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1
Eaton, Simon. "Regulation of fatty acid #beta#-oxidation." Thesis, University of Newcastle Upon Tyne, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311443.
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Spurway, Tracy Deborah. "Control of hepatic fatty acid oxidation." Thesis, University of Newcastle Upon Tyne, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283671.
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Jackson, Sandra. "Enzymes of mitochondrial fatty acid oxidation." Thesis, University of Newcastle Upon Tyne, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283069.
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Smith, Simon. "Polyunsaturated fatty acid oxidation in Alzheimer’s disease." Thesis, Aston University, 2011. http://publications.aston.ac.uk/16499/.
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Alzheimer’s disease is a neurodegenerative disorder which has been characterised with genetic (apolipoproteins), protein (ß-amyloid and tau) and lipid oxidation/metabolism alterations in its pathogenesis. In conjunction with the Dementia Research Group, Bristol University, investigation into genetic, protein and lipid oxidation in Alzheimer’s disease was conducted. A large sample cohort using the double-blind criteria, along with various clinical and chemical data sets were used to improve the statistical analysis and therefore the strength of this particular study. Bristol University completed genetic and protein analysis with lipid oxidation assays performed at Aston University. Lipid oxidation is a complex process that creates various biomarkers, from transient intermediates, to short carbon chain products and cyclic ring structures. Quantification of these products was performed on lipid extracts of donated clinical diseased and non-diseased frontal and temporal brain regions, from the Brain Bank within Frenchay Hospital. The initial unoxidised fatty acids, first transient oxidation intermediates the conjugated dienes and lipid hydroperoxides, the endpoint aldehyde biomarkers and finally the cyclic isoprostanes and neuroprostanes were determined to investigate lipid oxidation in Alzheimer’s. Antioxidant levels were also investigated to observe the effect of oxidation on the defence pathways. Assays utilised in this analysis included; fatty acid composition by GC-FID, conjugated diene levels by HPLC-UV and UV-spec, lipid hydroperoxide levels by FOX, aldehyde content by TBARs, antioxidant status by TEAC and finally isoprostane and neuroprostane quantification using a newly developed EI-MS method. This method involved the SIM of specific ions from F-ring isoprostane and neuroprostane fragmentation, which enabled EI-MS to be used for their quantification. Analyses demonstrated that there was no significant difference between control and Alzheimer samples across all the oxidation biomarkers for both brain regions. Antioxidants were the only marker that showed a clear variance; with Alzheimer samples having higher levels than the age matched controls. This unique finding is supported with the observed lower levels of lipid oxidation biomarkers in Alzheimer brain region samples. The increased antioxidant levels indicate protection against oxidation which may be a host response to counteract the oxidative pathways, but this requires further investigation. In terms of lipid oxidation, no definitive markers or target site for therapeutic intervention have been revealed. This study concludes that dietary supplementation of omega-3 fatty acids or antioxidants would most likely be ineffective against Alzheimer disease, although it may support improvement in other areas of general health.
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Rocha, Hugo Daniel Carvalho de Azevedo. "Mitochondrial dysfunction in fatty acid β-oxidation disorders." Doctoral thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14297.
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Doutoramento em BioquímicaMitochondria are central organelles for cell survival with particular relevance in energy production and signalling, being mitochondrial fatty acid β–oxidation (FAO) one of the metabolic pathways harboured in this organelle. FAO disorders (FAOD) are among the most well studied inborn errors of metabolism, mainly due to their impact in health. Nevertheless, some questions remain unsolved, as their prevalence in certain European regions and how pathophysiological determinants combine towards the phenotype. Analysis of data from newborn screening programs from Portugal and Spain allowed the estimation of the birth prevalence of FAOD revealing that this group of disorders presents in Iberia (and particularly in Portugal) one of the highest European birth prevalence, mainly due to the high birth prevalence of medium chain acyl-CoA dehydrogenase deficiency. These results highlight the impact of this group of genetic disorders in this European region. The characterization of mitochondrial proteome, from patients fibroblasts with FAOD, namely multiple acyl-CoA dehydrogenase deficiency (MADD) and long chain acyl-CoA dehydrogenase deficiency (LCHADD), provided a global perspective of the mitochondrial proteome plasticity in these disorders and highlights the main molecular pathways involved in their pathogenesis. Severe MADD forms show an overexpression of chaperones, antioxidant enzymes (MnSOD), and apoptotic proteins. An overexpression of glycolytic enzymes, which reflects cellular adaptation to energy deficiency due to FAO blockage, was also observed. When LCHADD fibroblasts were analysed a metabolic switching to glycolysis was also observed with overexpression of apoptotic proteins and modulation of the antioxidant defence system. Severe LCHADD present increased ROS alongside with up regulation of MnSOD while moderate forms have lower ROS and down-regulation of MnSOD. This probably reflects the role of MnSOD in buffering cellular ROS, maintain them at levels that allow cells to avoid damage and start a cellular response towards survival. When ROS levels are very high cells have to overexpress MnSOD for detoxifying proposes. When severe forms of MADD were compared to moderate forms no major differences were noticed, most probably because ROS levels in moderate MADD are high enough to trigger a response similar to that observed in severe forms. Our data highlights, for the first time, the differences in the modulation of antioxidant defence among FAOD spectrum. Overall, the data reveals the main pathways modulated in FAOD and the importance of ROS levels and antioxidant defence system modulation for disease severity. These results highlight the complex interaction between phenotypic determinants in FAOD that include genetic, epigenetic and environmental factors. The development of future better treatment approaches is dependent on the knowledge on how all these determinants interact towards phenotype.!
A mitocôndria desempenha um papel fundamental na regulação de vários processos celulares, com particular relevância na produção de energia, sendo a β-oxidação mitocondrial dos ácidos gordos uma das vias metabólicas que tem lugar neste organelo. Os défices da β-oxidação mitocondrial dos ácidos gordos estão entre os grupos de doenças metabólicas mais estudados, existindo contudo, algumas questões que continuam por esclarecer, como a sua prevalência ao nascimento em determinadas regiões da Europa e quais e de que forma os vários determinantes patofisiológicos interatuam para produzir um determinado fenótipo. A análise dos dados de programas de rastreio neonatal da península Ibérica possibilitou estimar a prevalência ao nascimento dos défices da β-oxidação mitocondrial, tendo-se observado um dos valores mais elevados (particularmente em Portugal) no âmbito das regiões europeias, fundamentalmente devido à grande prevalência ao nascimento dos défices da desidrogenase dos ácidos gordos de cadeia média. Estes resultados realçam o impacto deste grupo de doenças genéticas nesta região europeia. A caracterização do proteoma mitocondrial, a partir de fibroblastos em cultura, de doentes com défices da β-oxidação mitocondrial (especificamente défice múltiplo das desidogenases (MADD) e défice da desidrogenase dos ácidos 3- hidroxilados de cadeia longa (LCHADD)) permitiu obter uma perspetiva geral sobre a plasticidade do proteoma mitocondrial nestas doenças assim como avaliar quais as principais vias metabólicas envolvidas na sua patogénese. Em formas severas de MADD foi observada uma sobre-expressão de chaperones, enzimas antioxidantes e proteínas associadas à apoptose. Nestas células foi igualmente observada a sobre-expressão de enzimas glicolíticas, como adaptação ao bloqueio da β-oxidação. A análise de amostras de doentes com LCHADD também evidenciou uma sobre-expressão de enzimas glicolíticas, assim como de proteínas relacionadas com a apoptose, e a modulação do sistema de defesa antioxidante. O doente com uma forma severa de LCHADD apresentou níveis de stress oxidativo elevados, associados a uma sobre expressão da MnSOD, enquanto o doente com uma forma moderada apresentou níveis mais baixos de stress oxidativo e uma sub-expressão da MnSOD. Estes resultados são provavelmente o reflexo do papel da MnSOD na regulação dos níveis de ROS, mantendo-os em níveis que não provoquem danos, mas que permitam iniciar processos de sinalização com vista à manutenção celular. A comparação de forma moderadas com severas de MADD não revelou diferenças significativas, muito provavelmente porque os níveis de stress oxidativo são suficientemente altos para despoletar uma resposta semelhante às formas severas. Os presentes resultados realçam as diferenças na modulação do sistema de defesa antioxidante no espectro dos défices da β-oxidação mitocondrial. No seu conjunto os resultados obtidos revelam as principais vias moduladas nos défices da β-oxidação mitocondrial e a importância do stress oxidativo e sistema de defesa antioxidante para o fenótipo. Ao permitem compreender melhor a complexa interação entre os vários fatores que interagem com vista ao fenótipo e que podem ser de origem genética, epigenética ou ambiental, contribuem para o desenvolvimento de novas e mais eficazes abordagens terapêuticas.
