Biosynthesis of polyunsaturated fatty acids from the linoleic acid family in cultured cells.
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Arachidonic Acids↗
Biomedical subjects
R R Brenner
Publications and source records attributed to R R Brenner.
Regulatory function of delta6 desaturate -- key enzyme of polyunsaturated fatty acid synthesis.
The delta6 desaturation of unsaturated acyl-CoA is the first reaction involved in the normal biosynthesis of all polyunsaturated fatty acids families in animal microsomes. Due to this key position it can regulate the biosynthesis of the fatty acids of the series. The reaction is modified by competition with substrates and products, ATP, and acyl-CoA acceptors. Dietary glucose and fructose inhibit the enzyme whereas protein diets and essential fatty acid deficient diets enhance the reaction independently of hormonal effects. The enzyme is sensitive to hormones concentration. Insulin enhance the reaction but the effect is eliminated by protein synthesis inhibition. Hyperglucemic hormones as glucagon, and epinephrine depress the activity of the delta6 desaturase by reactions triggers by an increase of cAMP concentration. The lateral relation of linoleic or alpha-linolenic microsomal elongation is insensitive to insulin, glucagon, epinephrine and protein. All these effects have been proved by either in vivo experiments or cell culture using linoleic or alpha-linolenic acids as substrates.
Animals↗
Lipid metabolism of the yellow clam, Mesodesma mactroides: 3-saturated fatty acids and acetate metabolism.
The fate of labeled palmitate, stearate, and acetate administered to the yellow clam, Mesodesma mactroides, was investigated. 1(-14)C palmitic and 1(-14)C stearic acids were oxidized to CO2 to a limited extent. They were mainly incorporated in diacylglycerols and triacylglycerols and were converted to higher homologs. After administration, palmitic acid was converted to stearic and oleic acids, whereas administered stearic acid was converted to 18:1, 18:2, 20:1, and 20:2 acids. Labeled acetate was readily included by the clam in 12:0, 14:0, 14:1, 15:0, 16:1, 16:1, 16:2, 18:2, 18:1, 18:2, 20:1, 20:2, and 20:3 acids.
Acetates↗
Effect of polyunsaturated fatty acids of the alpha-linolenic series on the development of rat testicles.
The effect of 22:6 omega 3 acid provided by dietary fish oil on the development of germinal tissue of rat testes, fatty acid composition of lipids, and linoleic or alpha-linolenic acid delta 6 desaturation capacity was investigated. Results were compared to those obtained in animals fed methyl palmitate and sunflower seed oil (linoleate). At 7 and 9 weeks of age, development of germinal tissue of animals fed fish oil was normal. The fatty acid composition showed a decrease in 22:5 omega 6 acid content and an increase in 22:6 omega 3 acid in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. The fatty acid delta 6 desaturation capacity of testicules microsomes was increased. It is suggested that 22:6 omega 3 acid may functionally replace 22:5 omega 6 acid in germinal tissue.
Aging↗
Metabolism of endogenous substrates by microsomes.
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Animals↗
Effect of thyroxine on delta 6 and delta 9 desaturation activity.
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Animals↗
Comparative fatty acid composition of lipids from tubular and interstitial cells of rat testicles.
Leydig cells and tubules of rat testes were separated by a gentle procedure. The fatty acid composition of each fraction was analyzed by gas liquid chromatography. The fraction containing the interstitial tissue was richer in myristic, palmitoleic, stearic, oleic and linoleic acids whereas tubules contained more palmitic, arachidonic, and docosa-4,7,10,13,16-pentaenoic acid. The specific predominance of docosa-4,7,10,13,16-pentaenoic acid in tubules stresses the possible vital importance of this acid in germinal cells. Aldehydes of 14,16 and 18 carbons derived from alkenyl-glyceryl ethers were recognized in both fractions.
Aldehydes↗
Effect of different carbon sources on the biosynthesis of polyunsaturated fatty acids of alpha-linolenic acid family in culture of minimal deviation hepatoma 7288 C cells.
The effect of three different carbon sources on the biosynthesis of polyunsaturated fatty acids of the alpha-linolenic acid series was investigated in hepatoma tissue culture (HTC) cells. Alpha linolenic acid was converted to higher homologs by a desaturating route that synthetized mainly 18:4 (delta6, 9, 12, 15), 20:4 (delta8, 11, 14, 17) and 20:5 (delta5, 8, 11, 14, 17) and an elongating route that produced 20:3 (delta11, 14, 17) and 20:4 (delta5, 11, 14, 17) acids. "Fasting" decreased both biosynthetic routes whereas glucose reactivated only the elongating pathway. Lactabumin hydrolysate enhanced significantly only the desaturating route whereas glycerol was inactive. Glucose and aminoacids increased similarly the incorporation of labeled alpha linolenic acid in the cells. The results are independent of hormonal effects.
Carcinoma, Hepatocellular↗
The action of insulin and dibutyryl cyclic AMP on the biosynthesis of polyunsaturated acids of alpha-linolenic acid family in HTC cells.
