A total synthesis of dl-cerulenin: a novel fatty acid antibiotic and lipid synthesis inhibitor

1977 ◽  
Vol 99 (8) ◽  
pp. 2805-2806 ◽  
Author(s):  
Robert K. Boeckman ◽  
Edward W. Thomas
Keyword(s):  
Fatty Acid ◽  
Total Synthesis ◽  
Lipid Synthesis ◽  
Synthesis Inhibitor

scholarly journals First total synthesis of the (±)-2-methoxy-6-heptadecynoic acid and related 2-methoxylated analogs as effective inhibitors of the Leishmania topoisomerase IB enzyme

2012 ◽  
Vol 84 (9) ◽  
pp. 1867-1875 ◽  
Author(s):  
Néstor M. Carballeira ◽  
Michelle Cartagena ◽  
Fengyu Li ◽  
Zhongfang Chen ◽  
Christopher F. Prada ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Total Synthesis ◽  
Leishmania Donovani ◽  
Dna Topoisomerase ◽  
Triple Bonds ◽  
Weak Intermolecular Interactions ◽  
Topoisomerase Ib ◽  
Effective Inhibition ◽  
Acetylenic Fatty Acid

The fatty acids (±)-2-methoxy-6Z-heptadecenoic acid, (±)-2-methoxy-6-hepta-decynoic acid, and (±)-2-methoxyheptadecanoic acid were synthesized and their inhibitory activity against the Leishmania DNA topoisomerase IB enzyme (LdTopIB) determined. Both 2-OMe-17:1 fatty acids were synthesized from 4-bromo-1-pentanol, the olefinic fatty acid in 10 steps and in 7 % overall yield, while the acetylenic fatty acid in 7 steps and in 14 % overall yield. The 2-OMe-17:0 acid was prepared in 6 steps and in 42 % yield from 1-hexa-decanol. The 2-OMe-17:1 acids inhibited LdTopIB, with the acetylenic acid displaying an EC50 = 16.6 ± 1.1 μM, but the 2-OMe-17:0 acid did not inhibit LdTopIB. The (±)-2-methoxy-6Z-heptadecenoic acid preferentially inhibited LdTopIB over the human TopIB enzyme. Unsaturation seems to be a prerequisite for effective inhibition, rationalized in terms of weak intermolecular interactions between the active site of LdTopIB and either the double or triple bonds of the fatty acids. Toxicity toward Leishmania donovani promastigotes was also investigated, resulting in the order acetylenic > olefinic > saturated with the (±)-2-methoxy-6-heptadecynoic acid displaying an EC50 = 74.0 ± 17.1 μM. Our results indicate that α-methoxylation decreases the toxicity of C17:1 fatty acids toward L. donovani promastigotes, but improves their selectivity index.

scholarly journals Modulation of lipid-synthesizing enzymes by insulin in differentiated ob17 adipose-like cells

1983 ◽  
Vol 214 (2) ◽  
pp. 443-449 ◽  
Author(s):  
P Grimaldi ◽  
C Forest ◽  
P Poli ◽  
R Negrel ◽  
G Ailhaud
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Specific Activity ◽  
Fatty Acid Synthetase ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Acetate Incorporation ◽  
Long Term Effects ◽  
Response Curves ◽  
Glycerol 3 Phosphate Dehydrogenase

ob17 cells convert into adipose-like cells when maintained in the presence of physiological concentrations of insulin and tri-iodothyronine. After this conversion, insulin removal from differentiated ob17 cells gives within 24-48 h a large decrease in fatty acid synthetase, glycerol 3-phosphate dehydrogenase and acid:CoA ligase activities, as well as in the rate of fatty acid synthesis determined by [14C]acetate incorporation into lipids. All parameters are restored by insulin addition to initial values within 24-48 h. Dose-response curves of insulin on the restoration of glycerol 3-phosphate dehydrogenase activity and of fatty acid synthesis give half-maximally effective concentrations close to 1 nM, in agreement with the affinity for insulin of the insulin receptors previously characterized in these cells. Immunotitration experiments indicate that the changes in the specific activity of fatty acid synthetase are due to parallel changes in the cellular enzyme content. Therefore the ob17 cell line should be a useful model to study the long-term effects of insulin on the modulation of lipid synthesis in adipose cells.