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Wang, Wenzhong. "Mechanistic studies of flavoenzymes in fatty acid oxidation and oxidative protein folding." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 233 p, 2007. http://proquest.umi.com/pqdweb?did=1362529911&sid=3&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Taylor, George. "Fatty acid metabolism in cyanobacteria." Thesis, University of Exeter, 2012. http://hdl.handle.net/10871/9363.
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With crude oil demand rising and supplies being depleted, alternative energy, specifically biofuels, are of intense scientific interest. Current plant crop based biofuels suffer from several problems, most importantly the use of land needed for food. Cyanobacteria offer a solution to this problem as they do not compete with land for food and produce hydrocarbons that can be used as biofuels. Upon examination of metabolic pathways competing with hydrocarbon synthesis, it appeared that cyanobacteria lacked the major fatty acid degradative metabolic pathway β-oxidation, generally thought to be a universally occurring pathway. Lack of this pathway in cyanobacteria was confirmed by employing a range of analytical techniques. Bioinformatic analysis suggested that potential enzymes with β-oxidation activity were involved in other metabolic pathways. A sensitive assay was set up to detect acyl- CoAs, the substrates of β-oxidation, using liquid chromatography triple quadrupole mass spectrometry. None could be detected in cyanobacteria. No enzymatic activity from the rate-limiting acyl-CoA dehydrogenase/oxidase could be detected in cyanobacterial extracts. It was found that radiolabeled fatty acids fed to cyanobacteria were utilised for lipid membranes as opposed to being converted to CO2 by respiration or into other compounds by the TCA cycle. An element of the β-oxidation pathway, E. coli acyl-CoA synthetase was ectopically expressed in a strain of cyanobacteria and implications of the introduction of acyl-CoA synthesis were assessed. Finally, the regulation of the fatty acid biosynthetic pathway was investigated. It was determined that under conditions of excess fatty acid, the transcription of acetyl-CoA carboxylase and enoyl-ACP reductase was repressed and acyl-ACP synthetase involved in fatty acid recycling was induced. These results were discussed in relation to fatty acid oxidation and hydrocarbon biosynthesis in other organisms.
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Mansouri, Abdelhak. "Hepatic fatty acid oxidation and control of food intake /." Zürich : ETH, 2008. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17697.
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New, Karen Jayne. "Control of hepatic fatty acid oxidation in suckling rats." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392103.
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Bacher, Mohamed A. "Induction of microsomal and peroxisomal fatty acid oxidation by chlorophenoxy acid herbicides." Thesis, University of Surrey, 1989. http://epubs.surrey.ac.uk/847223/.
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Induction of the cytochrome P-450 mixed-function oxidase and specifically the cytochrome P-450 IVA1 isoenzyme by seven phenoxy acid herbicides in rat liver and kidney, have been studied. results using liver microsomes demonstrated that the 12-hydroxylation of lauric acid was significantly induced by all compounds (3-8-fold), 4-chlorophenoxyacetic acid (CPA) (300 mg/kg) being the weakest and 2,4,5-trichlorophenoxypropionic acid (2,4,5-TP) (200 mg/kg) the most potent inducers respectively. This increase in lauric acid 12-hydroxylase-activity was accompanied by an increase in the hepatic content of cytochrome P-450 IVA1 as assessed by both a qualitative Western blot procedure and a quantitative ELISA method. Furthermore, there was a parallel increase in cytochrome P-450 IVA1 mRNA and a similar increase in peroxisomal B-oxidation subsequent to exposure to these compounds. In addition, benzphetamine-N-demethylase, a marker of cytochrome P-450 IIBl and IIB2 activities, was not affected by any of the herbicides, whereas cytochrome P-450 IA1 and IA2, as assayed by ethoxyresorufin-O-deethylase activity, was significantly increased (up to 2.2-fold) by some of the compounds. Kidney microsomal parameters were not affected by any of these compounds. My in vivo studies using antipyrine, pentobarbital and zoxazolamine indicated that the metabolism of these substrates was marginally affected by only some of the compounds. In order to highlight the possible involvement of a metabolite of the chlorophenoxy acids in the induction of cytochrome P-450, I investigated four related chlorophenols. There was no significant change in cytochrome P-450 isoenzyme levels in rat liver and kidney microsomes nor was there any increase in peroxisomal beta-oxidation. Taken collectively, the results presented in this thesis indicate that the chlorinated phenoxy acid herbicides studied preferentially induce the cytochrome P-450 IVA1 isoenzyme and peroxisomal beta-oxidation in a pattern similar to the typical inducers of this isoenzyme such as clofibrate. A scheme is presented whereby induction of catalytically competent cytochrome P-450 IVA1 is required for the phenomenon of peroxisome proliferation by these chlorophenoxy acid derivatives.
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Smith, E. H. "The enzymic oxidation of linoleic and linolenic acid." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380185.
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Makinde, Abiola Olufemi. "Maturation of fatty acid oxidation in the newborn rabbit heart." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0004/NQ39561.pdf.
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Watmough, N. J. "Measurement of intermediates and products of fatty acid #beta#-oxidation." Thesis, University of Newcastle Upon Tyne, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234411.
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Gu, Lei. "Potential of Anaplerotic Triheptanoin for the Treatment of Long-chain Fatty Acid Oxidation Disorders." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1263926817.
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Djian, Benjamin. "Fatty acid oxidizing enzymes in Lobosphaera incisa." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2017. http://hdl.handle.net/11858/00-1735-0000-002E-E3C2-6.
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Adhikari, Sean. "Glucose oxidation in heart-type fatty acid binding protein null mice." Texas A&M University, 2006. http://hdl.handle.net/1969.1/4391.
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Heart-type fatty acid binding protein (H-FABP) is a major fatty acid binding
factor in skeletal muscles. Genetic lack of H-FABP severely impairs the esterification
and oxidation of exogenous fatty acids in soleus muscles isolated from chow-fed mice
(CHOW-solei) and high fat diet-fed mice (HFD-solei), and prevents the HFD-induced
accumulation of muscle triglycerides. Here, we examined the impact of H-FABP
deficiency on the relationship between fatty acid utilization and glucose oxidation.
Glucose oxidation was measured in isolated soleus muscles in the presence or absence of
1 mM palmitate (simple protocol) or in the absence of fatty acid after preincubation with
1 mM palmitate (complex protocol). With the simple protocol, the mutation slightly
reduced glucose oxidation in CHOW-muscles, but markedly increased it in HFDmuscles;
unexpectedly, this pattern was not altered by the addition of palmitate, which
reduced glucose oxidation in both CHOW- and HFD-solei irrespective of the mutation. In
the complex protocol, the mutation first inhibited the synthesis and accumulation of
triglycerides and then their mobilization; with this protocol, the mutation increased
glucose oxidation in both CHOW- and HFD-solei. We conclude: (i) H-FABP mediates a
non-acute inhibition of muscle glucose oxidation by fatty acids, likely by enabling both
the accumulation and mobilidoes not mediate the acute inhibitory effect of extracellular fatty acids on muscle glucose
oxidation; (iii) H-FABP affects muscle glucose oxidation in opposing ways, with
inhibition prevailing at high muscle triglyceride contents.zation of a critical mass of muscle triglycerides; (ii) H-FABP
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Surina-Baumgartner, Denise M. "Fatty acid oxidation and insulin in the control of food intake /." [S.l.] : [s.n.], 1995. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=11083.
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Grunsven, Elisabeth Gerarda van. "Functions and dysfunctions of peroxisomal fatty acid [beta]-oxidation in man." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/82102.
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Mels, Catharina Martha Cornelia. "The assessment of detoxification metabolism in fatty acid oxidation deficiencies / C.M.C. Mels." Thesis, North-West University, 2010. http://hdl.handle.net/10394/4406.
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The concept of accumulating xenobiotics within the human body as a health risk is well known. However, these compounds can also be endogenous, as in the case of inborn errors of metabolism. Biotransformation of both exogenous and endogenous toxic compounds is an important function of the liver, and the critical balance between these systems is of fundamental importance for cellular health. Fatty acid ?-oxidation deficiencies are associated with characteristic clinical symptoms as a consequence of the accumulation of specific metabolites. For these accumulated metabolites various nutrients are indispensable for optimal biotransformation and continuous accumulation of metabolites can ultimately result in the depletion of biotransformation substrates and cofactors.
In this study, a novel model (the unbalanced biotransformation metabolism model) is proposed that describes the critical balance between Phase I and Phase II biotransformation and how a disturbance in this balance will increase the oxidative stress status. The significance of this model lies within the treatment possibilities, as the assessment of biotransformation metabolism and oxidative stress status can lead to the development of nutritional treatment strategies to correct imbalances. The value of this model is illustrated by its application to a clinical case investigated.
In addition to the use of nutritional supplementation in treatment, biotransformation substrates and cofactors were also used to develop a ?substrate loading cocktail?. This cocktail ensured sufficient availability of biotransformation substrates and precursors to stimulate coenzyme A biosynthesis. The application of this ?substrate loading cocktail? in subjects with both induced and inborn errors in fatty acid oxidation demonstrated that such a novel approach is a useful tool to give new insight into these kinds of deficiencies and open the possibility for the identification of new deficiencies.
