• 제목/요약/키워드: cholesterol biosynthesis

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Alloxan 유도 당뇨성 흰쥐에서 조직 중 지질 수준 및 지방산 조성 변화에 관한 연구 (The Change of Tissue Lipid Levels and Fatty Acid Compositions by Alloxan-induced Diabetes in Rats)

  • 이준호;전인녀
    • 한국식품영양과학회지
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    • 제33권8호
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    • pp.1273-1278
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    • 2004
  • 당뇨병의 합병증 중 지질대사성 질환으로 유도되는 대사경로를 규명하고자 6주령의 흰쥐(Sprague-Dawley) 24마리를 3군으로 나누어 4주간 chemical pure diet로 사육하였다. 당뇨병을 유발하고자 alloxan을 20 mg/kg BW 또는 40 mg BW를 매주 1회 투여하였다. 혈당치를 측정하여 당뇨증상을 확인하였으며 혈청 및 간의 지질수준과 각 조직의 지방산 조성을 측정하여 당뇨병에 의한 지질대사의 변화를 비교 검토하였다. Alloxan 40 mg 투여군에서 심한 당뇨병 유발로 체중감소가 크게 나타났으며, 식이섭취량과 간중량/100 g BW도 다른 군에 비하여 유의적으로 높았다. 혈당의 변화는 alloxan 40 mg/kg BW 투여한 군이 다른 군에 비해 약 2배정도로 높게 나타나 당뇨병이 유발되었음을 확실하게 알 수 있었다. 혈청지질에서 cholesterol 함량은 alloxan 40 mg/kg BW 투여한 군에서 다른 군보다 다소 증가된 경향을 보였다. Triglyceride도 역시 alloxan 투여군에서 높은 경향으로 나타났다. 혈청 HDL-cholesterol은 군간의 유의적인 차이가 없었으며 HDL-/total cholesterol 비율도 군간에 유의적인 차이는 없었으나, 다른 군보다 alloxan 40 mg/kg BW을 투여한 군이 다소 높은 경향이었다. 간 지질에서 cholesterol 함량은 alloxan 40 mg/kg BW 투여군이 다른 군에 비해 유의적으로 낮았다. Triglyceride 함량은 군간에 유의적인 차이가 없었다. 각 조직의 인지질 지방산 조성을 보면 alloxan 40 mg/kg BW 투여군에서 lionleic acid는 증가하고 반면 arachidonic acid는 감소되어 그 결과 arachidonic/linoleic acid의 비율이 낮은 경향을 보였으며 특히 혈청과 비장에서는 그 경향이 뚜렷하여 유의적인 차이를 나타냈다. 이상의 결과를 종합하면, 당뇨병이 유도된 흰쥐에서 간의 중량 및 혈청의 지질이 증가되었고, 조직의 인지질에서 desaturation이 억제되었으므로 그로 인하여 지질대사에 관련된 합병증이 유도되는 것으로 판단되었다.

오미자(五味子) 클로로포름 분획물이 이상지질혈증 생쥐의 지질대사 및 간 조직 유전자 변화에 미치는 영향 (The Effects of Schizandrae Fructus Chloroform Fraction on Gene Expression in Liver Tissue of Dyslipidemic Mice)

  • 신윤리;김영균;김경민
    • 한방비만학회지
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    • 제15권2호
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    • pp.111-122
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    • 2015
  • Objectives: Schizandrae fructus (Schizandra chinensis) is one of very common herbs, it is known as natural antioxidants, anti-inflammatory agent. Also some reports show that its extract works to regulate of dyslipidemia. This study was designed to investigate the effects of Schizandrae fructus chloroform fraction (SFCF) on serum lipid levels in dyslipidemic mice. Methods: The levels of total cholesterol, high density lipoprotein-cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting blood glucose in serum were measured. Histopathological and gene expression changes in liver tissue were also observed. Results: Oral administration of SFCF lowered levels of total cholesterol and triglyceride, which were elevated by high-fat diet. But SFCF did not affect on weight changes and serum AST, ALT levels in dyslipidemic mice. After carrying out gene ontological analysis, large numbers of genes in high-fat diet group were up-(347) or down-regulated (235). In SFCF treated mice, some changed expression of the genes was restored to normal levels, with a recovery rate of 17%. And it seems that fatty acid biosynthesis pathway was one of important key pathways to recovery. Conclusions: SFCF has beneficial effect on dyslipidemia, and could be used to prevent and treat cardiovascular disease.

고지방 식이를 섭취한 흰쥐에 있어서 Xylooligo당이 간의 HMG-CoA Reductase 활성 및 간조직의 형태학적 변화에 미치는 영향 (Effects of Dietary Xylooligosaccharides on Hepatic HMG-CoA Reductase Activity and Morphological Exchange of liver in Rats Fed High Fat Diets)