Aspects of lipid synthesis, hydrolysis, and transport studied in selected Amazon fish

1978 ◽  
Vol 56 (4) ◽  
pp. 787-792 ◽  
Author(s):  
John S. Patton ◽  
Monty S. Haswell ◽  
Thomas W. Moon
Keyword(s):  
Fatty Acid ◽  
Lipolytic Activity ◽  
Lipid Synthesis ◽  
Blood Lipid ◽  
Dietary Lipid ◽  
Indwelling Catheter ◽  
Ph Optimum ◽  
Mesenteric Fat ◽  
Fatty Acid Release ◽  
Amazon Fish

Comparative lipogenic activities offish tissue, lipolytic activity of mesenteric fat and mode of intestinal lipid release into blood were investigated in a variety of Amazon fish. Small catfish were injected intramuscularly with [1-l4C]acetate, killed at intervals, and the lipid radioactivity of 11 separate tissues determined. In 6- and 18-h fish, the heart, eyes, dark muscle, and white muscle synthesized negligible lipid relative to the other tissues. Acetone powders of Triportheus sp, mesenteric fat contained high amounts of triglyceride lipase activity (120 nmol fatty acid release-d/min per milligram protein). The activity exhibited a pH optimum of 8.0 and was not activated by albumin, bile salts, or divalent salts nor inhibited by 1 M NaCl. Characteristics of the observed activity are identical with those of mammalian pancreatic lipase. Hoplias malabaricus were fed [1-14C]oleic acid and a chronic indwelling catheter was placed in the dorsal aorta for blood sampling. Based on the distribution of radioactivity among blood lipid classes, it is suggested that dietary lipid enters fish circulatory systems both as free fatty acid and as lipoproteins.

scholarly journals Asymmetric and Regiospecific Synthesis of Isotopically Labelled Cyclopropane Fatty Acid (9R,10S)-Dihydrosterculic Acid: Overcoming Spontaneous Protonation During Lithium-Sulfoxide Exchange­

SynOpen ◽  
2018 ◽  
Vol 02 (02) ◽  
pp. 0168-0175
Author(s):  
Samuel Shields ◽  
Peter Buist ◽  
Jeffrey Manthorpe
Keyword(s):  
Fatty Acid ◽  
Total Synthesis ◽  
Cyclopropane Ring ◽  
Rapid Quenching ◽  
Cyclopropane Fatty Acid ◽  
Deuterium Incorporation ◽  
Biologically Relevant ◽  
Dihydrosterculic Acid

The total synthesis of isotopically labelled (9R,10S)-dihydro­sterculic acid, a usual cyclopropane fatty acid with biologically relevant toxicity upon desaturation in vivo, is reported. A diastereoselective Corey­–Chaykovsky reaction was employed to form the cyclopropane ring. Rapid quenching of a lithium-sulfoxide exchange was required to achieve the requisite high levels of deuterium incorporation.

scholarly journals Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages

2018 ◽  
Vol 59 (6) ◽  
pp. 994-1004 ◽  
Author(s):  
David Dubois ◽  
Stella Fernandes ◽  
Souad Amiar ◽  
Sheena Dass ◽  
Nicholas J. Katris ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Toxoplasma Gondii ◽  
Isotope Labeling ◽  
De Novo ◽  
Lipid Synthesis ◽  
Minor Effect ◽  
Parasite Line ◽  
Acetyl Coa ◽  
Apicomplexan Parasites ◽  
A Minor

Apicomplexan parasites are pathogens responsible for major human diseases such as toxoplasmosis caused by Toxoplasma gondii and malaria caused by Plasmodium spp. Throughout their intracellular division cycle, the parasites require vast and specific amounts of lipids to divide and survive. This demand for lipids relies on a fine balance between de novo synthesized lipids and scavenged lipids from the host. Acetyl-CoA is a major and central precursor for many metabolic pathways, especially for lipid biosynthesis. T. gondii possesses a single cytosolic acetyl-CoA synthetase (TgACS). Its role in the parasite lipid synthesis is unclear. Here, we generated an inducible TgACS KO parasite line and confirmed the cytosolic localization of the protein. We conducted 13C-stable isotope labeling combined with mass spectrometry-based lipidomic analyses to unravel its putative role in the parasite lipid synthesis pathway. We show that its disruption has a minor effect on the global FA composition due to the metabolic changes induced to compensate for its loss. However, we could demonstrate that TgACS is involved in providing acetyl-CoA for the essential fatty elongation pathway to generate FAs used for membrane biogenesis. This work provides novel metabolic insight to decipher the complex lipid synthesis in T. gondii.