Interesting observations made in subjects originally referred for biotransformation and oxidative stress status profiles led to the first in vivo evidence of an inhibitory effect of acetylsalicylic acid on short-chain fatty acid metabolism possibly at the level of isobutyryl-CoA dehydrogenase. Since not all individuals were affected to the same degree, this observation can potentially be used to detect individuals with rate-limiting polymorphisms or mutations in the isobutyryl-CoA dehydrogenase enzyme.Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2011.
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Gonzalez, Sonia. "Oxidation and Textural Characteristics of Butter and Ice Cream with Modified Fatty Acid Profiles." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/34076.
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Milk fat composition determines specific rheological, sensory and physicochemical properties of dairy products such as texture, melting point, flavor, color, oxidation rates, and viscosity. Previous studies have shown that milkfats containing higher levels of long chain polyunsaturated fatty acids have lower melting points and decreased solid fat contents which leads to softer-textured products. An increased risk of higher oxidation rates can be a disadvantage of high levels of polyunsaturated fatty acids.
Three different milkfat compositions were obtained through dietary manipulation of cows: high oleic content, high linoleic content and control milkfat. Ice cream and butter were processed from the treated and control milks. Butter and ice cream samples then were analyzed to measure differences in fatty acid profiles and firmness. High-oleic and high-linoleic milkfat had lower concentrations of saturated fatty acids, such as C 16:0. Conjugated linoleic acid content was increased in the high-linoleic milkfat. High-oleic milkfat resulted in a softer butter. Ice cream samples were analyzed to measure differences in viscosity, melting point, oxidation rate and sensory perception. Significant differences (P<0.05) were found in the fatty acid profiles of milkfat, ice cream mix viscosity, peroxide values of ice cream after 3 to 5 months of storage, butter color, and butter firmness. Sensory analyses included a scooping test at -18°C to detect differences in texture. A difference test was conducted to determine oxidation flavor differences between the three ice cream treatments at extended storage times. No significant differences were found in the scooping test or the oxidation flavor difference.
Manipulation of the cow's diet increased the total amount of unsaturated fatty acids. It also influenced firmness of butter and behavior of peroxide values during extended storage of high-linoleic ice cream.Master of Science
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Sim, Keow Giak. "Quantitative Fibroblast Acylcarnitine Profiling In The Diagnostic and Prognostic Assessment of Mitochondrial Fatty Acid �-Oxidation Disorders." University of Sydney. Paediatrics and Child Health, 2002. http://hdl.handle.net/2123/801.
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Mitochondrial fatty acid �-oxidation disorders are a group of clinically and biochemically heterogeneous defects mainly associated with intolerance to catabolic stress. The diseases are potentially fatal, but treatable and the prognosis for most diagnosed disorders is generally favourable. Early diagnosis is thus important to prevent morbidity and mortality. This project describes an improved and validated quantitative fibroblast acylcarnitine profile assay for the investigation of suspected fatty acid �-oxidation disorders. Intact cells were incubated with deuterium-labelled hexadecanoate and L-carnitine, and the accumulated acylcarnitines in the medium analysed using electrospray tandem mass spectrometry. This modified procedure is less demanding technically, requires fewer cells and better reflects the in vivo acylcarnitine status than previously published methods. Mitochondrial fatty acid �-oxidation is coupled to the respiratory chain. Functional defects of one pathway may lead to secondary alterations in flux through the other. The diagnostic specificity and the prognostic potential of the in vitro acylcarnitine profile assay were investigated in fibroblasts from 14 normal controls, 38 patients with eight enzyme deficiencies of fatty acid �-oxidation presenting with various phenotypes, and 16 patients with primary respiratory chain defects including both isolated and multiple enzyme complex defects. All fatty acid �-oxidation deficient cell lines revealed disease-specific acylcarnitine profiles related to the sites of defects irrespective of the severity of symptoms or of different mutation. Preliminary studies suggested a correlation between severity of symptoms and higher concentrations of long-chain acylcarnitine species. However, the fibroblast acylcarnitine profiles from some patients with respiratory chain defects were similar to those of controls, whereas others had abnormal profiles resembling those found in fatty acid �-oxidation disorders. In vitro acylcarnitine profiling is useful for the detection of fatty acid �-oxidation deficiencies, and perhaps the prediction of disease severity and prognostic evaluation facilitating decisions of therapeutic intervention and genetic counselling. However, abnormal profiles do not exclusively indicate these disorders, and primary defects of the respiratory chain remain a possibility. Awareness of this diagnostic pitfall will aid in the selection of subsequent confirmatory tests and therapeutic options.
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Fujikawa, Teppei. "Study on the regulation of fatty acid oxidation by central nervous system." Kyoto University, 2008. http://hdl.handle.net/2433/136596.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第13869号
農博第1684号
新制||農||953(附属図書館)
学位論文||H20||N4336(農学部図書室)
UT51-2008-C785
京都大学大学院農学研究科食品生物科学専攻
(主査)教授 伏木 亨, 教授 井上 國世, 教授 河田 照雄
学位規則第4条第1項該当
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Derrick, Jeremy Paul. "L-carnitine palmitoyltransferases." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293503.
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Portolesi, Roxanne, and roxanne portolesi@flinders edu au. "Fatty acid metabolism in HepG2 cells: Limitations in the accumulation of docosahexaenoic acid in cell membranes." Flinders University. Medicine, 2007. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20070802.103146.
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The current dietary recommendations for optimal health are designed to increase our intake of two bioactive omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), abundant naturally in fatty fish such as salmon. Health authorities recommend that the general population consume two to three fatty fish meals per week (1) for optimal health and for the prevention of cardiovascular disease. However, some modern Western societies consume only modest amounts of fish and seafood (2;3). Land based vegetable oils may provide an alternative to meet these needs. Linseed and canola oils are rich in alpha-linolenic acid (ALA, 18:3n-3) (4). ALA can be converted endogenously to EPA and DHA and suggests that increasing the dietary intake of ALA may increase the conversion and accumulation of DHA in tissues and plasma. However, elevated dietary intakes of ALA in animals and humans results in an increased level of EPA in tissues yet there is little or no change in the level of DHA (5-7). The current consensus is that the synthesis of DHA from ALA in humans is limited yet the mechanisms involved in regulating the accumulation of DHA in tissues are poorly understood.
The reputed rate-limiting enzyme in the conversion of fatty acids is delta 6 desaturase (D6D). ALA is a substrate for D6D and undergoes a series of desaturation and elongation reactions to yield n-3 long chain polyunsaturated fatty acids (LCPUFA). The final step in the synthesis of DHA from ALA involves translocation of its immediate fatty acid precursor, 24:6n-3 from the endoplasmic reticulum to the peroxisome to be partially beta-oxidised to yield DHA. The involvement of multiple enzymes in the desaturation-elongation pathway, and the integration of other pathways, such as phospholipid biosynthesis, suggests there are various steps that may regulate the accumulation of DHA in cell membranes. This thesis aimed to examine the possible regulatory steps in the conversion of fatty acids to LCPUFA, particularly in the synthesis of DHA from n-3 fatty acid precursors.
The human hepatoma cell line, HepG2, was used as an in vitro cell system to examine the accumulation of individual fatty acids and their metabolites in isolation from other competing fatty acid substrates. The accumulation of linoleic acid (LA, 18:2n-6) and ALA in HepG2 cell phospholipids following supplementation with increasing concentrations of each respective fatty acid correlated with that described in vivo, as was the accumulation of their conversion products. The accumulation of DHA in cells supplemented with ALA reached a plateau at concentrations above 5 micro g/ml and paralleled the accumulation of 24:6n-3 in cell phospholipids, suggesting that the delta 6 desaturation of 24:6n-3 was prevented by increasing concentrations of ALA, thereby limiting the accumulation of DHA. The accumulation of DHA in cells supplemented with eicosapentaenoic acid (EPA, 20:5n-3) or docosapentaenoic acid (DPA, 22:5n-3) was significantly greater than the level of DHA that accumulated in cells supplemented with ALA. However, regardless of substrate, the level of DHA in cell membranes reached a plateau at substrate concentrations above 5 micro g/ml.
This thesis further aimed to examine the effect of fatty acid supplementation on the mRNA expression of D6D in HepG2 cells. The expression and activity of D6D mRNA is subject to nutritional and hormonal regulation. The mRNA expression of D6D in HepG2 cells following supplementation with oleic acid (OA, 18:1n-9), LA, ALA, arachidonic acid (AA, 20:4n-6) or EPA was examined by real time RT PCR. The expression of D6D mRNA was reduced by up to 50% in cells supplemented with OA, LA, ALA , AA or EPA compared with control cells and suggests that fatty acids modulate the expression of the key enzyme involved in the conversion of fatty acids.