Incubation of HTC cells (7288 C) with 114C-alpha-linolenic acid in Swim's 77 medium during 24 hours converted the fatty acid to octadeca-6,9,12,15-tetraenoic acid, eicosa-11,14,17-trienoic acid, eicosa-8,11,14,17-tetraenoic acid, eicosa-5,11,14,17-tetraenoic acid, eicosa-5,8,11,14,17-pentaenoic acid and unsaturated acids of 22 carbons. The existence of two pathways was recognized: one initiated by a delta6-desaturation and the other by an elongation of alpha-linolenic acid. Incubation of the cells with insulin and dibutyryl cyclic AMP modified both pathways in different ways. HTC cells were sensitive to insulin which enhanced the desaturating route increasing eicosapentaenoic acid synthesis and depressed the elongating route decreasing eicosatrienoic acid. In an opposite way, dibutyryl cyclic AMP decreased eicosapentaenoic acid synthesis and increased eicosatrienoic acid.
Bucladesine↗
Linoleic acid desaturation activity of liver microsomes of essential fatty acid deficient and sufficient rats.
Studies were carried out to relate the changes of the fatty acid and lipid composition of rat microsomes with the modification of the activity of the linoleic acid desaturation evoked by an essential fatty acid deficient diet. Two steps were shown in the progression of the essential fatty acid deficienty. In a first step shown at three days of essential fatty acid deficiency the fatty acid composition was changed by decreasing linoleic and arachidonic acids and increasing oleic and eicosatrienoic (-9) acids. No change was found in the lipid distribution and approximate V and Km of the linoleic acid desaturation. In this first step the unsaturated/saturated fatty acids ratio fell in spite of the synthesis of eicosatrienoic (n-9) acid that was produced without any change of enzyme activity. In a second step shown at 15 days of essential fatty acid deficiency the change of the fatty acid composition was greater but the unsaturated/saturated acid ratio was restored. An increase of triacylglycerols and a decrease of phospholipids was also detected together with an enhanced activity of linoleic acid desaturation (higher approximate V) and a higher approximate Km. The increase of the V of linoleic acid desaturation is considered to be evoked by an increased level of active delta-6 desaturase. The increased activity of the delta-6 desaturase in this second period is a secondary and important response of the cell to maintain the unsaturated : saturated acid ratio and fluidity of the membrane.
Animals↗
Influence of environmental temperature on the fatty acid desaturation and elongation activity of fish (Pimelodus maculatus) liver microsomes.
The effect of environmental temperature on the activity of liver microsomes of fish (Pimelodus maculatus) to desaturate and elongate oleic, linoleic and alpha-linolenic acids was studied. It was found that: 1. Fish kept at 14-15 degrees C had higher desaturation and elongation activity than animals kept at 29-30 degrees C. The ratio of activity was the same for the three fatty acids. 2. A decrease of the environmental temperature increased the V of linoleic acid desaturation to gamma-linolenic acid, but did not modify the approximate Km of the reaction. 3. The inactivation of the delta6-desaturase of microsomes separated from fish kept at 29-30 degrees C and 14-15 degrees C was the same when heated at 40 degrees C. However, the enzyme was deactivated faster when heated at 29-30 degrees C than at 14-15 degrees C. 4. The increase of the delta6-desaturation activity of the microsomes evoked by the decrease of the temperature of the aquarium was mostly compensated for by the correlative decrease of the specific reaction rate of the reaction. For this reason it is assumed that the adaptive change of the desaturation activity of the microsomes with the environmental temperature does not greatly modify the fatty acid composition of the fish.
Animals↗
Lipid metabolism of the yellow clam, Mesodesma mactroides: 2-polyunsaturated fatty acid metabolism.
The fate of labeled linoleic, alpha-linolenic, and higher homologs of alpha-linolenic acid administered to the yellow clam, Mesodesma mactroides, was investigated. It was found that the clam incorporated the acids dissolved in sea water and converted 18:2 (n-6) into 20:2 (n-6) and 18:3 (n-3) into 18:4 (n-3) and 20:3 (n-3). The addition of casein hydrolysate to the sea water increased the desaturation capacity of the calm and allowed the conversion of 18:2 (n-6) into 18:3 (n-6) to be demonstrated. An enhanced desaturation of 18:3 (n-3) into 18:4 (n-3) was also demonstrated. After 12 hr admininistration of the acid, no radioactivity was found in arachidonic, 20:5 (n-3), or 22:6 (n-3). Feeding the clams a culture of Phaeodactylun tricornutum previously incubated with 1-14C-alph-linolenic acid demonstrated that all the homologs of the alpha-linolenic series were found in the clam without any important changes. Six hour administration of labled linolenic acid resulted in the incorporation of the acid into diglycerides and phospholipids.
Animals↗
Comparative effect of glucagon, dibutyryl cyclic AMP, and epinephrine on the desaturation and elongation of linoleic acid by rat liver microsomes.
