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.

THE BIOSYNTHESIS OF LONG-CHAIN FATTY ACIDS IN THE DEVELOPING CASTOR BEAN

1965 ◽  
Vol 43 (1) ◽  
pp. 49-62 ◽  
Author(s):  
D. T. Canvin
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Ricinoleic Acid ◽  
Castor Bean ◽  
Diethyl Malonate ◽  
Water Soluble ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

Acetate-1-C14 and acetate-2-C14 were supplied to slices of developing castor bean endosperm. The molecules were extensively incorporated into long-chain fatty acids, water-soluble compounds, and protein. Oleic acid was the fatty acid initially labelled from acetate and it was the precursor of ricinoleic acid. Aerobic conditions were required for the formation of oleic acid and for the conversion of oleic acid to ricinoleic acid. Under anaerobic conditions the incorporation of acetate carbon into fatty acids was inhibited more than 90% and almost all of the C14 was found in stearic and palmitic acids. Stearic acid appeared to be formed first and palmitic acid appeared to be derived from it through a shortening of the chain. The position of linoleic acid in the fatty acid interconversions was not clear except that it was not a free intermediate in the conversion of oleic acid to ricinoleic acid.Malonate-C14 was only absorbed slightly by the tissue and although absorption could be increased by the use of diethyl malonate the metabolism of the compound was not facilitated. Because of its poor utilization by the tissue the role of malonate in long-chain fatty acid synthesis in this tissue could not be ascertained.

scholarly journals Polyenoic very-long-chain fatty acids mobilize intracellular calcium from a thapsigargin-insensitive pool in human neutrophils. The relationship between Ca2+ mobilization and superoxide production induced by long- and very-long-chain fatty acids

1995 ◽  
Vol 311 (2) ◽  
pp. 689-697 ◽  
Author(s):  
S J Hardy ◽  
B S Robinson ◽  
A Ferrante ◽  
C S T Hii ◽  
D W Johnson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Chain Length ◽  
Carbon Chain ◽  
Superoxide Production ◽  
Human Neutrophils ◽  
Carbon Chain Length ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

Fatty acids with more than 22 carbon atoms (very-long-chain fatty acids; VLCFAs) are normal cellular components that have been implicated in the pathophysiology of a number of peroxisomal disorders. To date, however, essentially nothing is known regarding their biological activities. Ca2+ mobilization is an important intracellular signalling system for a variety of agonists and cell types. Given that several polyunsaturated long-chain fatty acids mobilize intracellular Ca2+ and that we have postulated that the VLCFAs may be involved in signal transduction, we examined whether the tetraenoic VLCFA induced Ca2+ mobilization in human neutrophils. We report that fatty acid-induced intracellular Ca2+ mobilization declined for fatty acid species of more than 20 carbon atoms, but increased again as the carbon chain length approached 30. This Ca2+ mobilization occurred independently of inositol 1,4,5-triphosphate production and protein kinase C translocation and involved both the release of Ca2+ from the intracellular stores and changes to the influx or efflux of the ion. We further observed that triacontatetraenoic acid [30:4(n-6)] mobilized Ca2+ from a thapsigargin-insensitive intracellular pool distinct from the thapsigargin-sensitive pools affected by arachidonic acid [20:4(n - 6)] or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). 20:4 (n - 6) induced strong superoxide production (chemiluminescence) which was inhibited by thapsigargin pretreatment. In contrast, fatty acid-induced superoxide production progressively declined as the carbon chain length increased beyond 20-22 carbon atoms. Further studies suggested that the thapsigargin-insensitive Ca2+ mobilization elicited by 30:4 (n - 6) was not related to oxyradical formation, while the thapsigargin-sensitive Ca2+ mobilization induced by 20:4 (n - 6) may be involved in the initiation but not necessarily the maintenance of superoxide production. In conclusion, this is the first report to demonstrate a biological activity for the VLCFA and indicates that 30:4 (n - 6) influences second messenger systems in intact cells that differ from those affected by long-chain fatty acids such as 20:4 (n - 6).

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 Structure and lipid distribution of polyenoic very-long-chain fatty acids in the brain of peroxisome-deficient patients (Zellweger syndrome)

1987 ◽  
Vol 248 (1) ◽  
pp. 61-67 ◽  
Author(s):  
P Sharp ◽  
A Poulos ◽  
A Fellenberg ◽  
D Johnson
Keyword(s):  
Fatty Acids ◽  
Neutral Lipids ◽  
Zellweger Syndrome ◽  
Carbon Chain ◽  
Chain Elongation ◽  
Normal Brain ◽  
Long Chain Fatty Acids ◽  
Beta Oxidation ◽  
Long Chain ◽  
Chain Fatty Acids