The effect of fatty acid co-supplementation on the fatty acid composition of HepG2 cell phospholipids was also examined in an attempt to gain insights into the role of D6D and the enzymes involved in peroxisomal beta-oxidation on the accumulation of DHA from n-3 fatty acid precursors. The reduction in the accumulation of DHA in cells co-supplemented with DPA and docosatetraenoic acid (DTA, 22:4n-6) was greater than in cells co-supplemented with DPA and LA, suggesting that peroxisomal beta-oxidation may have a greater role in determining the accumulation of DHA from DPA than the activity of D6D. Further investigation should be directed towards understanding the role that peroxisomal beta-oxidation may play in the synthesis of DHA from precursor fatty acids.
The fatty acid composition of cell membranes in vivo is a result of several physiological processes including dietary intake, phospholipids biosynthesis and fatty acid conversion as well as catabolic processes. This thesis demonstrates that a greater understanding of the regulation of the conversion of fatty acids will help to define dietary approaches that enhance the synthesis of n-3 LCPUFA from n-3 fatty acid precursors to lead to improved outcomes for health.
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Adamek, Gaston. "Fatty acid oxidation in bone tissue and bone cells : characterization and hormonal influences /." [S.l : s.n.], 1987. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Jenkins, Benjamin John. "The role of alpha oxidation in lipid metabolism." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/278025.
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Recent findings have shown an inverse association between the circulating levels of pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) with the risk of pathological development in type 2 diabetes, cardio vascular disease and neurological disorders. From previously published research, it has been said that both these odd chain fatty acids are biomarkers of their dietary intake and are significantly correlated to dietary ruminant fat intake. However, there are profound studies that show the contrary where they do not display this biomarker correlation. Additionally, several astute studies have suggested or shown odd chain fatty acid endogenous biosynthesis, most often suggested via alpha oxidation; the cleavage of a single carbon unit from a fatty acid chain within the peroxisomes. To better understand the correlations and interactions between these two fatty acids with pathological development, the origin of these odd chain fatty acids needed to be determined, along with confirming their association with the disease aetiology. To minimise animal & human experimentation we made use of existing sample sets made available through institutional collaborations, which produced both animal and human interventional study samples suitable for odd chain fatty acid investigations. These sample collaborations allowed us to comprehensively investigate all plausible contributory sources of these odd chain fatty acids; including from the intestinal microbiota, from dietary contributions, and derived from novel endogenous biosynthesis. The investigations included two intestinal germ-free studies, two ruminant fat diet studies, two dietary fat studies and an ethanol intake study. Endogenous biosynthesis was assessed through: a stearic acid infusion, phytol supplementation, and an Hacl1 knockout mouse model. A human dietary intervention study was used to translate the results. Finally, a study comparing circulating baseline C15:0 and C17:0 levels with the development of glucose intolerance. We found that the circulating C15:0 and C17:0 levels were not significantly influenced by the presence or absence of intestinal microbiota. The circulating C15:0 levels were significantly and linearly increased when the C15:0 dietary composition increased; however, there was no significant correlation in the circulating C17:0 levels with intake. Circulating levels of C15:0 were affected by the dietary composition and factors affecting the dietary intake, e.g. total fat intake and ethanol, whereas circulating C17:0 levels were found to be independent of these variables. In our studies, the circulating C15:0 levels were not significantly affected by any expected variations in alpha oxidation caused by pathway substrate inhibition or gene knockout. However, C17:0 was significantly related, demonstrating it is substantially endogenously biosynthesised. Furthermore, we found that the circulating C15:0 levels, when independent of any dietary variations, did not correlate with the progression of glucose intolerance when induced, but the circulating C17:0 levels did significantly relate and linearly correlated with the development of glucose intolerance. To summarise, the circulating C15:0 and C17:0 levels were independently derived; the C15:0 levels substantially correlated with its dietary intake, whilst the C17:0 levels proved to be separately derived from its endogenous biosynthesis via alpha oxidation of stearic acid. C15:0 was found to be minimally endogenously biosynthesised via a single cycle of beta oxidation of C17:0 in the peroxisomes, however, this did not significantly contribute to the circulating levels of C15:0. Additionally, only the baseline levels of C17:0 significantly correlated with the development of glucose intolerance. These findings highlight the considerable differences between both of these odd chain fatty acids that were once thought to be homogeneous and similarly derived. On the contrary, they display profound dietary, metabolic, and pathological differences.
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Furumoto, Hidehiro. "Studies on Nutraceutical Properties of Modified Fatty Acids by Autoxidation and Lactic Acid Bacterial Metabolism." Kyoto University, 2016. http://hdl.handle.net/2433/215592.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第19766号
農博第2162号
新制||農||1040(附属図書館)
学位論文||H28||N4982(農学部図書室)
32802
京都大学大学院農学研究科応用生物科学専攻
(主査)教授 菅原 達也, 教授 澤山 茂樹, 教授 佐藤 健司
学位規則第4条第1項該当
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Qin, Y. M. (Yong-Mei). "Molecular characterization of peroxisomal multifunctional 2-enoyl-CoA hydratase 2/(3R)-hydroxyacyl-CoA dehydrogenase (MFE type 2) from mammals and yeast." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:951425337X.
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Abstract
Fatty acid degradation in living organisms occurs mainly via the β-oxidation pathway. When this work was started, it was known that the hydration and dehydrogenation reactions in mammalian peroxisomal β-oxidation were catalyzed by only multifunctional enzyme type 1 (MFE-1; Δ2-Δ3-enoyl-CoA isomerase/2-enoyl-CoA hydratase 1/(3S)-hydroxyacyl-CoA dehydrogenase) via the S-specific pathway, whereas in the yeast peroxisomes via the R-specific pathway by multifunctional enzyme type 2 (MFE-2; 2-enoyl-CoA hydratase 2/(3R)-hydroxyacyl-CoA dehydrogenase).
The work started with the molecular cloning of the rat 2-enoy-CoA hydratase 2 (hydratase 2). The isolated cDNA (2205 bp) encodes a polypeptide with a predicted molecular mass of 79.3 kDa, which contains a potential peroxisomal targeting signal (AKL) in the carboxyl terminus. The hydratase 2 is an integral part of the cloned polypeptide, which is assigned to be a novel mammalian peroxisomal MFE-2.
The physiological role of the mammalian hydratase 2 was investigated with the recombinant hydratase 2 domain derived from rat MFE-2. The protein hydrates a physiological intermediate (24E)-3α, 7α, 12α-trihydroxy-5β-cholest-24-enoyl-CoA to (24R, 25R)-3α, 7α, 12α, 24-tetrahydroxy-5β-cholestanoyl-CoA in bile acid synthesis.
The sequence alignment of human MFE-2 with MFE-2(s) of different species reveals 12 conserved protic amino acid residues, which are potential candidates for catalysis of the hydratase 2. Each of these residues was replaced by alanine. Complementation of Saccharomyces cerevisiae fox-2 (devoid of endogenous MFE-2) with human MFE-2 provided a model system for examing the in vivo function of the variants. Two protic residues, Glu366 and Asp510, of the hydratase 2 domain of human MFE-2 have been identified and are proposed to act as a base and an acid in catalysis.
Mammalian MFE-2 has a (3R)-hydroxyacyl-CoA dehydrogenase domain, whereas the yeast MFE-2 has two dehydrogenase domains, A and B. The present work, applying site-directed mutagenesis to dissect the two domains, shows that the growth rates of fox-2 cells expressing a single functional domain are lower than those of cells expressing S. cerevisiae MFE-2. Kinetic experiments with the purified proteins demonstrate that domain A is more active than domain B in catalysis of medium- and long-chain (3R)-hydroxyacyl-CoA, whereas domain B is solely responsible for metabolism of short-chain substrates. Both domains are required when yeast cells utilize fatty acids as the carbon source.
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Chae, Sung Hee. "Conjugated linoleic acid reduces lipid oxidation in irradiated, cooked ground beef patties." Diss., Texas A&M University, 2005. http://hdl.handle.net/1969.1/5983.
