• 제목/요약/키워드: Acyl-CoA oxidase

검색결과 19건 처리시간 0.023초

Crystal Structure of Acyl-CoA Oxidase 3 from Yarrowia lipolytica with Specificity for Short-Chain Acyl-CoA

  • Kim, Sangwoo;Kim, Kyung-Jin
    • Journal of Microbiology and Biotechnology
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    • 제28권4호
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    • pp.597-605
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    • 2018
  • Acyl-CoA oxidases (ACOXs) play important roles in lipid metabolism, including peroxisomal fatty acid ${\beta}$-oxidation by the conversion of acyl-CoAs to 2-trans-enoyl-CoAs. The yeast Yarrowia lipolytica can utilize fatty acids as a carbon source and thus has extensive biotechnological applications. The crystal structure of ACOX3 from Y. lipolytica (YlACOX3) was determined at a resolution of $2.5{\AA}$. It contained two molecules per asymmetric unit, and the monomeric structure was folded into four domains; $N{\alpha}$, $N{\beta}$, $C{\alpha}1$, and $C{\alpha}2$ domains. The cofactor flavin adenine dinucleotide was bound in the dimer interface. The substrate-binding pocket was located near the cofactor, and formed at the interface between the $N{\alpha}$, $N{\beta}$, and $C{\alpha}1$ domains. Comparisons with other ACOX structures provided structural insights into how YlACOX has a substrate preference for short-chain acyl-CoA. In addition, the structure of YlACOX3 was compared with those of medium- and long-chain ACOXs, and the structural basis for their differences in substrate specificity was discussed.

Geness for degradation of storage oil and their application to oil biotechnology

  • Nishimura, Mikio;Hayashi, Makoto;Kato, Akira;Mano, Shoji;Hayashi, Hiroshi;Yamaguchi, Katushi;Nito, Kazumasa;Fukao, Youichiro
    • 한국식물학회:학술대회논문집
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    • 한국식물학회 1999년도 제13회 식물생명공학심포지움 New Approaches to Understand Gene Function in Plants and Application to Plant Biotechnology
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    • pp.37-40
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    • 1999
  • cDNAs for long- and short-chain acyl-CoA oxidases in fatty acid $\beta$-oxidation were isolated and were characterized their enzymatical and molecular properties. Both oxidases were exclusively localized in glyoxysomes, indicating that glyoxysomes can completely metabolize fatty acids to acyl-CoA by their cooperative action. In order to clarify the regulatory mechanisms underlying degradation of storage oil, we tried to obtain glyoxysome-deficient mutants of Arabidopsis. We screened 2,4-dichlorophenoxybutyric acid (2,4-DB) mutants of Arabidopsis which have defects in glyoxysomal fatty acid $\beta$-oxidation. Four mutants can be classified as carrying alleles at three independent loci, which we designated pedl, ped2, and ped3, respectively (where ped stands for peroxisome defective). The characteristics of these ped mutants are described.

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Characterization of Acyl-CoA Oxidases from the Lipolytic Yeast Candida aaseri SH14

  • Ibrahim, Zool Hilmi;Bae, Jung-Hoon;Sung, Bong Hyun;Kim, Mi-Jin;Rashid, Ahmad Hazri Ab;Sohn, Jung-Hoon
    • Journal of Microbiology and Biotechnology
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    • 제32권7호
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    • pp.949-954
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    • 2022
  • The lipolytic yeast Candida aaseri SH14 contains three Acyl-CoA oxidases (ACOXs) which are encoded by the CaAOX2, CaAOX4, and CaAOX5 genes and catalyze the first reaction in the β-oxidation of fatty acids. Here, the respective functions of the three CaAOX isozymes were studied by growth analysis of mutant strains constructed by a combination of three CaAOX mutations in minimal medium containing fatty acid as the sole carbon source. Substrate specificity of the CaAOX isozymes was analyzed using recombinant C. aaseri SH14 strains overexpressing the respective genes. CaAOX2 isozyme showed substrate specificity toward short- and medium-chain fatty acids (C6-C12), while CaAOX5 isozyme preferred long-chain fatty acid longer than C12. CaAOX4 isozyme revealed a preference for a broad substrate spectrum from C6-C16. Although the substrate specificity of CaAOX2 and CaAOX5 covers medium- and long-chain fatty acids, these two isozymes were insufficient for complete β-oxidation of long-chain fatty acids, and therefore CaAOX4 was indispensable.