The effect of glucagon, dibutyryl cyclic adenosine 3',5'-monophosphate, and epinephrine on the biosynthesis of polyunsaturated fatty acids of the linoleic acid family was studied. The incubations were performed with rat liver microsomes and labeled linoleic acid under desaturating and elongating conditions. Under desaturating conditions linoleic acid was converted to gamma-linolenic acid, whereas under elongating conditions it was converted to 20:2omega6. Glucagon, dibutyryl cyclic AMP, and epinephrine decreased the oxidative desaturation of linoleic acid to gamma-linolenic acid while the elongating reaction was not modified in the experimental conditions tested. Consequently, the results support the hypothesis that the oxidative desaturation of linoleic acid to gamma-linolenic acid is the main controllable step in the biosynthesis of polyunsaturated fatty acids of the linoleic acid family in the microsomes.
Animals↗
Fatty acid biosynthesis during embryogenesis in the amphibian Bufo arenarum Hensel.
The fatty acid composition and biosynthesis of fatty acids were studied during early embryogenesis of the toad Bufo arenarum Hensel. The ova and stages up to the 6 1/2 day embryo have similar fatty acid compositions, with ca. 70% unsaturated acids. The eggs and embryo were permeable to acetate and impermeable to palmitic, linoleic, and eicosa-8, 11, 14-trienoic acid. Labeled acetate was incorporated by the eggs into the saturated acids-lauric, myristic, palmitic, stearic, arachidic, and behenic- and into the unsaturated acids-myristoleic, palmitoleic, oleic, and eicosaenoic acids. During segmentation and gastrulation, de novo biosynthesis of fatty acids increased, desaturation to myristoleic, palmitoleic, and oleic acids was enhanced; and fatty acids were esterified to triglycerides, phosphatidyl choline, and phosphatidyl ethanolamine. The feeding embryo (11 days) changed the pattern of incorporation to less incorporation into triglycerides.
8,11,14-Eicosatrienoic Acid↗
Lipid metabolism of the yellow clam, Mesodesma mactroides: I. Composition of the lipids.
The lipid composition of the yellow clam, Mesodesma mactroides, that lives in the northern beaches of the Buenos Aires province of Argentina was studied. The main nonpolar lipids are triglycerides and alkoxyglycerides. Phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl serine are the main phospholipids. The predominant fatty acids are 16:0, 16:1omega7, 18:0, 18:1omega9, 20:5omega3, and 22:6omega3. They are mainly provided by the clam's food and stored in the hepatopancreas. The content of polyunsaturated acids increases in summer together with an increase in nonpolar lipids and is correlative with an increase in phytoplankton in the sea water. Sexual maturity modifies the lipid composition of gametes.
Animals↗
[Essential fatty acids and their transformations in the animals (author's transl)].
The research of essential fatty acids biochemistry in Argentina was initiated approximately twenty years ago. These investigations together with the outstanding findings obtained in other countries proved the existence of different types of reactions. The essential fatty acids, linolenic and alpha linolenic, are converted by desaturation and elongation reactions in higher homologs building families of fatty acids. These reactions are regulated by dietary components, hormones, temperature and products of reaction. Retroconversion reactions transform the higher homologs, especially of 22 carbons back again to lower homologs avoiding beta oxidation. They are incorporated in the lipids to build the lipoproteic membranes increasing their fluidity. Specific acids are converted to prostaglandins that function as specific hormones.
Animals↗
Effect of epinephrine on the oxidative desaturation of fatty acids in the rat.
The effect of epinephrine on the oxidative desaturation of fatty acids by liver microsomal preparations of rats has been studied. Administration of epinephrine (1 mg/kg body weight) produced a significant decrease in desaturation of [l-14C]=linoleic acid to gamma-linolenic acid and of [L-14C]alpha-linolenic acid to actadeca-6,9,12,15-tetraenoic acid 12 hr after the infection. Lower doses produced a lesser effect on the delta6-desaturation activity. Epinephrine administration modified the V max of linoleic acid desaturation but not the K m. There was also a slight increase in palmityl desaturation activity. The effect of epinephrine on delta6-desaturation activity was postulated to be mediated through an enhancement of the intracellular cyclic AMP levels that lead to an increase of a glucose metabolite. This metabolite would inhibit delta6-desaturation activity.
Animals↗
Separation of a protein factor necessary for the oxidative desaturation of fatty acids in the rat.
Microsomes from rat liver were extracted by low ionic strength solutions. Extracted microsomes lost most of the linoleic acid desaturation activity. The addition of the extract back into the extracted microsomes was necessary to restore full desaturation activity. The soluble fraction had no desaturation activity. The existence of a soluble factor loosely bound to the microsomes, stable to sonication, and unstable to heat and trypsin digestion was recognized. This protein could not be replaced by albumin. The factor was also essential for the oxidative desaturation of palmitic, stearic, linoleic, and gamma-linolenic acid. The present experiment suggests that the protein factor is not NADH-cytochrome b5 reductase, cytochrome b5, or the cyanide-sensitive factor.
Animals↗