• Title/Summary/Keyword: Liver Fatty Acids

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Evaluation of Luminescent P450 Analysis for Directed Evolution of Human CYP4A11

  • Choi, Seunghye;Han, Songhee;Lee, Hwayoun;Chun, Young-Jin;Kim, Donghak
    • Biomolecules & Therapeutics
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    • v.21 no.6
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    • pp.487-492
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    • 2013
  • Cytochrome P450 4A11 (CYP4A11) is a fatty acid hydroxylase enzyme expressed in human liver. It catalyzes not only the hydroxylation of saturated and unsaturated fatty acids, but the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a regulator of blood pressure. In this study, we performed a directed evolution analysis of CYP4A11 using the luminogenic assay system. A random mutant library of CYP4A11, in which mutations were made throughout the entire coding region, was screened with luciferase activity to detect the demethylation of luciferin-4A (2-[6-methoxyquinolin-2-yl]-4,5-dihydrothiazole-4-carboxylic acid) of CYP4A11 mutants in Escherichia coli. Consecutive rounds of random mutagenesis and screening yielded three improved CYP4A11 mutants, CP2600 (A24T/T263A), CP2601 (T263A), and CP2616 (A24T/T263A/V430E) with ~3-fold increase in whole cells and >10-fold increase in purified proteins on the luminescence assay. However, the steady state kinetic analysis for lauric acid hydroxylation showed the significant reductions in enzymatic activities in all three mutants. A mutant, CP2600, showed a 51% decrease in catalytic efficiency ($k_{cat}/K_m$) for lauric acid hydroxylation mainly due to an increase in $K_m$. CP2601 and CP2616 showed much greater reductions (>75%) in the catalytic efficiency due to both a decrease in $k_{cat}$ and an increase in Km. These decreased catalytic activities of CP2601 and CP2616 can be partially attributed to the changes in substrate affinities. These results suggest that the enzymatic activities of CYP4A11 mutants selected from directed evolution using a luminogenic P450 substrate may not demonstrate a direct correlation with the hydroxylation activities of lauric acid.

Physiological Activity of $\omega3$ Polyunsaturated Fatty Acids in Dark Fleshed Fishes II. Antioxidative Effect on Lipid Peroxidation in Rats ($\omega3$ 고도불포화지방산의 생리활성에 관한 연구 II. 과산화지질에 대한 항산화 작용)

  • CHOI Jin-Ho;Byun Dae-Seok
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.22 no.2
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    • pp.109-114
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    • 1989
  • To compare antioxidant action of u 3 polyunsaturated fatty acid (PUFA) on lipid peroxidation in rats, the formation of malondialdehyde (MDA) and membranes of liver and brain and activities of antioxidant-related enzymes such as catalase, glutathione peroxidase, and superoxide dismutase (SOD) in blood, were studied. Malondialdehyde contents of $\omega3$ PUFA and sardine oil groups were significantly decreased compared with lard group as control (p<0.05). Catalase and superoxide dismutase showed higher activities in $\omega3$ PUFA and sardine oil groups than those of lard control group. These findings suggest that fish oil has a inhibitory effect on formation of lipid peroxides in blood and membranes of rats.

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Effects of Drynariae Rhizoma Hot Water Extract on Metabolic Improvement in the Ovariectomized Rat Model of Menopause (골쇄보 열수추출물의 급여가 갱년기 유도 흰쥐의 대사개선 효능에 미치는 영향)

  • Kang, Mi Young;Chung, Soo Im;Lee, Sang Chul
    • Korean Journal of Medicinal Crop Science
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    • v.24 no.5
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    • pp.370-374
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    • 2016
  • Background: Many menopausal women suffer from health problems including metabolic diseases such as dyslipidemia and osteoporosis. Thus they need natural products and functional foods particularly highly nutritional food products, that can help alleviate these diseases. This study was carried out to determine the effect of Drynariae Rhizoma water extract on the lipid and bone metabolism of ovariectomized Sprague-Dawley rats. Methods and Results: The animals were randomly divided into six dietary groups comprising SHAM-operated rats, OVX rats (normal diet), and OVX-DR rats (Drynariae Rhizoma extract). After 8 weeks, plasma, liver, and fat samples were collected to analyze the lipid metabolism, plasma Ca, alkaline phosphatase (ALP), osteocalcin and C-terminal telopeptide (CTx) concentrations, which are biochemical makers of bone metabolism. The left femurs of rats were also collected for histological analyses. OVX counteracted menopause induced body weight gain, as well as increases in triglycerides, total cholesterol, and free fatty acids. The Drynariae Rhizoma group showed low levels of triglycerides, high HDL-cholesterol, and decreased lipogenesis based on activity of the lipid-regulating enzymes (fatty acid synthase and malic enzyme). Decreased serum levels of ALP and osteocalcin were observed in Drynariae Rhizoma group. Conclusions: The results of this study show that Drynariae Rhizoma extract may effectively regulate hyperlipidemia and improve bone density.