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This study was conducted to examine the antioxidative effect of conjugated linoleic acid (CLA) in irradiated, cooked ground beef patties. The hypothesis was that CLA would be retained during irradiation and would reduce lipid oxidation that is caused by irradiation. The objective was to evaluate the effects of CLA alone and in combination with irradiation on lipid oxidation, fatty acid composition, cooking loss, moisture and fat content, and trained panel sensory evaluations of beef patties. CLA was added at 0, 1, 2, or 4% level during the grinding process. Addition of CLA during the grinding process increased CLA cis-9,trans-11 and CLA trans-10,cis-12 isomers in both irradiated and non-irradiated cooked ground beef patties (irradiated at 1.6 kGy) (P = 0.0001). Weight loss during cooking was greater in irradiated beef patties than in non-irradiated patties (P = 0.004). Irradiation reduced the serumy/bloody aromatic attribute and increased browned aromatic attribute, browned aftertaste, and wet dog/hairy aromatic attribute (P < 0.05). There was no significant main effect of irradiation on the basic tastes. The linoleic acid, CLA cis-9,trans-11, and CLA trans-10,cis-12 were decreased by irradiation (P < 0.05). Although irradiation decreased the CLA isomers, higher percentages of CLA isomers were retained in irradiated patties containing a 4% free fatty acid preparation of CLA (FFA-CLA), reflecting the ability of the FFA preparation to reduce lipid oxidation that is caused by irradiation. The thiobarbituric acid reactive substances (TBARS) values were significantly higher in irradiated, cooked ground beef patties than in non-irradiated ground beef patties (P = 0.004). Although the FFA-CLA was effective in reducing lipid oxidation that is caused by irradiation, it increased painty aromatic attribute, bitter taste, and astringent aftertaste due to the soapy flavor of the free fatty acid (all P < 0.05). The FFA-CLA decreased cooked beef/brothy and serumy/bloody aromatic attribute and browned aftertaste (all P < 0.05). The 1% triacylglycerol (TAG) preparation of CLA reduced TBARS in irradiated, cooked patties to levels seen in control, non-irradiated patties. The 1% TAG concentration also provided good retention of CLA in the cooked ground beef.
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Stroup, Laurie B. "Radioactive pyruvate oxidation and the effects of fatty acid inhibition in the aging rat." Virtual Press, 1989. http://liblink.bsu.edu/uhtbin/catkey/560276.
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To investigate the possible changes in pyruvate oxidation during the rapid growth period in an animal model, the oxidation of radioactive labeled pyruvate was measured in mitochondria isolated from the gastrocnemius muscle of Sprague--Dawley rats between 4 and 16 weeks of age. The influence of the fatty acid derivative palmitylcarnitine, as an inhibitor of pyruvate oxidation, was also tested.The gastrocnemius muscle was removed from anesthesized animals at 4, 8 and 16 weeks of age. Isolated mitochondria from the muscle samples were incubated with C1--14C] pyruvate and E1-14C] pyruvate + palmitylcarnitine in a KC1 medium. The decarboxylation of pyruvate was measured by the evolution of radioactive labeled carbon dioxide. Pyruvate oxidation significantly (p .; 0.0001) increased from ages 4 to 16 weeks. The initial low rate of pyruvate oxidation was attributed to the residual metabolic effects of the pre-weaned animal' high-fat diet. The subsequent increase in the capacity of pyruvate oxidation was then explained by the shift in the animaldiet to high-carbohydrate lab chow. These results may also be attributed to the maturation of the hindlimb muscle fibers during this period: the differentiation of predominately red, oxidative fibers to an increase in the percentage of white, glycolytic fibers, common in the adult hindlimb. The fatty acid derivative, palmitylcarnitine, failed to inhibitpyruvate oxidation at the level of decarboxylation. This finding supports the proposal that fatty acids do not inhibit glucose oxidation directly, but instead suppress glycogen breakdown. Thus, the findings indicate an increase in the capacity for- pyruvate oxidation during the rapid growth period without inhibition by the fatty acid derivative, palmitylc_arnitine.Department of Biology
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Roermund, Carolus Wilhelmus Thomas van. "Fatty acid [beta]-oxidation in Saccharomyces cerevisiae new insights with implications for human diseases /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/62779.
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Lee, Sung Jae. "Relationship between Oxidation Reduction Potential (ORP) and Volatile Fatty Acid (VFA) Production in the Acid-Phase Anaerobic Digestion Process." Thesis, University of Canterbury. Civil and Natural Resources Engineering, 2008. http://hdl.handle.net/10092/1262.
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The purpose of this research was to investigate the relationship between the oxidation-reduction potential (ORP) measurement and volatile fatty acid (VFA) production in the acid-phase anaerobic digestion process under different conditions of temperature and residence time. Two identical anaerobic digesters were operated while VFAs, SCOD, VSS, alkalinity, ORP and pH were measured. In digester 1, VFA production of 5,556 mg/L was generated with an ORP of -315 mv at a 10 day SRT; while 5,400 mg/L of VFA with an ORP of -389 mv was recorded in digester 2. The SRT was adjusted at 5, 8, 10, 12 and 15 days and the optimum SRT was 10 days in both digesters. The results of this study indicate there were no tight relationship between VFA production and ORP values, thus ORP by itself is not a good predictor of the amount of VFAs generated. However, ORP combined with temperature had good linear relationship with VFA production. An ORP range of -315 to -390 mv was desirable for maximizing VFA production in both anaerobic digesters. Different temperatures (14, 29 and 37 ℃) were trialed and the results indicate that the conditions at 29 ℃ and 37 ℃ were not significantly different in terms of VFA production, however, less VFAs were generated at the lowest temperature of 14 ℃.
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Li, Qin. "Controlling Light Oxidation Flavor in Omega-3 Fatty Acid Enriched 2% Milk by Packaging Films." Thesis, Virginia Tech, 2011. http://hdl.handle.net/10919/43369.
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Milk is often packaged in translucent containers providing little protection against flavor degradation from light. Addition of omega-3 fatty acid sources into milk increases the risk of light-initiated degradation of nutrients and sensory quality.
The effectiveness of iridescent film materials in reducing light-induced oxidation of extended shelf-life omega-3 fatty acid enriched milk (2% total fat) was studied. Film selections were targeted to provide product visibility and control product exposure at targeted riboflavin excitation wavelength regions. Effectiveness was determined by sensory evaluation and measuring changes in volatile compounds on days 1, 7, 14, and 21 when stored under fluorescent light at 4°C. Five packaging treatments (films overwrapped on glass bottles) were evaluated: 446nm block, 570 nm block, broad spectrum block with 4% transmission (BS4T), light-protected (foil overwrap) control, and light-exposed (no overwrap) control. Experienced panelists (n=12) rated oxidized flavor intensity (0-9; 9=extreme) for milk samples. Light-protected milk was lower in oxidized flavor (mean score less than 3) throughout the storage period. Oxidized flavor in milk with BS4T film overwraps was not different compared to light-protected milk (p>.05) at the later stage (21 days), suggesting some level of protection to milk flavor. Milk without fish oil (milk fat only) shows relatively larger peak areas for 2-butanone on day 14, compared to other milk samples, suggesting antioxidants in the fish oil can prevent light oxidation. Overall, packaging that provides a complete light block is still the best way to prevent light-oxidized flavor in milk.Master of Science in Life Sciences
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Makins, Ronald Allan. "Quantitative analyses of regulation and control of fatty acid oxidation and ketogenesis in liver mitochondria." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389869.
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Miinalainen, I. (Ilkka). "Enoyl thioester reductases—enzymes of fatty acid synthesis and degradation in mitochondria." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:9514282442.
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Abstract
Fatty acids are one of the most essential categories of biological lipids and their synthesis and degradation are vital for all organisms. Severely compromised phenotypes of yeast mutants and human patients, which have defective components in their degradative or synthetic processes for fatty acid metabolism, have highlighted the importance of these processes for overall metabolism. Most fatty acids are degraded by β-oxidation, which occurs in mitochondria and peroxisomes in mammals, whereas synthesis is catalyzed by cytosolic multifunctional peptides, although a synthesis system involving individual enzymes in mitochondria has been also proposed.
In this study a novel mitochondrial 2-enoyl thioester reductase Etr1p from the yeast Candida tropicalis, its homolog Mrf1p from Saccharomyces cerevisiae, and their mammalian ortholog were identified and characterized. Observations indicating that mitochondrial localization as well as enzymatic activity is needed to complement the respiratory-deficient phenotype of the mrf1Δ strain from S. cerevisiae suggests that Etr1p and Mrf1p might act as a part of the mitochondrial fatty acid synthesis machinery, the proper function of which is essential for respiration and the maintenance of mitochondrial morphology in yeast. The mammalian enzyme, denoted Nrbf-1p, showed similar localization, enzymatic activity, and ability to rescue the growth of the mrf1Δ strain suggesting that mammals are also likely to possess the ability and required machinery for mitochondrial fatty acid synthesis.
This study further included the characterization of another mitochondrial thioester reductase, 2,4-dienoyl-CoA reductase, which acts as an auxiliary enzyme in the β-oxidation of unsaturated fatty acids. The function of this gene was analyzed by creating a knock-out mouse model. While unstressed mice deficient in 2,4-dienoyl-CoA reductase were asymptomatic, metabolically challenged mice showed symptoms including hypoglycemia, hepatic steatosis, accumulation of acylcarnitines, and severe intolerance to acute cold exposure. Although the oxidation of saturated fatty acids proceeds normally, the phenotype was in many ways similar to mouse models of the disrupted classical β-oxidation pathway, except that an altered ketogenic response was not observed. This mouse model shows that a proper oxidative metabolism for unsaturated fatty acids is important for balanced fatty acid and energy metabolism.
