scholarly journals Targeting of Tsc13p to Nucleus–Vacuole Junctions: A Role for Very-Long-Chain Fatty Acids in the Biogenesis of Microautophagic Vesicles

2005 ◽  
Vol 16 (9) ◽  
pp. 3987-3998 ◽  
Author(s):  
Erik Kvam ◽  
Kenneth Gable ◽  
Teresa M. Dunn ◽  
David S. Goldfarb
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Acid Synthesis ◽  
Dependent Manner ◽  
Long Chain Fatty Acids ◽  
Vacuole Membrane ◽  
Mutant Cells ◽  
Long Chain ◽  
Chain Fatty Acids

TSC13 is required for the biosynthesis of very-long-chain fatty acids (VLCFAs) in yeast. Tsc13p is a polytopic endoplasmic reticulum (ER) membrane protein that accumulates at nucleus–vacuole (NV) junctions, which are formed through Velcro-like interactions between Nvj1p in the perinuclear ER and Vac8p on the vacuole membrane. NV junctions mediate piecemeal microautophagy of the nucleus (PMN), during which bleb-like portions of the nucleus are extruded into invaginations of the vacuole membrane and degraded in the vacuole lumen. We report that Tsc13p is sequestered into NV junctions from the peripheral ER through Vac8p-independent interactions with Nvj1p. During nutrient limitation, Tsc13p is incorporated into PMN vesicles in an Nvj1p-dependent manner. The lumenal diameters of PMN blebs and vesicles are significantly reduced in tsc13-1 and tsc13-1 elo3-Δ mutant cells. PMN structures are also smaller in cells treated with cerulenin, an inhibitor of de novo fatty acid synthesis and elongation. The targeting of Tsc13p-GFP into NV junctions is perturbed by cerulenin, suggesting that its binding to Nvj1p depends on the availability of fatty acid substrates. These results indicate that Nvj1p retains and compartmentalizes Tsc13p at NV junctions and that VLCFAs contribute to the normal biogenesis of trilaminar PMN structures in yeast.

Chloroacetamide Mode of Action, I: Inhibition of Very Long Chain Fatty Acid Synthesis in Scenedesmus acutus

1998 ◽  
Vol 53 (11-12) ◽  
pp. 995-1003 ◽  
Keyword(s):  
Fatty Acids ◽  
Cell Wall ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Acid Synthesis ◽  
Resistant Cell Line ◽  
Long Chain Fatty Acids ◽  
Scenedesmus Acutus ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Herbicidal chloroacetamides cause a very sensitive inhibition of fatty acid incorporation into an insoluble cell wall fraction of Scenedesmus acutus. The molecular basis was investigated in more detail. After incubation of the algae with [14C]oleic acid and saponification, the remaining pellet was solubilized and fractionated consecutively with chloroform / methanol, phosphate buffer, amylase, pronase, and finally with dioxane/HCl. By acid hydrolysis in dioxane a part of the cell wall residue was solubilized showing inhibition of exogenously applied oleic acid and other labelled precursors such as stearic acid, palmitic acid, and acetate. After extraction of this dioxane-soluble subfraction with hexane, HPLC could separate labelled metabolites less polar than oleic acid. T heir formation was completely inhibited by chloroacetam ides, e.g. 1 μᴍ metazachlor. This effect was also observed with the herbicidally active 5-enantiomer of metolachlor while the inactive R-enantiomer had no influence. These strongly inhibited metabolites could be characterized by radio-HPLC /MS as very long chain fatty acids (VLCFAs) with a carbon chain between 20 and 26. Incubating am etazachlor-resistant cell line of S. acutus (Mz-1) with [14C]oleic acid, V LCFA s could not be detected in the dioxane/ HCl-subfraction. Furthermore, comparing the presence of endogenous fatty acids in wildtype and mutant Mz-1 the VLCFA content of the mutant is very low, while the content of long chain fatty acids (C16 -18) is increased, particularly oleic acid. Obviously, the phytotoxicity of chloroacetam ides in S. acutus is due to inhibition of VLCFA synthesis. The resistance of the mutant to metazachlor has a bearing on the higher amount of long chain fatty acids replacing the missing VLCFAs in essential membranes or cell wall components.