Effects of Foeniculi fructus Water Extracts on Activities of Key Enzymes of Lipid Metabolism Related with Obesity (회향종자(Foeniculi fructus)의 물 추출물이 비만과 관련된 지질대사 효소의 활성에 미치는 효과)

  • Seo, Dong-Joo;Kim, Tae-Hyuck;Kim, Hyun-Sook;Choe, Myeon
    • Korean Journal of Plant Resources
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    • v.24 no.2
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    • pp.181-188
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    • 2011
  • This study was carried out to estimate beneficial effects of Foeniculi fructus water extract on activities of key enzymes such as lipoprotein lipase (LPL), acyl-CoA synthetase (ACS), and hormone sensitive lipase (HSL) on lipid metabolism related with obesity. LPL and ACS were extracted from the epididymal adipose tissue and liver of C57BL/6J normal and obese mouse. Foeniculi fructus water extract treatment significantly reduced the activity of normal and obese LPL. When 100 ppm of Foeniculi fructus water extracts were tested, they decreased obese LPL activity by 12.0%. Foeniculi fructus water extract activated obese ACS activity by 7-fold compared with control at 1,000 ppm concentration. Expression of HSL mRNA was increased in Foeniculi fructus water extracts treated cells compared with non treated cells. All things considered, Foeniculi fructus water extract efficiently inhibits the influx of fatty acid into the cell, and activates metabolic process that uses fatty acids flowing as an energy source. Thus, it suggest that Foeniculi fructus water extract may have great potential as a novel anti-obesity agent.

Effect of Sea Tangel Intake on Cytokine Production in Macrophage from Normal and Diabetic Mice (다시마섭취가 정상과 당뇨 생쥐 대식세포의 Cytokine 분비에 미치는 영향)

  • 조성희;양경미;배복선;임선아;유리나
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.5
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    • pp.952-959
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    • 1998
  • To investigate the effect of sea tangle on macrophage activity in normal and diabetic states, 10week old ICR mice were fed control(C) and sea tangle(S) diet containing 5%(w/w) cellulose and 13.6%(w/w) dry sea tangle for four weeks, after which two thirds of mice(CD and SD) were made diabetic by intramuscular injection of streptozotocin(150mg/kg bw). At 4th day after diabetes was apparent by urinary glucose, one half of diabetic mice(CDM and SDM) were treated with metformin(500mg/kg bw) orally. Peritoneal macrophages obtained from 3%-thioglycollate treated mice were cultured in the presence of lipopolysaccaride from Salmonella abortus equi(10$\mu\textrm{g}$/ml) for 24 hrs and tumor necrosis factor-$\alpha$(TNF$\alpha$), interleukin-1$\beta$(1L-1$\beta$)and prostaglandin E2(PGE2) were measured in culture media. Release of IL-1$\beta$and PGE2 from macrophage were increased in normal mice by sea tangle diet and had the same tedency in diabetic mice with or without metformin treatment although not statistically significant. Release of TNF$\alpha$ tended to be reduced by diabetes but were not changed significantly by sea tangle diet. Fatty acid compositions of macrophage and liver phospholipids showed that diabetes reduced arachidonic acid/linoleic acid ratio and sea tangle diet appeared to increase contentsof polyunsaturated fatty acids.

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Chemical Structure and Physiological Activity of Lignan Component in Sesame (참깨 리그난 성분의 화학구조와 생리활성)

  • 류수노;이은정;윤혜신;강삼식
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.48
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    • pp.65-71
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    • 2003
  • Sesame seed are one of the oldest oil-bearing crops known to man. Not only are they nutritious, they are physicologically beneficial. Because of these properties, the promotion of sesame as a crop is set to increase from now on. The lignan component of sesame, which has an antioxidative function, varies considerably. In addition, the seeds remain viable for longer than other crops. At low temperature, it has been reported that the seed remain viable for up to thirty years. This is due to the lignan content of the seeds. In the last twenty years, the mysteries of the natural chemistry of sesame seeds have been unravelled one by one. Up to now, the lignan component has been found to have an $\alpha$-tocopherol synergist effect, an anti-aging effect, a cancer suppressing effect, a hypertension reduction effect, an effect on the promotion of liver function, an effect on the control of the ration of unsaturated fat, and an effect on the synthesis of unsaturated fatty acids. The lignan component of sesame does not simply have an anti-oxidant function, but has diverse recently discovered physiological uses which make the study of lignan highly rewarding.

