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1.
Which cell type is responsible for the high levels of very long chain polyunsaturated fatty acids in testis and whether this
fatty acid pattern is a result of a local synthesis are not presently known. In this study, fatty acid conversion from 20∶4n−6
to 22∶5n−6 and from 20∶5n−3 to 22∶6n−3 was investigated in isolated rat germ cells incubated with [1-14C]-labeled fatty acids. The germ cells elongated the fatty acids from 20- to 22-carbon atoms and from 22- to 24-carbon atoms
but had a low Δ6 desaturation activity. Thus, little [14C]22∶5n−6 and [14C]22∶6n−3 were synthesized. When Sertoli cells were incubated with [1-14C]20∶5n−3 for 24 h, an active fatty acid elongation and desaturation were observed. In vivo germ cells normally have a higher content of 22∶5n−6 or 22∶6n−3 than Sertoli cells. An eventual transport of essential fatty
acids from Sertoli cells to germ cells was thus studied. Different co-culture systems were used in which germ cells were on
one side of a filter and Sertoli cells on the opposite side. When isolated pachytene spermatocytes or round spermatids were
added to the opposite side of a semipermeable filter, approximately 1 nmol [14C]-22∶6n−3 crossed the filter. Little of this was esterified in the germ cells. Similarly, in using [1-14C]20∶4n−6 in identical experiments, very little [14C]22∶5n−6 was esterified in germ cells on the opposite side of the filter. Although the very active synthesis of 22∶5n−6 and
22∶6n−3 observed in Sertoli cells suggests a transport of these compounds to germ cells, this was not experimentally determined. 相似文献
2.
Recent research in various biological systems has revived interest in interactions between the (n−6) and (n−3) essential fatty
acids. We have utilized cultured glioma cells to show that linolenic acid, 18∶3(n−3), is rapidly desaturated and chain elongated;
20∶5(n−3) is the major product and accumulates almost exclusively in phospholipids. We examined effects of various (n−6),
(n−3), (n−9) and (n−7) fatty acids at 40 μM concentration on desaturation and chain elongation processes using [1-14C]18∶3(n−3) as substrate. In general, monoenoic fatty acids were without effect. The (n−6) fatty acids (18∶2, 18∶3, 20∶3,
20∶4 and 22∶4) had little effect on total product formed. There was a shift of labeled product to triacylglycerol, and in
phospholipids, slightly enhanced conversion of 20∶5 to 22∶5 was evident. In contrast, 22∶6(n−3) was inhibitory, whereas 20∶3(n−3)
and 20∶5(n−3) had much less effect. At concentrations <75 μM, all acids were inhibitory. Most products were esterified to
phosphatidylcholine, but phosphatidylethanolamine also contained a major portion of 20∶5 and 22∶5. We provide a condensed
overview of how the (n−6) and (n−3) fatty acids interact to modify relative rates of desaturation and chain elongation, depending
on the essential fatty acid precursor. Thus, the balance between these dietary acids can markedly influence enzymes providing
crucial membrane components and substrates for biologically active oxygenated derivatives. 相似文献
3.
Jen-sie Tou 《Lipids》1986,21(5):324-327
Docosahexaenoic acid was not only acylated into phospholipids but also into triacylglycerols by intact human neutrophils.
The distribution of radiolabeled docosahexaenoic acid among individual phospholipids was dependent on the incubation time.
[1-14C]Docosahexaenoic acid at all concentrations (1 to 8 μM) was acylated mainly into phosphatidic acid after 1–2 min incubation,
and the radioactivity of phosphatidic acid started to decline after a longer period of incubation, suggesting the participation
of docosahexaenoyl-phosphatidic acid in the synthesis of other glycerolipids. It was acylated primarily into phosphatidylcholine
(PC) and phosphatidylethanolamine (PE) after a 2-hr incubation. The labeled phosphatidic acid may be rapidly deacylated and
the 22∶6(n−3) moiety is then reacylated into other lysophospholipids. The low levels of [14C]22∶6(n−3) in 1,2-diacylglycerol suggest that the deacylation-reacylation cycle may be a major pathway in the formation of
[14C]22∶6(n−3)-PC and-PE in intact neutrophils. This n−3 fatty acid was a relatively poor substrate for acylation into phosphatidyl-inositol
as compared to arachidonic acid and eicosapentaenoic acid. However, the patterns of distribution of all three polyunsaturated
fatty acids among the diacyl-and ether-linked class compositions of PC and PE were similar. These data suggest the potential
of increasing the content of docosahexaenoic acid of membrane lipids in neutrophils by dietary supplement of this fatty acid. 相似文献
4.
This study examined the effects of n−3 and n−6 polyunsaturated fatty acid alimentation on murine peritoneal macrophage phospholipids.
