The concentration of triacylglycerol in serum of the naringenin group decreased by 31%, whereas that in liver increased by 37% compared to the control group. The concentration of triacylglycerol in the serum and liver of the hesperetin group was slightly lower than the control group. The activity of microsomal phosphatidate phosphohydrolase in the liver, which is a key enzyme for biosynthesis of triacylglycerol, was significantly inhibited in the hesperetin group, whereas it was not affected in the naringenin group. The effect of hesperetin on phosphatidate phosphohydrolase was also measured in vitro. Hesperetin decreased the activity of phosphatidate phosphohydrolase with a dose-dependent manner. Both naringenin and hesperetin did not statistically affect the daily food consumption, body weight, liver weight, and total cholesterol in the serum. The observation accounts for the hypotriglyceridemic effect of hesperetin in the hyperlipidemic hamster.

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스타틴계 고지혈증치료제의 골절치료효과에 대한 분석 (Analysis on Statins for The Treatment of Bone Fracture)

  • 최병철
    • 약학회지
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    • 제53권4호
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    • pp.206-216
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    • 2009
  • 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (Statins) are potent inhibitors of cholesterol biosynthesis. Cholesterol-lowering therapy using statins significantly reduces the risk of coronary heart disease. Various discovery of statins as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Clinical and animal test results of statins focusing on the prevention and treatment of bone fractures was collected. Three independent literature searches were performed by using from January 1, 2002 to September 2008 for clinical and animal test results. Search term included statins, HMG-CoA reductase inhibitors, pleiotropic effects, fracture, osteoporosis and clinical and animal test. No consensus has been reached whether clinical use of statins has beneficial effects on bone health, partly due to lower statin concentrations because of first-pass metabolism by the liver. Experimental use of statins as stimulators of bone formation suggests that they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In conclusion, The use of statins in the prevention and treatment of bone fractures requires further study. But observational studies suggest that statins for decreasing bone fractures including osteoporosis have to be considered local direct administration like transdermal or subcutaneous type over oral adminstration.