scholarly journals A Review of the Metabolic Origins of Milk Fatty Acids

2013 ◽  
Vol 5 (3) ◽  
pp. 270-274 ◽  
Author(s):  
Anamaria COZMA ◽  
Doina MIERE ◽  
Lorena FILIP ◽  
Sanda ANDREI ◽  
Roxana BANC ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Milk Fat ◽  
De Novo ◽  
Long Chain Fatty Acids ◽  
De Novo Synthesis ◽  
Ruminal Biohydrogenation ◽  
Long Chain ◽  
Chain Fatty Acids

Milk fat and its fatty acid profile are important determinants of the technological, sensorial, and nutritional properties of milk and dairy products. The two major processes contributing to the presence of fatty acids in ruminant milk are the mammary lipogenesis and the lipid metabolism in the rumen. Among fatty acids, 4:0 to 12:0, almost all 14:0 and about a half of 16:0 in milk fat derive from de novo synthesis within the mammary gland. De novo synthesis utilizes as precursors acetate and butyrate produced through carbohydrates ruminal fermentation and involves acetyl-CoA carboxylase and fatty acid synthetase as key enzymes. The rest of 16:0 and all of the long-chain fatty acids derive from mammary uptake of circulating lipoproteins and nonesterified fatty acids that originate from digestive absorption of lipids and body fat mobilization. Further, long-chain fatty acids as well as medium-chain fatty acids entering the mammary gland can be desaturated via Δ-9 desaturase, an enzyme that acts by adding a cis-9-double bond on the fatty acid chain. Moreover, ruminal biohydrogenation of dietary unsaturated fatty acids results in the formation of numerous fatty acids available for incorporation into milk fat. Ruminal biohydrogenation is performed by rumen microbial population as a means of protection against the toxic effects of polyunsaturated fatty acids. Within the rumen microorganisms, bacteria are principally responsible for ruminal biohydrogenation when compared to protozoa and anaerobic fungi.

scholarly journals Identification and biophysical characterization of a very-long-chain-fatty-acid-substituted phosphatidylinositol in yeast subcellular membranes

2004 ◽  
Vol 381 (3) ◽  
pp. 941-949 ◽  
Author(s):  
Roger SCHNEITER ◽  
Britta BRÜGGER ◽  
Clare M. AMANN ◽  
Glenn D. PRESTWICH ◽  
Raquel F. EPAND ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Analysis ◽  
Hexagonal Phase ◽  
Acid Synthesis ◽  
Long Chain Fatty Acids ◽  
Biophysical Properties ◽  
Ceramide Synthesis ◽  
Long Chain ◽  
Chain Fatty Acids

Morphological analysis of a conditional yeast mutant in acetyl-CoA carboxylase acc1ts/mtr7, the rate-limiting enzyme of fatty acid synthesis, suggested that the synthesis of C26 VLCFAs (very-long-chain fatty acids) is important for maintaining the structure and function of the nuclear membrane. To characterize this C26-dependent pathway in more detail, we have now examined cells that are blocked in pathways that require C26. In yeast, ceramide synthesis and remodelling of GPI (glycosylphosphatidylinositol)-anchors are two pathways that incorporate C26 into lipids. Conditional mutants blocked in either ceramide synthesis or the synthesis of GPI anchors do not display the characteristic alterations of the nuclear envelope observed in acc1ts, indicating that the synthesis of another C26-containing lipid may be affected in acc1ts mutant cells. Lipid analysis of isolated nuclear membranes revealed the presence of a novel C26-substituted PI (phosphatidylinositol). This C26-PI accounts for approx. 1% of all the PI species, and is present in both the nuclear and the plasma membrane. Remarkably, this C26-PI is the only C26-containing glycerophospholipid that is detectable in wild-type yeast, and the C26-substitution is highly specific for the sn-1 position of the glycerol backbone. To characterize the biophysical properties of this lipid, it was chemically synthesized. In contrast to PIs with normal long-chain fatty acids (C16 or C18), the C26-PI greatly reduced the bilayer to hexagonal phase transition of liposomes composed of 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE). The biophysical properties of this lipid are thus consistent with a possible role in stabilizing highly curved membrane domains.

scholarly journals Metabolism of saturated and polyunsaturated very-long-chain fatty acids in fibroblasts from patients with defects in peroxisomal β-oxidation

1990 ◽  
Vol 269 (3) ◽  
pp. 671-677 ◽  
Author(s):  
J M Street ◽  
H Singh ◽  
A Poulos
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Normal Skin ◽  
Carbon Chain ◽  
Water Soluble ◽  
Chain Elongation ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