The polyenoic fatty acids with carbon chain lengths from 26 to 38 (very-long-chain fatty acids, VLCFA) previously detected in abnormal amounts in Zellweger syndrome brain have been shown to be n-6 derivatives and therefore probably derived by chain elongation of shorter-chain n-6 fatty acids such as linoleic acid and arachidonic acid. Polyenoic VLCFA are also present in Zellweger syndrome liver, but this tissue differs significantly from brain in that the saturated and mono-unsaturated derivatives are the major VLCFA. Zellweger syndrome brain polyenoic VLCFA are present in the neutral lipids predominantly in cholesterol esters, with smaller amounts in the non-esterified fatty acid and triacylglycerol fractions. These fatty acids are barely detectable in any of the major phospholipids, but are present in significant amounts in an unidentified minor phospholipid. The polyenoic VLCFA composition of this lipid differs markedly from that observed for all other lipids, as it contains high proportions of pentaenoic and hexaenoic fatty acids with 34, 36 and 38 carbon atoms. A polar lipid with the chromatographic properties in normal brain contains similar fatty acids. It is postulated that the polyenoic VLCFA may play an important role in normal brain and accumulate in Zellweger syndrome brain because of a deficiency in the peroxisomal beta-oxidation pathway, although a possible peroxisomal role in the control of carbon-chain elongation cannot be discounted.

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.

In vivo study of the biosynthesis of long-chain fatty acids using deuterated water

1995 ◽  
Vol 269 (2) ◽  
pp. E247-E252 ◽  
Author(s):  
H. O. Ajie ◽  
M. J. Connor ◽  
W. N. Lee ◽  
S. Bassilian ◽  
E. A. Bergner ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Chain Elongation ◽  
Deuterated Water ◽  
De Novo Synthesis ◽  
Isotopomer Distribution ◽  
Long Chain ◽  
Mass Isotopomer

To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass isotopomer distribution analysis in hairless mice and Sprague-Dawley rats. Animals were given 4% deuterated water for 5 days or 8 wk in their drinking water. Blood was withdrawn at the end of these times for the determination of deuterium enrichment, and the animals were killed to isolate the various tissues for lipid extraction for the determination of the mass isotopomer distributions. The mass isotopomer distributions in LCFA were incompatible with synthesis from a single pool of primer. The synthesis of palmitate, stearate, arachidate, behenate, and lignocerate followed the expected biochemical pathways for the synthesis of LCFAs. On average, three deuterium atoms were incorporated for every addition of an acetyl unit. The isotopomer distribution resulting from chain elongation and de novo synthesis can be described by the linear combination of two binomial distributions. The proportions of preexisting, chain elongation, and de novo-synthesized fatty acids as a percentage of the total fatty acids were determined using multiple linear regression analysis. Fractional synthesis was found to vary, depending on the tissue type and the fatty acid, from 47 to 87%. A substantial fraction (24-40%) of the newly synthesized molecules was derived from chain elongation of unlabeled (recycled) palmitate.

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.

Caprenin 1. Digestion, Absorption, and Rearrangement in Thoracic Duct-Cannulated Rats

1991 ◽  
Vol 10 (3) ◽  
pp. 325-340 ◽  
Author(s):  
D. R. Webb ◽  
R. A. Sanders
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Female Rats ◽  
Acid Uptake ◽  
Long Chain Fatty Acids ◽  
Male And Female ◽  
Medium Chain ◽  
Male And Female Rats ◽  
Long Chain ◽  
Chain Fatty Acids

Caprenin (CAP) is a triglyceride that primarily contains caprylic (C8:0), capric (C10:0), and behenic (C22:0) acids. This study was undertaken to determine whether or not CAP is qualitatively digested, absorbed, and rearranged like other dietary fats and oils that contain these medium-chain and very long-chain fatty acids. In vitro results showed that neat CAP, coconut oil (CO) and peanut oil (PO) were hydrolyzed by porcine pancreatic lipase. All of the neat triglycerides also were digested in vivo by both male and female rats. This was shown by the recovery of significantly more extractable lymphatic fat than with fat-free control animals and by the recovery of orally administered triglyceride-derived fatty acids in lymph triglycerides. However, substantially more PO (74%) and CO (51%) were recovered in lymph relative to CAP (10%). These quantitative differences are consistent with the fatty acid composition of each triglyceride and primary routes of fatty acid uptake. The 24-h lymphatic recovery of CAP-derived C8:0, C10:0, and C22:0 averaged 3.9%, 17.8%, and 11.2%, respectively, for male and female rats. The C8:0 and C10:0 results approximated those obtained with CO (2.0% and 16.3%, respectively). In contrast, the 24-h absorbability of C22:0 in CAP was significantly less than that seen in PO (55.4%). Finally, there was no evidence of significant rearrangement of the positions of fatty acids on glycerol during digestion and absorption. Those fatty acids recovered in lymphatic fat tended to occupy the same glyceride positions that they did in the neat administered oils. However, the lymph fats recovered from all animals dosed with fat emulsions were enriched with endogenous lymph fatty acids. It is concluded that CAP is qualitatively digested, absorbed, and processed like any dietary fat or oil that contains medium-chain and very long-chain fatty acids.

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