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Baltazar, Maria de Fatima Monginho. "Studies of the enzymology of fatty acid oxidation and of methyl ketone production in Aspergillus niger." Thesis, University of Hull, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265127.
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Bian, Fang. "Novel Aspects of Fatty Acid Oxidation Uncovered by the Combination of Mass Isotopomer Analysis and Metabolomics." Case Western Reserve University School of Graduate Studies / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1144955161.
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Mathew, Midhu. "Cyclic fatty acid monomers of alpha-linolenic acid : isolation and separation of isomers, and effects of structural parameters on their oxidation." Master's thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/69060.
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Les monomères cycliques d'acides gras (CFAM) provenant d'huiles riches en acide alphalinolénique (18:3; ALA) sont constitués de 16 isomères de structures cycliques à 5 et 6 atomes de carbone. Ils se forment lors de traitements thermiques des huiles, comme le raffinage et la friture. Conséquemment, les CFAMs se retrouvent dans l'alimentation humaine. La littérature scientifique rapporte les résultats de travaux sur les effets métaboliques des CFAMs dont le principal est la stéatose hépatique. Les isomères cycliques à 5 et à 6 carbones se forment simultanément lors du chauffage des huiles et l'obtention de l'un ou de l'autre, bien que possible par synthèse totale et par HPLC, est laborieuse et à faibles rendements, ce qui ajoute à la difficulté de la réalisation d'études métaboliques chez l'animal avec une seule de ces deux structures. Dans la première partie des travaux, présentés au chapitre II, nous nous sommes concentrés à mieux isoler les CFAMs de l'huile de lin, suivi d'une séparation supplémentaire en leurs principaux isomères CFAM-5 et CFAM-6 de l'acide linolénique, en utilisant une combinaison de chromatographie sur couche mince argentique, pour le développement de la méthode, et de chromatographie sur colonne, pour la production de fractions. Cinq fractions ont ainsi été récupérées à partir de la chromatographie argentique sur colonne avec le système de solvants hexane-acétate d'éthyleacide acétique dans les proportions volumétriques 120:30:1 . Les isomères des CFAMs de chacune des fractions ont ensuite été identifiés par GC-MS de leurs dérivés esters picolinyles. Les résultats indiquent que la fraction F-1 contient principalement des isomères CFAM-6. Deux isomères non rapportés dans la littérature, provisoirement identifiés comme des CFAM-5 conjugués, étaient aussi présents en faible quantité dans la fraction F-1. Une autre fraction, F-3, contenait des isomères de CFAMs uniquement à cycle de 5 atomes de carbones. Cette fraction comprenait aussi une faible quantité d'isomères de l'acide alpha-linolénique. La fraction intermédiaire F-2 contenait les deux types d'isomères des CFAMs. La littérature scientifique indique que les huiles végétales alimentaires peuvent s'oxyder et qu'elles peuvent causer des effets délétères sur la santé. Cependant, aucun travaux n'a porté sur l'oxydation des CFAM, les CFAM-Ox, ni sur leurs effets métaboliques potentiels. Pourtant, des similitudes structurelles peuvent être attendues entre celles de CFAM-Ox et celles de certaines phytoprostanes (PhytoPs) et isoprostanes (IsoPs), et potentiellement des activités biologiques analogues. Ainsi, l'objectif de la seconde partie des présents travaux, présentés au chapitre III, était d'étudier l'oxydation des CFAMs de l'acide alpha-linolénique. L'oxydation de ces CFAMs di-insaturés a été réalisée sous oxygène à des températures allant de 160 à 200 °C, sur des périodes de 8 heures. Les résultats indiquent qu'environ 60% des CFAM-5 sont oxydés au bout de 2 à 4 h et que leur oxydation se produit de manière significativement plus rapide que celle des CFAM-6, et à une vitesse qui s'approche de celle de l'oxydation de l'acide linoléique, acide gras également di-insaturé. Les différences observées entre les vitesses d'oxydation des CFAM-5 et des CFAM-6 sont probablement dues à la présence de positions bis-allyliques dans les structures CFAM-5, comme il s'en trouve dans l'acide linoléique, contrairement aux CFAM-6 qui contiennent des doubles liaisons isolées, séparées par deux atomes de carbone. Ces résultats suggèrent également que les niveaux rapportés dans la littérature scientifique des CFAMs dans les huiles de friture sont nécessairement sous-estimés car ils ne tiennent pas compte des CFAM-Ox.Cyclic fatty acid monomers (CFAMs) from oils rich in alpha-linolenic acid (18: 3; ALA) consist of 16 isomers of 5 and 6 carbon ring structures. They are formed during thermal treatments of edible oils, such as refining and frying. Consequently, CFAMs are found in human food. The scientific literature reports the results of work on the metabolic effects of CFAMs, the main one of which is hepatic steatosis. The cyclic isomers of 5 and 6 carbons are formed simultaneously on heating oils and obtaining one or the other, although possible by total synthesis and HPLC, is laborious and in low yields. This contributes to the difficulty of performing metabolic studies in animals with just one of these two structures. In the first part of the work, presented in chapter II, we focused on better isolating the CFAMs from linseed oil, followed by an additional separation into their main isomers CFAM-5 and CFAM-6 of linolenic acid, using a combination of silver ion thin layer chromatography, for the development of the method, and column chromatography, for the production of fractions. Five fractions were thus recovered from silver ion column chromatography with the hexaneethyl acetate-acetic acid solvent system in volumetric proportions 120:30:1. The CFAM isomers of each of the fractions were then identified by GC-MS of their picolinic ester derivatives. The results indicate that fraction F-1 mainly contains CFAM-6 isomers. Two isomers not reported in the literature, tentatively identified as conjugated CFAM-5 isomers, were also present in small amounts in the F-1 fraction. Another fraction, F-3, contained isomers of CFAMs only with a ring of 5 carbon atoms. This fraction also contained a small amount of alpha-linolenic acid isomers. The intermediate fraction F-2 contained both types of CFAMs isomers. The scientific literature indicates that edible vegetable oils can oxidize and can cause deleterious health effects. However, no work has focused on the oxidation of CFAMs and their oxidation products, the CFAM-Ox, or their potential metabolic effects. However, structural similarities can be expected between those of CFAM-Ox and those of certain phytoprostanes (PhytoPs) and isoprostanes (IsoPs), and potentially similar biological activities. Thus, the objective of the second part of this work, presented in Chapter III, was to study the oxidation of CFAMs of alpha-linolenic acid. The oxidation of these diunsaturated CFAMs was carried out under oxygen at temperatures ranging from 160 to 200 °C, over periods of 8 hours. The results indicate that approximately 60% of CFAM-5 are oxidized after 2-4 h and that their oxidation occurs significantly faster than that of CFAM-6, and at a rate that approaches that of linoleic acid, also a di-unsaturated fatty acid. The differences observed between the oxidation rates of CFAM-5 and CFAM-6 are probably due to the presence of bis-allylic positions in CFAM-5 structures, as found in linoleic acid, unlike CFAM-6 which contain isolated double bonds separated by two carbon atoms. These results also suggest that the levels of CFAMs reported in frying oils in the scientific literature are necessarily underestimated because they do not take CFAM-Ox into account.
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Chido, Chakanya. "Fatty acid composition, colour stability and lipid oxidation of mince produced from fresh and frozen/thawed fallow deer meat." Thesis, University of Fort Hare, 2016. http://hdl.handle.net/10353/2479.
