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Lipid Biosynthesis (lipid + biosynthesis)
Selected AbstractsTheoretical study of lipid biosynthesis in wild-type Escherichia coli and in a protoplast-type L-form using elementary flux mode analysisFEBS JOURNAL, Issue 4 2010Dimitar Kenanov In the present study, we investigated lipid biosynthesis in the bacterium Escherichia coli by mathematical modeling. In particular, we studied the interaction between the subsystems producing unsaturated and saturated fatty acids, phospholipids, lipid A, and cardiolipin. The present analysis was carried out both for the wild-type and for several in silico knockout mutants, using the concept of elementary flux modes. Our results confirm that, in the wild type, there are four main products: L1-phosphatidylethanolamine, lipid A, lipid A (cold-adapted), and cardiolipin. We found that each of these compounds is produced on several different routes, indicating a high redundancy of the system under study. By analysis of the elementary flux modes remaining after the knockout of genes of lipid biosynthesis, and comparison with publicly available data on single-gene knockouts in vivo, we were able to determine the metabolites essential for the survival of the cell. Furthermore, we analyzed a set of mutations that occur in a cell wall-free mutant of Escherichia coli W1655F+. We postulate that the mutant is not capable of producing both forms of lipid A, when the combination of mutations is considered to make a nonfunctional pathway. This is in contrast to gene essentiality data showing that lipid A synthesis is indispensable for the survival of the cell. The loss of the outer membrane in the cell wall-free mutant, however, shows that lipid A is dispensable as the main component of the outer surface structure in this particular E. coli strain. [source] Optimization of the culturing conditions of human umbilical cord blood-derived endothelial colony-forming cells under xeno-free conditions applying a transcriptomic approachGENES TO CELLS, Issue 7 2010Steffen M. Zeisberger Establishment of fetal bovine serum (FBS)-free cell culture conditions is essential for transplantation therapies. Blood-derived endothelial colony-forming cells (ECFCs) are potential candidates for regenerative medicine applications. ECFCs were isolated from term umbilical cord blood units and characterized by flow cytometry, capillary formation and responsiveness to cytokines. ECFCs were expanded under standard, FBS-containing endothelial medium, or transferred to chemically defined endothelial media without FBS. Microarray expression profiling was applied to compare the transcriptome profiles in FBS-containing versus FBS-free culture. ECFC outgrowth in standard medium was successful in 92% of cord blood units. The karyotype of expanded ECFCs remained normal. Without FBS, ECFC initiation and expansion failed. Modest proliferation, changes in cell morphology and organization and cell death have been observed after passaging. Gene ontology analysis revealed a broad down-regulation of genes involved in cell cycle progression and up-regulation of genes involved in stress response and apoptosis. Interestingly, genes participating in lipid biosynthesis were markedly up-regulated. Detection of several endothelial cell-specific marker genes showed the maintenance of the endothelial cell characteristics during serum-free culture. Although ECFCs maintain their endothelial characteristics during serum-free culturing, they could not be expanded. Additional supply of FBS-free media with lipid concentrates might increase the ECFC survival. [source] FoxO1 , the key for the pathogenesis and therapy of acne?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 2 2010Bodo C. Melnik Summary Five main factors play a pivotal role in the pathogenesis of acne: androgen dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis, increased colonization with P. acnes, and inflammatory events. This paper offers a solution for the pathogenesis of acne and explains all major pathogenic factors at the genomic level by a relative deficiency of the nuclear transcription factor FoxO1. Nuclear FoxO1 suppresses androgen receptor, other important nuclear receptors and key genes of cell proliferation, lipid biosynthesis and inflammatory cytokines. Elevated growth factors during puberty and persistent growth factor signals due to Western life style stimulate the export of FoxO1 out of the nucleus into the cytoplasm via activation of the phos-phoinositide-3-kinase (PI3K)/Akt pathway. By this mechanism, genes and nuclear receptors involved in acne are derepressed leading to increased androgen receptor-mediated signal transduction, increased cell proliferation of androgen-dependent cells, induction of sebaceous lipogenesis and upregulation of Toll-like-receptor-2-dependent inflammatory cytokines. All known acne-inducing factors exert their action by reduction of nuclear FoxO1 levels. In contrast, retinoids, antibiotics and dietary intervention will increase the nuclear content of FoxO1, thereby normalizing increased transcription of genes involved in acne. Various receptor-mediated growth factor signals are integrated at the level of PI3K/Akt activation which finally results in nuclear FoxO1 deficiency. [source] Modulation of white adipose tissue proteome by aging and calorie restrictionAGING CELL, Issue 5 2010Adamo Valle Summary Aging is associated with an accrual of body fat, progressive development of insulin resistance and other obesity comorbidities that contribute to decrease life span. Caloric restriction (CR), which primarily affects energy stores in adipose tissue, is known to extend life span and retard the aging process in animal models. In this study, a proteomic approach combining 2-DE and MS was used to identify proteins modulated by aging and CR in rat white adipose tissue proteome. Proteomic analysis revealed 133 differentially expressed spots, 57 of which were unambiguously identified by MS. Although CR opposed part of the age-associated protein expression patterns, many effects of CR were on proteins unaltered by age, suggesting that the effects of CR on adipose tissue are only weakly related to those of aging. Particularly, CR and aging altered glucose, intermediate and lipid metabolism, with CR enhancing