Mice were fed complete diets supplemented with either corn oil predominantly containing 18∶2n−6, borage oil containing 18∶2n−6
and 18∶3n−6, fish/corn oil mixture containing 18∶2n−6, 20∶5n−3 and 22∶6n−3, or fish/borage oil mixture containing 18∶2n−6,
18∶3n−6, 20∶5n−3 and 22∶6n−3. After two weeks, the fatty acid levels of glycerophosphoserines (GPS), glycerophosphoinositols
(GPI), sphingomyelin (SPH), and of the glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) phospholipid subclasses
were determined. We found that mouse peritoneal macrophage GPC contain primarily 1-0-alkyl-2-acyl (range for the dietary groups, 24.6–30.5 mol %) and 1,2-diacyl (63.2–67.2 mol %), and that GPE contains 1-O-alk-1-enyl-2-acyl (40.9–47.4 mol. %) and 1,2-diacyl (44.2–51.2 mol %) subclasses. In general, fish oil feeding increased
macrophage 20∶5n−3, 22∶5n−3 and 22∶6n−3 levels while simultaneously reducing 20∶4n−6 in GPS, GPI, GPE and GPC subclasses except
for 1-O-alk-1′-enyl-2-acyl GPC. Administration of 18∶3n−6 rich diets (borage and fish/borage mixture) resulted in the accumulation
of 20∶3n−6 (2-carbon elongation product of 18∶3n−6) in most phospholipids. In general, the novel combination of dietary 18∶3n−6
and n−3 PUFA produced the highest 20∶3n−6/20∶4n−6 phospholipid fatty acid ratios. This study demonstrates that marked differences
in the responses of macrophage phospholipid classes and subclasses exist following dietary manipulation. The reduction of
20∶4n−6, while simultaneously increasing 30∶3n−6 and n−3 PUFA levels, may be important in relation to the putative beneficial
effects of 20∶3n−6 and fish oil on macrophage eicosanoid and platelet activating factor (PAF) biosynthesis. 相似文献
5.
A method combining data on fatty acid composition into subsets is used to illustrate general relative competitive selectivities
in the metabolic and transport events that maintain fatty acid compositions in tissue lipids and to minimize differences among
tissues or species in the amount of individual fatty acids. Fatty acid compositions of triglycerides and phospholipids in
several tissues of the rat were maintained with simple relationships between the exogenous n−3 and n−6 dietary polyunsaturated
fatty acids and the endogenous n−7 and n−9 types of fatty acid. The general pattern of fatty acids in triglycerides was similar
for liver, plasma and adipose tissue, averaging about 30% as saturated acids, 67% as 16- and 18-carbon unsaturated acids and
only about 2% as 20- and 22-carbon highly unsaturated acids. The tissues maintained a linear relationship between the amount
of 18-carbon polyunsaturated fatty acids in the diet and in the tissue triglycerides, with the proportionality constant for
18∶3n−3 being 60% of that for 18∶2n−6. The total phospholipids of liver, plasma and red blood cells maintained about 45% of
the fatty acids in the form of saturated fatty acids and 20–30% as 20- and 22-carbon highly unsaturated fatty acids irrespective
of very different proportions of n−3, n−6 and n−9 types of fatty acids. In all three tissues, the 20-carbon highly unsaturated
fatty acids of the n−3, n−6 and n−9 type were maintained in a competitive hyperbolic relationship with apparent EC50 values for dietary 18∶2n−6 and 18∶3n−3 near 0.1% of dietary calories. The consistent quantitative relationships described
in this study illustrate an underlying principle of competition among fatty acids for a limited number of esterification sites.
This approach may be useful in predicting the influence of diet upon tissue levels of the substrates and antagonists of eicosanoid
biosynthesis. 相似文献
6.
Atlantic salmon post-smolts were fed diets rich in linoleic acid (sunflower oil, SO), α-linolenic acid (linseed oil, LO) or
long-chain polyunsaturated fatty acids (fish oil, FO) for a period of 12 wk. In the liver phospholipids of fish fed SO, the
levels of 18∶2n−6, 20∶2n−6, 20∶3n−6 and 20∶4n−6 were significantly elevated compared to both other treatment. In choline phospholipids
(CPL), ethanolamine phospholipids (EPL) and phosphatidylserine (PS) the levels of 22∶4n−6 and 22∶5n−6 were significantly elevated
in fish fed SO. In liver phospholipids from fish fed LO, 18∶2n−6, 20∶2n−6 and 20∶3n−6 were significantly elevated but 20∶4n−6,
22∶4n−6 and 22∶5n−6 were similar or significantly decreased compared to fish fed FO. Liver phospholipids from fish fed LO
had increased 18∶3n−3 and 20∶4n−3 compared to both other treatments while EPL and phosphatidylinositol (PI) also had increased
20∶5n−3. In fish fed LO, 22∶6n−3 was significantly reduced in CPL, PS and PI compared to fish fed FO. Broadly similar changes
occurred in gill phospholipids. Production of 12-lipoxygenase metabolites in isolated gill cells stimulated with the Ca2+-ionophore A23187 were significantly reduced in fish fed either SO or LO compared to those fed FO. However, the ratio 12-hydroxy-5,8,10,14-eicosatetraenoic
acid (12-HETE)/12-hydroxy-5,8,10,14,17-eicosapentaenoic acid (12-HEPE) was significantly elevated in stimulated gill cells
from SO-fed fish. Although mean values of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were increased in fish fed SO, they were not significantly different from those of the other two treatments. 相似文献
7.