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The aim of the study was to determine the fatty acid composition, colour stability and lipid oxidation of fresh mince produced from fallow deer and to evaluate the effect of frozen storage duration on the retail display shelf life of the mince. A total of 31 fallow deer carcasses were used in the study. After cooling for 24hrs, the carcasses were deboned, external fat from the fore and hindquarter muscles removed and individually vacuum packed. For the first trial, seven fallow deer carcasses were used. Meat from the hind and fore-quarters of each carcass was divided into two equal batches per animal. One batch was minced (through a 5 mm die) and packed into oxygen permeable overwraps and refrigerated at 4°C for a period of eight days under retail display conditions. The second batch was vacuum packed and frozen at -20°C for 2 months at the end of which mince was also produced and monitored over an eight-day period under the same conditions that were used for the fresh mince. Colour, pH, lipid and myoglobin stability was determined. Proximate and fatty acid composition was also determined. No differences (P>0.05) were noted between proximate composition of fresh and frozen/thawed minced meat. The lipid content of fallow deer was 2.4 percent (±0.04). Total n3 fatty acids differed (P<0.05) between treatments and decreased with increased storage and display day. There were significant (P<0.05) treatment and time interactions on all measured colour parameters, TBARS and myoglobin forms. Fresh mince was lighter and had higher redness (a*) and yellowness (b*) values than mince from two months frozen stored meat. Hue angle for fresh mince remained stable throughout display whereas it increased for frozen/thawed mince. Fresh mince had lower TBARS values than frozen/thawed mince. Minced meat produced from frozen/thawed deer meat had higher surface met-myoglobin and total met-myoglobin percentages. Surface and total oxy-myoglobin percentage was higher in fresh mince. The first trial clearly showed colour and lipid stability differences between fresh mince and mince from frozen/thawed meat. It also showed that fresh mince has a longer retail display life than mince produced from frozen/thawed meat (six days and four days, respectively). In the second trial, the effects of frozen storage duration on colour and lipid stability were investigated. Twenty-four fallow deer were used. Twelve were harvested in June (6male 6female) and the other twelve in August (6 male 6female) of the same year.Twenty four hours after harvesting, the fore and hindquarter muscles of the carcasses were deboned, vacuum packed and kept at -20°C until October (i.e. 2months and 4months frozen storage period). Upon thawing, the meat was processed into mince following the same procedure used for the first trialand displayed for a fiveday period under retail display conditions. Frozen duration and gender had no effect (P>0.05) on the proximate composition of fallow deer meat. The total amount of saturated fatty acids (SFA) increased and total amount of poly unsaturated fatty acids (PUFA) decreased as frozen duration and display day increased (P<0.05). Frozen duration affected (P<0.01) lipid oxidation and percentage oxy-myoglobin. Mince pH and all colour parameters (L*, a*, b*,hue and chroma) differed (P<0.05) between treatments on day zero and three. Display day was a significant factor (P<0.05) on all measured parameters. By day three all parameters except pH showed signs of extended oxidation and discolouration as evidenced by reduced redness, decreased colour intensity and high TBARS values. This study showed that prolonged frozen storage negatively affects the colour and lipid stability of meat and increases oxidation of PUFAs during frozen storage. However, the study also suggests that although frozen/thawed meat has a shorter retail display shelf life; the proximate composition of the meat remains unchanged.
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Ferreira, Tânia Sofia Faria. "Utilização de semente de linho vs. banha em dietas para coelhos em crescimento suplementadas com alfarroba. Efeitos no perfil de ácidos gordos e estabilidade oxidativa da carne." Master's thesis, ISA, 2013. http://hdl.handle.net/10400.5/6121.
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Mestrado em Engenharia Zootécnica - Produção Animal - Instituto Superior de Agronomia / Faculdade de Medicina VeterináriaTo compare the effect of nature of fat and carob on rabbit´s productive parameters, digestive performance, fatty acid profile and meat susceptibility to oxidation, four experimental diets was formulated – linseed without carob (LL), linseed with carob (LA), lard without carob (BB) and lard with carob (BA). Diets were distributed to 48 rabbits (12 per diet), housed individually, from 28 to 70 days old. The source of fat had no effect on the animals live weight, while the presence of carob affected (P=0,002) the conversion ratio (2,72 and 2,89 for diets without and with carob, respectively). The apparent digestibility of crude fat was higher (P<0,0001) in linseed diets (90,2 and 84,4% for linseed and lard diets, respectively). The inclusion of carob negatively affected (P<0,0001, in both cases) the organic matter digestibility (64,3 and 61,1% for diets without and with carob, respectively) and crude protein (78,7 and 69,8% for diets without and with carob, respectively). The fatty acid composition of meat was affected by the source of fat – lard diets increased the saturated fatty acids concentration (23 vs. 32,7% of total fatty acids), while linseed diets increased polyunsaturated fatty acids, including n-3 family (22,4 vs. 52,6% for PUFA and 2,3 vs. 33,3% for n-3 PUFA). Induced oxidation susceptibility was higher in LL diets (37,3; 29,3; 13,8 and 23,4 mg MDA kg-1 of meat to LL, LA, BB and BA diets, respectively). There was no antioxidant activity of carob.
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Gonçalves, Joana Fernandes. "Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate." Master's thesis, Faculdade de Ciências e Tecnologia, 2012. http://hdl.handle.net/10362/8198.
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Dissertação para obtenção do Grau de Mestre em
BiotecnologiaFsp27 (CIDEC the human homologue) is a lipid droplet protein that when overexpressed down regulates fatty acid oxidation (FAO). Previous results of this group showed that Fsp27/CIDEC expression is regulated by fasting in liver in a time-dependent manner. The present study aimed to elucidate the mechanism by which Fsp27/CIDEC is mediating fasting adaptation and regulated by FAO rate in liver. We showed that induction of Fsp27/CIDEC expression during fasting is not regulated by PPARα. Pharmacological inhibition of FAO by etomoxir induces Fsp27/CIDEC in fasting conditions and this regulation is not mediated by PPAR – a master regulator in triglyceride accumulation. The early response to fasting can be explained by a canonical PKA-CREB-CRTC2 signaling pathway, since CIDEC expression was increased by forskolin which effect was lost when a vector containing a dominant negative of CREB construct(KCREB) was co-transfected in HepG2 cells, and, consistently, Fsp27 promoter activity was increased by CREB. Also, CIDEC expression was up-regulated by specific Sirt1 depletion by siRNA in HepG2 cells. Our data demonstrate that Fsp27/CIDEC is a CREB target gene that could be up-regulated when FAO is reduced and that fluctuations in SIRT1 activity, in response to nutrient availability, mediate this mechanism. The peroxissome proliferator-activated receptor gamma coactivator-1α (PGC-1α) induces and coordinates gene expression that stimulates metabolic pathways linked to the fasted response in liver including gluconeogenesis. We observed that Pgc-1α expression was increased in late fasting in the liver of mice previously subjected to a leucin deprived diet. These conditions also enhanced transcription from Foxa2 gene. This study showed that the mechanism regulating the induction of Pgc-1α expression under these conditions is not mediated by the recruitment of CREB by Foxa2 to the Pgc-1α or the Pepck promoters, since both promoters activities were not enhanced by the co-transfection of FOXA2 with CREB in HepG2 cells.
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Westman, Ola. "Effects of perfluorinated compounds on hepatic fatty acid oxidation in avian embryos using a tritium release assay." Thesis, Örebro universitet, Akademin för naturvetenskap och teknik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-14332.
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The large use of perfluorinated compounds (PFCs) to produce fluoropolymers in consumer and industrial applications, including insecticides, plastics, non-stick surfaces and fire fighting foams has led to a well known widespread occurrence and high concentrations are found in wild life including avian species. For instance, concentrations of perfluorooctane sulfonate (PFOS) in eggs from the common guillemot in the Baltic Sea are among the highest in the Nordic environment. In our laboratory studies, PFOS has caused early mortality in chicken at doses close to concentrations found in eggs of the Baltic guillemot. The mechanisms behind the avian toxicity are unclear but many studies suggest mechanisms including lipid homeostasis. We have designed a method in which hepatic embryonic tissue from chicken (Gallus domesticus) is used to investigate the effects of PFCs on the β-oxidation of fatty acids. The purpose of this project was to assess the effects of PFOS, perfluorooctanoic acid (PFOA) or perfluorobutane sulfonate (PFBS) on the hepatic fatty acid oxidation using an egg injection technique followed by the use of a tritium release assay with palmitate (16:0) as substrate. The embryos were exposed in ovo and on day 10 of incubation embryo livers are incubated in vitro with tritiated fatty acids. The β-oxidation was significantly induced after exposed to 1 mg/kg PFOS (p = 0.003) and 10 mg/kg PFOS (p = 0.04), and difference in oxidation values was 39% and 34% respectively compared to control. The oxidation effect was not significant (p > 0.05) in samples exposed to PFOA (4 mg/kg) or PFBS (20 mg/kg), however noted, the difference in oxidation values was 18% and 30.5% respectively, compared to control calculated on current average. The results show that in ovo exposure in combination with an in vitro method, using a tritium release assay to detect effects on the β-oxidation of fatty acids in avian embryo hepatic tissue could be a useful method to elucidate possible mechanisms behind avian developmental toxicity.
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Zhang, Shuai. "Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/24536.
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The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The Virginia lines of chickens are a unique model of anorexia and obesity that have resulted from 56 generations of artificial selection for high (HWS) or low (LWS) juvenile body weight. We hypothesized that hyperphagia and obesity in juvenile HWS chickens are associated with altered fatty acid oxidation efficiency and metabolic flexibility in tissues associated with energy sensing and storage, and relative cellular hypertrophy in white adipose tissue. Hypothalamus, liver, Pectoralis major, gastrocnemius, abdominal fat, clavicular fat and subcutaneous fat were collected from juvenile (56-65 day-old) HWS and LWS chickens for metabolic, gene expression and histological assays. The HWS chickens had reduced fatty acid oxidation efficiency in abdominal fat (P < 0.0001) and reduced rates of oxidation in abdominal fat and gastrocnemius (P < 0.0001) as compared to LWS. There was reduced citrate synthase activity in white adipose tissue (P < 0.0001) and greater metabolic inflexibility in skeletal muscle (P = 0.006) of HWS compared to LWS. Greater pyruvate dehydrogenase kinase 4 (PDK4) and forkhead box O1 (FoxO1) mRNA were found in skeletal muscle and white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in all adipose tissue depots was greater (P < 0.05) in LWS than in HWS chickens. The HWS chickens had larger (P < 0.0001) and fewer (P < 0.0001) adipocytes per unit area than LWS. These results suggest that the HWS chickens have impaired metabolic flexibility and fatty acid oxidation efficiency due to an up-regulation of pyruvate dehydrogenase activity to accommodate the influx of acetyl CoA from fatty acid oxidation in skeletal muscle and white adipose tissue. These metabolic adaptations can be linked to differences in gene expression regulation and body composition between the lines. Adipocyte cellularity data are consistent with greater oxidative efficiency in the adipose tissue of LWS, because of the greater number of unfilled cells in all depots that were sampled. Results can be extrapolated to agricultural production in the understanding of factors regulating the amount of lipid deposition in chicken carcass fat. Results may also provide insight into eating disorders and the development of obesity.Master of Science
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Kruger, F. C. "A study of non-alcoholic fatty liver disease (NAFLD) in South African patients and analysis of candidate genes in insulin resistance and fatty acid oxidation." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/1415.