The Effects of Docosahexaenoic Acid Oil and Soybean Oil on the Expression of Lipid Metabolism Related mRNA in Pigs

  • Liu, B.H.;Wang, Y.C.;Kuo, C.F.;Cheng, W.M.;Shen, T.F.;Ding, Shih-Torng
    • Asian-Australasian Journal of Animal Sciences
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    • 제18권10호
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    • pp.1451-1456
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    • 2005
  • To study the acute effect of dietary docosahexaenoic acid (DHA, $C_{22:6}$) on the expression of adipocyte determination and differentiation-dependent factor 1 (ADD1) mRNA in pig tissues, weaned, crossbred pigs (28 d of age) were fed with either 10% (on as-fed basis) tallow (high stearic acid), soybean oil (high linoleic acid), or high DHA algal oil for 2 d. The plasma and liver DHA reflected the composition of the diet. The adipose tissue and skeletal muscle DHA did not reflect the diet in the short term feeding. The results also showed that the diet containing 10% algal DHA oil significantly decreased the total plasma cholesterol (39%) and triacylglycerol (TG; 46%) in the pigs. Soybean oil significantly decreased plasma TG (13.7%; p<0.05), but did not have an effect on plasma cholesterol. The data indicate that different dietary fatty acid compositions have different effects on plasma lipids. The ADD1 mRNA was decreased (p<0.05) in the liver of DHA oil-treated pigs compared with the tallow-treated pigs. The diets did not have significant effect on the ADD1 mRNA in adipose tissue. Addition of algal DHA oil in the diet increased acyl CoA oxidase (ACO) mRNA concentration in the liver, suggesting that dietary DHA treatment increases peroxisomal fatty acid oxidation in the liver. However, dietary soybean oil supplementation did not affect mRNA concentrations of ADD1 or ACO in the tissues of pigs. Because ADD1 increases the expression of genes associated with lipogenesis, and ACO is able to promote fatty acid oxidation, feeding DHA oil may change the utilization of fatty acids through changing the expression of ADD1 and ACO. Therefore, feeding pigs with high DHA may lead to lower body fat deposition.

Liver PPAR${\alpha}$ and UCP2 are Involved in the Regulation of Ovariectomy-Induced Adiposity and Steatosis by Swim Training

  • Jeong, Sun-Hyo;Yoon, Mi-Chung
    • 대한의생명과학회지
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    • 제16권4호
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    • pp.239-246
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    • 2010
  • It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor ${\alpha}$ (PPAR${\alpha}$) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPAR${\alpha}$ and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPAR${\alpha}$ and its target genes responsible for peroxisomal fatty acid ${\beta}$-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPAR${\alpha}$ and UCP2 in female obese mice.

고지방 식이 유도 비만 마우스 모델에서 황정 추출물의 지방질 및 에너지 대사 관련 유전자에 대한 효능 연구 (Effects of Polygonatum sibiricum rhizome extract on lipid and energy metabolism in high-fat diet-induced obese mice)

  • 전우진;김지영;오익훈;이도섭;손서연;서윤지;연승우;강재훈
    • 한국식품과학회지
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    • 제49권2호
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    • pp.192-202
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    • 2017
  • 황정 주정 추출물 ID1216의 고지방 식이 유도 비만 마우스에서의 체중 증가 억제 효과에 대한 분자생물학적 기전을 확인하고자 단백질과 mRNA 수준에서 지질 및 에너지 대사 관련 유전자들의 발현 변화를 관찰하였다. 본 연구에서 확인된 지표들 간의 상호 작용 및 ID1216의 조절 여부에 관해 Fig. 10에 나타내었다. 실험 결과 ID1216은 고지방 식이 유도 비만 마우스에서 체중 증가 억제를 나타내었으며, 비만 대사 관련 pathway의 상위 유전자로 사료되는 SIRT1과 AMPK의 발현을 조절하는 것으로 나타났다. 활성화된 SIRT1과 AMPK는 $PGC1{\alpha}$의 활성화에 관여하고, 이를 통해 열 발산 대사와 관련된 UCP 단백질과 핵 수용체 단백질인 $PPAR{\alpha}$의 발현이 백색지방, 갈색지방, 간 및 근육에서 증가되는 것이 확인되었다. 각 조직 별로 RT-PCR을 진행한 결과에서는 $PPAR{\alpha}$의 하위 유전자인 aP2, ACO, Acadl, Acadm, CPT1a, CPT1b의 mRNA 발현 수준을 향상시켜 주어 ID1216이 지방산 산화 대사인 ${\beta}$-oxidation의 활성화에 기여할 가능성을 보여주었다. 이와는 별개로 ID1216은 중성지질을 분해하는 것으로 알려진 ATGL의 mRNA 발현 또한 증가시키는 것으로 확인되었다. 본 연구를 통해 ID1216이 조직에 따라 지질 및 에너지 대사와 관련된 인자의 발현에 영향을 주는 체중 조절에 효과적인 소재임을 알 수 있었다. 또한 비만 치료제와의 기전적 차별성과 생약 특유의 섭취 안전성을 특징으로 하는 체중 또는 체지방 조절 기능성 소재로의 활용 가능성도 충분히 가지고 있음을 확인할 수 있었다.