The metabolism of [1-14C]lignoceric acid (C24:0) and [1-14C]tetracosatetraenoic acid (C24:4, n-6) was studied in normal skin fibroblast cultures and in cultures from patients with defects in peroxisomal β-oxidation (but normal peroxisomal numbers). Cells from X-linked adrenoleukodystrophy (ALD) patients with a presumed defect in a peroxisomal acyl-CoA synthetase, specific for fatty acids of carbon chain lengths greater than 22 (very-long-chain fatty acids; VLCFA), showed a relatively normal production of radiolabelled CO2 and water-soluble metabolites from [1-14C]C24:0. However, the products of synthesis from acetate de novo (released by β-oxidation), i.e. C16 and C18 fatty acids, were decreased, and carbon chain elongation of the fatty acid was increased. In contrast, cell lines from two patients with an unidentified lesion in peroxisomal β-oxidation (peroxisomal disease, PD) showed a marked deficiency in CO2 and water-soluble metabolite production, a decreased synthesis of C16 and C18 fatty acids and an increase in carbon chain elongation. The relatively normal β-oxidation activity of ALD cells appears to be related to low uptake of substrate, as a defect in β-oxidation is apparent when measurements are performed on cell suspensions under high uptake conditions. Oxidation of [1-14C]C24:4 was relatively normal in ALD cells and in the cells from one PD patient but abnormal in those from the other. Our data suggest that, despite the deficiency in VLCFA CoA synthetase, ALD cells retain a near normal ability to oxidize both saturated and polyunsaturated VLCFA under some culture conditions. However, acetate released by β-oxidation of the saturated VLCFA and, to a much lesser degree, the polyunsaturated VLCFA, appears to be used preferentially for the production of CO2 and water-soluble products, and acetate availability for fatty acid synthesis in other subcellular compartments is markedly decreased. It is likely that the increased carbon chain elongation of the saturated VLCFA which is also observed reflects the increased availability of substrate (C24:0) and/or an increase in microsomal elongation activity in ALD cells.

scholarly journals Interactions of insulin, corticosterone and prolactin in promoting milk-fat synthesis by mammary explants from pregnant rabbits

1972 ◽  
Vol 129 (4) ◽  
pp. 929-935 ◽  
Author(s):  
Isabel A. Forsyth ◽  
Christopher R. Strong ◽  
Raymond Dils
Keyword(s):  
Fatty Acids ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Long Chain ◽  
Chain Fatty Acids

1. The rate of fatty acid synthesis by mammary explants from rabbits pregnant for 16 days or from rabbits pseudopregnant for 11 days was stimulated up to 15-fold by culturing for 2–4 days with prolactin. This treatment initiated the predominant synthesis of C8:0 and C10:0 fatty acids, which are characteristic of rabbit milk. 2. Inclusion of insulin in the culture medium increased the rate of synthesis of these medium-chain fatty acids. By contrast the inclusion of corticosterone led to the predominant synthesis of long-chain fatty acids. When explants were cultured for 2–4 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased up to 42-fold, but both medium- and long-chain fatty acids were synthesized. 3. These results show that the stimulus to mammary-gland lipogenesis and the initiation of synthesis of medium-chain fatty acids observed between days 16 and 23 of pregnancy in the rabbit can be simulated in vitro by prolactin alone. 4. When mammary explants from rabbits pregnant for 23 days were cultured for 2 days with insulin, corticosterone and prolactin, the rate of fatty acid synthesis increased fivefold, but there was a preferential synthesis of long-chain fatty acids. Culture with prolactin alone had little effect on the rate or pattern of fatty acids synthesized. 5. The results are compared with findings in vivo on the control of lipogenesis in the rabbit mammary gland, and are contrasted with the known effects of hormones in vitro on the mammary gland of the mid-pregnant mouse.

scholarly journals Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Fatty Acid ◽  
Liver Injury ◽  
Olive Oil ◽  
Coconut Oil ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

Effects of cold acclimation on lipid metabolism in adipose tissue

1961 ◽  
Vol 200 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Judith K. Patkin ◽  
E. J. Masoro
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cold Acclimation ◽  
Long Chain Fatty Acids ◽  
Synthetic Capacity ◽  
And Control ◽  
Long Chain ◽  
Chain Fatty Acids

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.

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