scholarly journals Integrated Analysis of Seed microRNA and mRNA Transcriptome Reveals Important Functional Genes and microRNA-Targets in the Process of Walnut (Juglans regia) Seed Oil Accumulation

2020 ◽  
Vol 21 (23) ◽  
pp. 9093
Author(s):  
Xinchi Zhao ◽  
Guiyan Yang ◽  
Xiaoqiang Liu ◽  
Zhongdong Yu ◽  
Shaobing Peng
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Juglans Regia ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Integrated Analysis ◽  
Regulation Mechanism ◽  
Oil Accumulation ◽  
Walnut Oil ◽  
Regulatory Modules

Walnut (Juglans regia) is known as a promising woody oil crop with abundant polyunsaturated fatty acids in its kernel. However, the regulation mechanism of walnut oil accumulation and fatty acid metabolism is still poorly understood, which restricted the breeding and genetic improvement of high-quality oil-bearing walnuts. To reveal the molecular mechanism of walnut oil accumulation, considering the potential regulation of microRNA (miRNA) in seed development, in this study, the oil content of walnut kernel on the 80th, 100th and 120th day after flowering (DAF) was tested and the corresponding proportions are 11.51%, 40.40% and 53.20%. Between DAF of 80th~120th, the content of stearic acid and oleic acid tended to increase, but the proportion of other fatty acids tended to decrease. Meanwhile, comparative transcriptome and sRNA-seq analysis on three stages (80th, 100th and 120th DAF), found 204 conserved miRNAs and 554 novel miRNAs in walnut kernels, among which 104 key genes related to walnut oil accumulation were screened. The phospholipid:diacylglycerol acyltransferase metabolic pathway may contribute more to oil accumulation in walnut. 16 miRNA-mRNA regulatory modules related to walnut oil accumulation and fatty acid synthesis were constructed. 8 known miRNAs and 9 novel miRNAs regulate 28 genes involved in fatty acid (FA) metabolism and lipid synthesis. Among them, jre-miRn105, jre-miRn434, jre-miR477d and jre-miR156a.2 are key miRNAs that regulate walnut FA synthesis. Jre-miRn411 and jre-miR399a.1 are closely related to oil accumulation. These data provide new insights and lay the foundation for subsequent studies on walnut FA synthesis and oil accumulation.

Effect of aging on lipid composition and metabolism in the adipose tissues of the rat

1961 ◽  
Vol 201 (3) ◽  
pp. 540-546 ◽  
Author(s):  
William Benjamin ◽  
Alfred Gellhorn ◽  
Mary Wagner ◽  
Harold Kundel
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Palmitic Acid ◽  
Subcutaneous Fat ◽  
Lipid Synthesis ◽  
Pentose Phosphate ◽  
Acid Oxidation ◽  
Acetate Incorporation ◽  
Adipose Tissues

Lipid metabolism and chemistry was studied in adipose tissues of the rat from the age of 38 days to 647 days. Aging process was characterized by a marked decrease in lipid synthesis from acetate, a reduction in the proportion of glucose metabolized by the pentose phosphate pathway, and a lower rate of palmitate incorporation into the mixed lipids. Oxidation of palmitic acid to CO2 and release of free fatty acid by epididymal fat was the same in young and old tissues under control conditions; when, however, glucose was absent from the medium or when epinephrine was added, there was a significantly greater rate of palmitic acid oxidation and free fatty acid release by young compared to old adipose tissue. Rate of acetate incorporation into mixed lipids by multiple adipose tissue sites was determined at different ages. Consistently greater rates of lipid biosynthesis were found in the epididymal, perirenal, mesenteric and interscapular adipose tissues than in subcutaneous fat at all ages. Rate of lipid synthesis by the interscapular fat (unlike any of the other depots) remained high at all ages studied. A greater proportion of short chain fatty acids was found in adipose tissues from young rats than in the old. This was related to fatty acid composition of rat milk.

Baicalin Inhibits Coxsackievirus B3 Replication by Reducing Cellular Lipid Synthesis

2020 ◽  
Vol 48 (01) ◽  
pp. 143-160 ◽  
Author(s):  
Meng-Jie Wang ◽  
Chun-Hua Yang ◽  
Yue Jin ◽  
Chang-Biao Wan ◽  
Wei-He Qian ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Viral Replication ◽  
Lipid Content ◽  
Hela Cells ◽  
Lipid Synthesis ◽  
Heart Weight ◽  
Mrna Levels ◽  
Cellular Lipid ◽  
Autophagosome Formation ◽  
Cvb3 Infection

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.

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