the expression of enzymes involved in oxalacetate and NADPH production, lipid biosynthesis and lipolysis. Consistently, insulin-, and ,3-adrenergic receptors were also increased by CR, which denotes improved sensitivity to lipogenic/lipolytic stimuli. Other beneficial outcomes of CR were an improvement in oxidative stress, preventing the age-associated decrease in several antioxidant enzymes. Proteins involved in cytoskeleton, iron storage, energy metabolism and several proteins with novel or unknown functions in adipose tissue were also modulated by age and/or CR. Such orchestrated changes in expression of multiple proteins provide insights into the mechanism underlying CR effects, ultimately allowing the discovery of new markers of aging and targets for the development of CR-mimetics. [source] Control of fatty acid desaturation: a mechanism conserved from bacteria to humansMOLECULAR MICROBIOLOGY, Issue 6 2006Pablo S. Aguilar Summary Unsaturated fatty acids (UFAs) have profound effects on the fluidity and function of biological membranes. Microorganisms, plants and animals regulate the synthesis of UFAs during changing environmental conditions as well as in response to nutrients. UFAs homeostasis in many organisms is achieved by feedback regulation of fatty acid desaturase gene transcription through signalling pathways that are governed by sensors embedded in cellular membranes. Here, we review recently discovered components of the regulatory machinery governing the transcription of fatty acid desaturases in bacteria, yeasts and animals that indicate an ancient role of transmembrane signalling mechanisms and integrate membrane composition with lipid biosynthesis. [source] From pre-cells to Eukarya , a tale of two lipidsMOLECULAR MICROBIOLOGY, Issue 1 2003G. Wächtershäuser Summary A mechanistic hypothesis for the origin of the three domains of life is proposed. A population of evolving pre-cells is suggested to have had a membrane of a racemate of chiral lipids that continuously underwent spontaneous symmetry breaking by spatial phase segregation into two enantiomerically enriched membrane domains. By frequent pre-cell fusions and fissions these membrane domains became partitioned between two pre-cell subpopulations having predominantly one lipid enantiomer or the other. The origin of the Bacteria and Archaea is explained by divergence of first a population of proto-bacteria and later a population of proto-archaea from the evolving pre-cells, each by the emergence of an enantio-selective lipid biosynthesis within the corresponding pre-cell subtype. The origin of the Eukarya is explained by symbiosis between a population of Bacteria and a subpopulation of pre-cells with a predominance of the bacteria-type lipid enantiomers. [source] Differential proteomic analysis of the endoplasmic reticulum from developing and germinating seeds of castor (Ricinus communis) identifies seed protein precursors as significant components of the endoplasmic reticulumPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 9 2007Daniel J. Maltman Abstract The endoplasmic reticulum is a major compartment of storage protein and lipid biosynthesis. Maximal synthesis of these storage compounds occurs during seed development with breakdown occurring during germination. In this study, we have isolated four independent preparations of ER from both developing and germinating seeds of castor bean (Ricinus communis) and used 2-D DIGE, and a combination of PMF and MS/MS sequencing, to quantify and identify differences in protein complement at both stages. Ninety protein spots in the developing seeds are up-regulated and 19 individual proteins were identified, the majority of these are intermediates of seed storage synthesis and protein folding. The detection of these transitory storage proteins in the ER is discussed in terms of protein trafficking and processing. In germinating seed ER 15 spots are elevated, 5 of which were identified, amongst them was malate synthetase which is a component of the glyoxysome which is believed to originate from the ER. Notably no proteins involved in complex lipid biosynthesis were identified in the urea soluble ER fraction indicating that they are probably all integral membrane proteins. [source] The soybean Dof-type transcription factor genes, GmDof4 and GmDof11, enhance lipid content in the seeds of transgenic Arabidopsis plantsTHE PLANT JOURNAL, Issue 4 2007Hui-Wen Wang Summary Soybean is one of the most important leguminous seed crops among the oil crops. Although the pathways for lipid biosynthesis have been identified, the factors that regulate the biosynthetic pathways at the transcriptional level are largely unknown. Here, we report our findings on the involvement of soybean Dof-type transcription factor genes in the regulation of the lipid content in soybean seeds. We identified 28 Dof-type transcription factor genes in soybean plants, and these genes displayed diverse patterns of expression in various organs. Seven flower/pod-specific genes and one constitutively expressed gene were further investigated. The proteins encoded by these seven genes were localized in the nucleus, and exhibited different abilities for transcriptional activation and DNA binding. Two genes, GmDof4 and GmDof11, were found to increase the content of total fatty acids and lipids in GmDof4 and GmDof11 transgenic Arabidopsis seeds. We also found that the 1000-seed weight was increased in the GmDof4 and GmDof11 transgenic plants. Using microarray and DNA binding analysis, we found that the two Dof-like proteins, GmDof4 and GmDof11, activated the acetyl CoA carboxylase gene and long-chain-acyl CoA synthetase gene, respectively, by direct binding to the cis -DNA elements in their promoter regions. In addition, both proteins downregulated the storage protein gene, CRA1, through direct binding. These results suggest that the two GmDof genes may augment the lipid content of soybean seeds by upregulating genes that are associated with the biosynthesis of fatty acids. [source] Association of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in KoreansANNALS OF HUMAN GENETICS, Issue 1 2009H.-J. Lee Summary Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 , 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population. [source] | |||||||||||||