Phytochemical and Pharmacological Investigations on Moringa peregrina (Forssk) Fiori

  • Elbatran, Seham A.;Abdel-Salam, Omar M.;Abdelshfeek, Khaled A.;Nazif, Naglaa M.;Ismail, Shams I.;Hammouda, Faiza M.
    • Natural Product Sciences
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    • v.11 no.4
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    • pp.199-206
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    • 2005
  • Investigation of M. peregrina aerial parts revealed the isolation and identification of 4-flavonoidal compounds, quercetin, quercetin-3-0-rutinoside (rutin), chrysoeriol-7-0-rhamnoside 6,8,3',5'-tetramethoxy apigenin. The compounds were identified by TLC, PC, MS, and $H^1-NMR$. The fatty acids and unsaponifiable matter were studied. The $LD_{50}$ for M. peregrina was 113.4 mg/100g b.wt. Repeated intraperitoneal injection of 1/20 and 1/10 $LD_{50}$ (5.67 mg and 11.34 mg/100g b.wt.) of defatted alcoholic of M. peregrina for 30 days induced significant decrease in serum glucose, liver enzymes and lipid components. M. peregrina administered i.p., 30min prior to carrageenan at the above doses significantly inhibited the rat paw oedema response, In acute pain models, namely, the acetic acid-induced writing and hot-plate assay, M. peregrina exhibited marked analgesic properties. In addition, M. peregrina administered at time of indomethacin injection inhibited the development of gastric lesions in rats.

Antioxidative and Radical Scavenging Properties of Extracts from Geum japonicum

  • Cho, Kang-Jin;Kim, Jong-Bum;Kim, Jung-Bong;Kim, Dong-Gil;Kim, Haeng-Ran;Hwang, Young-Soo
    • Journal of Applied Biological Chemistry
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    • v.44 no.2
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    • pp.87-91
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    • 2001
  • Extracts from Geum japonicum (Bammu in Korean) were analyzed for their antioxidative activities and scavenging effects on free radicals. The ethyl acetate fraction of G. japonicum methanol extract (EFGJ) showed a remarkable scavenging activity on the 1,1-diphenyl-2-picrylhydrazyl radical. EFGJ also showed excellent antioxidative activity on linoleic acid during long-period storage and on rat liver microsome peroxidation system, and good anti-peroxidation effect on lipid in Rancimat system using lard, palm oil, and perilla oil, as compared with BHT and ${\alpha}$-tocopherol. Varying effects of antioxidative activity of the EFGJ on various fatty acids were observed. The prevention of linoleic acid and linolenic acid peroxidation was superior to ${\alpha}$-tocopherol, but inferior to BHT. The methanol extract of G. japonicum did not show mutagenicity as revealed through SOS chromotest. Based on the results, the extracts of G. japonicum may be useful source as natural antioxidants.

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The Metabolic Effects of Rice Bran and Vegetable Collulose Supplemented Diets on Albino Rats( III ) -Especially on Lipid Metabolism- (미강(米糠)과 야채첨가식이(野菜添加食餌)가 흰쥐의 체내대사(體內代謝)에 미치는 영향(影響) (III) -지방대사에 미치는 영향을 중심으로-)

  • Yu, Choon-Hie;Kim, Sook-He
    • Journal of Nutrition and Health
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    • v.10 no.3
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    • pp.25-32
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    • 1977
  • The effects of dietary cellulose on the lipid metabolism in albino rats were observed, especially the effects of dietary cellulose from three different sources; cereal, vegetable and pure-cellulose. The results were summarized as follows. 1. Dietary cellulose from rice bran and vegetable resulted in lowering of reserved lipid in the body and the effect of rice bran was remarkable as compare to that of vegetable. 2. But the fatty acids composition in serum, liver, gastrocnemius, small intestine and epididymal fat pad was unchanged by dietary cellulose. This means the effect of dietary cellulose was only to change the body fat in quantify and not in quality. 3. Cellulose from rice bran increased serum cholesterol content and maintained medium level of serum total lipid. Cellulose from vegetable decreased serum total lipid and cholesterol content. Pure-cellulose decreased also serum total lipid and cholesterol content but the effect was not as low as vegetable cellulose. 4. It need to be further investigated on the different effects of cellulose from three sources on serum cholesterol content, particularly the increasing effects of rice bran.

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Latilactobacillus sakei WIKIM31 Decelerates Weight Gain in High-Fat Diet-Induced Obese Mice by Modulating Lipid Metabolism and Suppressing Inflammation

  • Park, Sung-Soo;Lim, Seul Ki;Lee, Jieun;Park, Hyo Kyeong;Kwon, Min-Sung;Yun, Misun;Kim, Namhee;Oh, Young Joon;Choi, Hak-Jong
    • Journal of Microbiology and Biotechnology
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    • v.31 no.11
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    • pp.1568-1575
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    • 2021
  • Obesity and related metabolic diseases are major problems worldwide. Some probiotics are currently considered potential therapeutic strategies for obesity. We aimed to investigate the anti-obesity efficacy of Latilactobacillus sakei WIKIM31 in obese mice induced by a high fat diet. The administration of a high-fat diet with L. sakei WIKIM31 reduced body weight gain, epididymal fat mass, triglyceride and total cholesterol levels in the blood, and remarkably decreased the expression of lipogenesis-related genes in the epididymal adipose tissue and liver. Interestingly, intake of L. sakei WIKIM31 improved gut barrier function by increasing the gene expression of tight junction proteins and suppressing the inflammatory responses. Additionally, L. sakei WIKIM31 enhanced the production of short-chain fatty acids, such as butyrate and propionate, in the intestinal tract. These results showed that L. sakei WIKIM31 can be used as a potential therapeutic probiotic for obesity.