  • 손효현;이순재
    • Journal of Nutrition and Health
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    • 제35권10호
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    • pp.1015-1022
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    • 2002
  • This study was conducted to examine the effects of dietary xylooligosaccharides on hepatic HMG-CoA reductase activity and morphological exchange of liver in rats fed high fat diet. Sprague-Dawley male rats weighing 100 $\pm$ 10 g were randomly divided into four groups, two normal diets and two high fat diets containing 1% cholesterol and 10% lard. Two normal diets were classified into a basal diet (normal group) and 10% xylooligosaccharide diet (NX group). The high fat diet groups were classified into a HF group without xylooligosaccharides diet and HFX group supplemented 10% xylooligosacchride diet. Experimental diets were fed ad libidum to the rats for 4 weeks and then they were sacrificed. The body weight of high fat diet (HF group) was increased more than that of normal group, but it was significantly decreased by xylooligosacchrides supplementation. The food intake was not significantly different among the all groups. The weight of liver, small intestine and cecum of all xylooligosaccharide supplemented groups were significantly heavier than those of normal and HF groups. The activity of hepatic HMG-CoA reductase, a rate limiting enzyme of cholesterol biosynthesis, in xylooligosaccharide supplemented groups was higher than that of HF group. Light micrographs revealed that the structures of hepatocytes in xylooligosaccharide supplemented groups were preserved well, compared to HF group. The xylooligosaccharide supplementation exerted a lipid-lowering action by decreasing cholesterol and triglycerides contents in hepatic tissue. In conclusion, the activity of hepatic HMG-CoA reductase and damage of liver in rats fed high fat diets were improved by dietary xylooligosaccharides.

Cholesterol side-chain cleavage enzyme deficiency caused by a novel homozygous variant in P450 sidechain cleavage enzyme gene (CYP11A1) in a 46,XX Korean girl

  • Ye Ji Kim;Sun Cho;Hwa Young Kim;Young Hwa Jung;Jung Min Ko;Chang Won Choi;Jaehyun Kim
    • Journal of Genetic Medicine
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    • 제20권1호
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    • pp.25-29
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    • 2023
  • The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

Brassinosteroid의 대사공학 (Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways)

  • 이미옥;송기홍;이현경;정지윤;최빛나리;최성화
    • 한국식물생명공학회:학술대회논문집
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    • 한국식물생명공학회 2002년도 추계학술대회
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    • pp.69-75
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus It is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

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Brassinosteroid의 대사공학 (Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways)

  • 이미옥;송기홍;이현경;정지윤;최빛나리;최성화
    • 한국식물생명공학회:학술대회논문집
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    • 한국식물생명공학회 2002년도 춘계학술대회
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    • pp.69-75
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were Shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

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Brassinosteroid의 대사공학 (Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways)

  • 이미옥;송기홍;이현경;정지윤;최빛나리;최성화
    • Journal of Plant Biotechnology
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    • 제29권2호
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    • pp.139-144
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd /dwf3 were shown to be blocked in D$^4$reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bril/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRIl could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

Improved mevinolic acid (MA) production by the immobilized cells, and the establishment of on-line measurement system for fermentation parameters using vent gas analyzer

  • 송성기;김경희;김명진;이상종;장용근;정연호;정용섭;전계택
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2003년도 생물공학의 동향(XII)
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    • pp.223-227
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    • 2003
  • Mevinolic acid (MA), a secondary metabolite produced by a filamentous fungus Aspergillus terreus, is acidic form of lovastatin which has been identified as a powerful cholesterol-lowering agent in humans. When immobilized cell culture was performed, MA production was about 5.3-fold higher than the parallel suspended cell culture. Although the immobilized cells proliferated slowly during exponential in comparison with the suspended cells, oxygen uptake rate and oxygen mass transfer coefficient of the immobilized cell culture were about 1.3- and 2.5- fold higher respectively than those of the parallel suspended cell culture. From these results, it was concluded that MA biosynthesis was closely dependent on the cell growth rate, morphology and oxygen availability.

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흰쥐의 담즙 상실이 혈청 지질과 Gastrin 대사에 미치는 영향 (Effect of Bile Deprivation on Serum Lipids and Gastrin in the Rat)

  • 송경희
    • Journal of Nutrition and Health
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    • 제20권1호
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    • pp.46-53
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    • 1987
  • The effect of bile deprivation on serum lipid and gastrin contents was investigat\ulcornered after choledocho-urinary cystostomy in Sprague-Dawley rats. Bile deprivated rats were compared with sham operated control group. Gastrin levels in serum and antral tissue were measured and serum lipid concentrations were also measured. Gastrin levels of serum and tissue after bile deprivation were increased significantly compared with those of the controL At the end of 1st and 2nd week after bile deprivation, serum cholesterol and triglyceride contents were significantly lower han those of the control. By 4th week, there was no significant difference between two groups. Increases in serum and antral gastrin levels temporarily coincided well with decreases in serum lipid contents after bile deprivation. These results suggest that there is increase in biosynthesis and release of gastrin and decrease in fat absorption at early stage of bile deprivation.

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식물 추출물로 부터 3-hydroxy-3-rnethylglutaryl-Coenzyme A Reductase의 활성저해제 탐색 (In vitro screening of 3-hydroxy-3-methy1g1utaryl-Coenzyme A reductase inhibitor from plant extracts)

  • 이윤형;신용목
    • KSBB Journal
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    • 제6권1호
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    • pp.55-61
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    • 1991
  • The objective of this in vitro study is to screen a possible inhibitor, originated from some chinese herb medicines, of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase that is the major regulatory enzyme of hepatic cholesterol biosynthesis. Fourteen kinds of herbal plant were extracted with water and evaporated for prescreening. The methanol extracts of the effective 3 kinds (9 species) were fractionated with chloroform, ethylacetate, butanol and water, and vacuum evaporated. The degree of inhibition of the extracts to HMG-CoA reductase activity was calculated by the spectrophotometric method using microsomal protein of Saccharomyces cerevisiae ATCC 42949 as an enzyme source. Among these samples, marked inhibitory effects were observed in the extracts of ethylacetate and chloroform fractions of the Rosa rugosa roots, and those of butanol, ehtylacetate and water fractions of pine leaves. Also, the inhibitory effects of the extracts obtained from buckwheat shell and the roots of Rosaceae were found.

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