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Thesis (PhD (Medicine. Internal Medicine))--Stellenbosch University, 2008.Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in Western countries, extending from steatosis (FLD) to steatohepatitis (NASH). Differentiation between NASH and nonprogressive NAFLD is difficult on clinical grounds therefore a need exists to identify reliable biomarkers of disease progression. The aims of the study were 1) to describe the disease profile of NAFLD/NASH in South African patients of the Western Cape, 2) to investigate the metabolic derangements associated with this condition, including insulin resistance, lipid abnormalities and liver fibrogenesis, and 3) to assess the possible involvement of candidate genes in relation to the disease phenotype in the patient cohort. A total of 233 patients (73% female) were enrolled in this study, consisting of 69% Cape Coloured, 25% Caucasian, 5% Black and 1% Asian individuals. All subjects were obese or overweight based on the assessment of body mass index (BMI). Screening for NAFLD identified 182 patients (87%) with ultrasonographical evidence of fatty infiltration and/or hepatomegaly. Liver biopsies were performed on patients with persistently abnormal liver functions and/or hepatomegaly. NAFLD was confirmed histologically in 111 patients of whom 36% had NASH and 17% advanced liver fibrosis. None of the Black patients had advanced fibrosis.
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Kuršvietienė, Lolita. "Riebalų rūgščių vaidmuo reguliuojant mitochondrijų kvėpavimą." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2007. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2007~D_20070531.081711-68424.
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Šiame darbe siekta išsiaiškinti riebalų rūgščių vaidmenį reguliuojant oksidacinį fosforilinimą saponinu permeabilizuotose žiurkės širdies raumens skaidulose. Pagrindiniai darbo uždaviniai: 1).Įvertinti įvairios struktūros riebalų rūgščių vaidmenį reguliuojant oksidacinį fosforilinimą saponinu permeabilizuotose žiurkės širdies raumens skaidulose;2) Naudojant egzogeninę ADP-suvartojančią piruvato kinazės ir fosfoenolpiruvato sistemą įvertinti, ar oksiduojantis riebalų rūgštims kinta išorinės mitochondrijų membranos laidumas ADP-ui; 3) Tirti, ar riebalų rūgščių oksidacija veikia funkcinę sąveiką tarp kreatino kinazės ir ADP/ATP nešiklio; 4).Nustatyti riebalų rūgščių oksidacijos poveikį mitochondrijų in situ morfologijai bei įvertinti dekstrano T70 poveikį mitochondrijų in situ kvėpavimo parametrams ir morfologijai.
Mitochondrijose in situ oksiduojantis įvairios struktūros riebalų rūgštims, vienoms ar mišinyje su piruvatu+malatu, oksidacinio fosforilinimo tariamoji KmADP sumažėja panašiu laipsniu lyginant su piruvato+malato oksidacija. Šis poveikis yra grįžtamas, t.y. riebalų rūgščių oksidacija nedaro įtakos po jos vykstančiai neriebalinės kilmės substratų oksidacijai. Oksiduojantis riebalų rūgštims išsaugoma funkcinė sąveika tarp kreatino kinazės ir ANT, nepaisant ženklaus tar. KmADP reikšmės sumažėjimo. Elektroninės mikroskopijos metodu įvertinome, kad riebalų rūgščių sąlygotas KmADP sumažėjimas gali būti susijęs su mitochondrijų struktūros pokyčiais, kuriuos sukelia riebalų... [to full text]The aim of this study was to investigate the influence of fatty acid oxidation on the regulation of oxidative phosphorylation in permeabilized rat cardiac fibers. The objectives of the study:1). To evaluate the influence of different fatty acids in the regulation of oxidative phosphorylation in fibers; 2). To evaluate the changes in outer mitochondrial membrane permeability for ADP during fatty acid oxidation by the means of exogenous ADP consuming system consisting of pyruvate kinase and phosphoenolpyruvate;3); To investigate the effect of fatty acid oxidation on the functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase; 4). To investigate the effects of fatty acid oxidation and dextran T70 on the morphology and respiration of mitochondria in saponin-permeabilized rat cardiac fibers. The apparent Km of oxidative phosphorylation for ADP in saponin-permeabilized rat cardiac fibers is decreased several fold during oxidation of fatty acids alone or in the mixture with pyruvate compared to oxidation of pyruvate+malate. This effect is reversible, and fatty acid oxidation does not influence the subsequent oxidation of non-fatty substrates. The functional coupling between creatine kinase and adenine nucleotide translocase is not influenced by fatty acid oxidation and the efficiency of creatine kinase system does not depend on the nature of respiratory substrates. Analysis of electron microscopy images of fibres indicates that morphological... [to full text]
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Wang, Xiao. "Investigation of Anaplerosis from Propionyl-CoA Precursors and Fatty Acid Oxidation in the Brain of VLCAD and Control Mice." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1232676063.
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Montgomery, Jane Aimée. "A mass spectrometric investigation of two rat models of defective medium chain fatty acid oxidation using deuterium labelled substrates /." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75845.
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Medium chain fatty acid oxidation was investigated in riboflavin deficient and 2-octynoic acid treated rats. Urinary metabolites of deuterium labelled fatty acid substrates were determined using gas chromatography-mass spectrometry. Control and experimental animals both produced labelled dicarboxylic acids. The ratio of chain length of dicarboxylates (C$ sb{ rm n+2}$/C$ sb{ rm c}$) was lowest in riboflavin deficient rats. As mitochondrial $ beta$-oxidation is inhibited, Peroxisomal $ beta$-oxidation appears to increase in response to inhibited mitochondrial oxidation in riboflavin deficiency. Administration of L-carnitine with the labelled substrates to half the rats showed that there were no differences in organic acid excretion between carnitine supplemented and unsupplemented rats. A new method to quantitate individual acylcarnitines in urine using fast atom bombardment-mass spectrometry and deuterium labelled acylcarnitines as internal standards demonstrated that administration of L-carnitine did enhance excretion of free carnitine and short chain acylcarnitines along with some dicarboxylcarnitines in all groups.
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Sparks, Darrell Lynn. "Oxidation of lipids in a supercritical-fluid medium." Diss., Mississippi State : Mississippi State University, 2008. http://library.msstate.edu/etd/show.asp?etd=etd-03252008-162949.
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Ma, Tiezheng. "Oxidation Kinetics of Methyl Linoleate and α-Linolenate in Bulk and Oil-in-water Emulsion Systems." Kyoto University, 2014. http://hdl.handle.net/2433/188751.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第18313号
農博第2038号
新制||農||1020(附属図書館)
学位論文||H26||N4820(農学部図書室)
31171
京都大学大学院農学研究科食品生物科学専攻
(主査)教授 安達 修二, 教授 河田 照雄, 教授 保川 清
学位規則第4条第1項該当
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Sharma, Arpit. "The role of the skeletal muscle mitochondrial pyruvate carrier in systemic glucose homeostasis and whole-body adiposity." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6640.
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Metabolic cycles are a fundamental element of cellular and organismal function. Among the most critical in higher organisms is the Cori Cycle, the systemic cycling between lactate and glucose. Here, skeletal muscle-specific Mitochondrial Pyruvate Carrier (MPC) deletion in mice increased muscle glucose uptake but diverted pyruvate into the circulation as lactate, driving increased Cori Cycling and energy expenditure. Loss of muscle MPC activity evoked adaptive glutaminolysis, increased fatty acid oxidation, and resulted in a striking resistance to gains in fat mass with age with perfect sparing of muscle mass and strength. Furthermore, chronic and acute muscle MPC deletion accelerated fat mass loss on a normal diet after high fat diet-induced obesity. Our results illuminate the role of the skeletal muscle MPC as a central node for whole-body carbohydrate, fat, and amino acid metabolism. They highlight the potential utility of decreasing muscle pyruvate oxidation to ameliorate obesity and type 2 diabetes.