제2형 당뇨병 모델 마우스에서 ginsenoside Rg1의 항당뇨 효과 (Antihyperlipidemic Effect of Ginsenoside Rg1 in Type 2 Diabetic Mice)

  • 박재홍;이지연;여지영;남정수;정명호
    • 생명과학회지
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    • 제21권7호
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    • pp.932-938
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    • 2011
  • Ginsenoside Rg1은 인삼에서 분리한 약물학적인 활성을 가지는 물질이다. 본 연구는 Rg1이 제2형 당뇨병 모델 동물에서 혈당과 지질대사에 유익한 효과를 가지는지를 확인하기 위한 목적으로 수행되었다. 10주령의 db/db 마우스에 Rg1을 10 mg/kg 농도로 15일간 경구투여한 결과 공복혈당이 감소하였고, 포도당 내성이 개선되었다. 특히 혈중 중성지방과 유리지방산이 유의적으로 감소하였고 혈중 HDL-콜레스테롤이 증가되었다. 또한 chimeric GAL4-PPAR${\alpha}$ receptor 활성 프로모터를 활성화시켰고 PPAR${\alpha}$ gene인 CPT-1 (carnitine palmitoyltransferase-1)과 ACO (acyl-CoA oxidase)의 발현을 증가시켰는데 이것으로 Rg1의 지질대사 개선이 PPAR${\alpha}$ 활성에 의한 지방산 산화에 의한 것임을 확인할 수 있었다. 모든 결과를 종합해 볼 때, Rg1은 제2형 당뇨병과 관련된 고혈당증과 고지혈증에 유용한 효과를 가짐을 확인하였다.

Troglitazone Lowers Serum Triglycerides with Sexual Dimorphism in C57BL/6J Mice

  • Jeong Sun-Hyo;Yoon Mi-Chung
    • 대한의생명과학회지
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    • 제12권2호
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    • pp.65-72
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    • 2006
  • Thiazolidinediones (TZDs) are widely used antidiabetic drugs that activate the nuclear peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$, and thereby improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin resistance, and cardiovascular disease. To determine whether the $PPAR{\gamma}$ ligand troglitazone regulates lipid metabolism with sexual dimorphism, we examined the effects of troglitazone on circulating lipids, body weight and the expression of hepatic genes responsible for lipid metabolism in both sexes of C57BL/6J mice. Compared to mice fed a low fat control diet, both sexes of mice fed a troglitazone-treated low fat diet for 14 weeks did not exhibit changes in body weight gain, serum total cholesterol, HDL-cholesterol and LDL-cholesterol levels. However, serum triglycerides were significantly reduced in both sexes of mice, although these effects were more pronounced among males. Furthermore, troglitazone regulated the expression of hepatic genes critical for lipid and lipoprotein metabolism, the magnitudes of which were much higher in males compared to females, as evidenced by results for increased acyl-CoA oxidase and decreased apolipoprotein C-III mRMA levels. These results suggest that $PPAR{\gamma}$ activator troglitazone may exert sexually dimorphic control of serum triglycerides in part through the differential activation of $PPAR{\gamma}$ in liver between male and female mice.

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Oxidation of fatty acid may be enhanced by a combination of pomegranate fruit phytochemicals and acetic acid in HepG2 cells

  • Kim, Ji Yeon;Ok, Elly;Kim, You Jin;Choi, Kyoung-Sook;Kwon, Oran
    • Nutrition Research and Practice
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    • 제7권3호
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    • pp.153-159
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    • 2013
  • We investigated whether the combination of phytochemicals and acetic acid in the form of fruit vinegar provides an additive effect on changes of mRNA levels related to fatty acid oxidation in human hepatocyte (HepG2). Among the seven fruit vinegars (Rubuscoreanus, Opuntia, blueberry, cherry, red ginseng, mulberry, and pomegranate) studied, treatment of HepG2 with pomegranate vinegar (PV) at concentrations containing 1 mM acetic acid showed the highest in vitro potentiating effect on the mRNA expression levels of peroxisome proliferator-activated receptor ${\alpha}$, carnitinepalmitoyl transferase-1, and acyl-CoA oxidase compared to the control group (P < 0.05). Reversed-phase liquid chromatography in combination with quadrupole time-of-flight mass spectrometry analysis revealed four potential compounds (punicalagin B, ellagic acid, and two unidentified compounds) responsible for altered gene expression in HepG2 cells treated with PV as compared with the others. Further investigations are warranted to determine if drinking PV beverages may help to maintain a healthy body weight in overweight subjects.