Leonard AE Kelder B Bobik EG Chuang LT Lewis CJ Kopchick JJ Mukerji P Huang YS 《Lipids》2002,37(8):733-740
In mammalian cells, Sprecher has proposed that the synthesis of long-chain PUFA from the 20-carbon substrates involves two
consecutive elongation steps, a Δ6-desaturation step followed by retroconversion (Sprecher, H., Biochim. Biophys. Acta 1486, 219–231, 2000). We searched the database using the translated sequence of human elongase ELOVL5, whose encoded enzyme elongates
monounsaturated and polyunsaturated FA, as a query to identify the enzyme(s) involved in elongation of very long chain PUFA.
The database search led to the isolation of two cDNA clones from human and mouse. These clones displayed deduced amino acid
sequences that had 56.4 and 58% identity, respectively, to that of ELOVL5. The open reading frame of the human clone (ELOVL2)
encodes a 296-amino acid peptide, whereas the mouse clone (Elovl2) encodes a 292-amino acid peptide. Expression of these open
reading frames in baker's yeast, Saccharomyces cerevisiae, demonstrated that the encoded proteins were involved in the elongation of both 20-and 22-carbon long-chain PUFA, as determined
by the conversion of 20∶4n−6 to 22∶4n−6, 22∶4n−6 to 24∶4n−6, 20∶5n−3 to 22∶5n−3, and 22∶5n−3 to 24∶5n−3. The elongation activity
of the mouse Elovl2 was further demonstrated in the transformed mouse L cells incubated with long-chain (C20-and C22-carbon) n−6 and n−3 PUFA substrates by the significant increase in the levels of 24∶4n−6 and 24∶5n−3, respectively. This
report demonstrates the isolation and identification of two mammalian genes that encode very long chain PUFA specific elongation
enzymes in the Sprecher pathway for DHA synthesis. 相似文献
8.
Marine fish have an absolute dietary requirement for C20 and C22 highly unsaturated fatty acids. Previous studies using cultured cell lines indicated that underlying this requirement in
marine fish was either a deficiency in fatty acyl Δ5 desaturase or C18–20 elongase activity. Recent research in turbot cells found low C18–20 elongase but high Δ5 desaturase activity. In the present study, the fatty acid desaturase/elongase pathway was investigated
in a cell line (SAF-1) from another carnivorous marine fish, sea bream. The metabolic conversions of a range of radiolabeled
polyunsaturated fatty acids that comprised the direct substrates for Δ6 desaturase ([1-14C]18∶2n−6 and [1-14C]18∶3n−3), C18–20 elongase ([U-14C]18∶4n−3), Δ5 desaturase ([1-14C]20∶3n−6 and [1-14C]20∶5n−3), and C20–22 elongase ([1-14C]20∶4n−6 and [1-14C]20∶5n−3) were utilized. The results showed that fatty acyl Δ6 desaturase in SAF-1 cells was highly active and that C18–20 elongase and C20–22 elongase activities were substantial. A deficiency in the desaturation/elongation pathway was clearly identified at the level
of the fatty acyl Δ5 desaturase, which was very low, particularly with 20∶4n−3 as substrate. In comparison, the apparent activities
of Δ6 desaturase, C18–20 elongase, and C20–22 elongase were approximately 94-, 27-, and 16-fold greater than that for Δ5 desaturase toward their respective n−3 polyunsaturated
fatty acid substrates. The evidence obtained in the SAF-1 cell line is consistent with the dietary requirement for C20 and C22 highly unsaturated fatty acids in the marine fish the sea bream, being primarily due to a deficiency in fatty acid Δ5 desaturase
activity. 相似文献
9.
Because alterations in the dietary content of fatty acids are an important method for modulating macrophage eicosanoid production,
we have quantitated the levels of n−6 and n−3 polyunsaturated fatty acids in peritoneal macrophage individual phospholipids
from mice fed diets (3 wk) with either safflower oil (SAF), predominantly containing 18∶2n−6, borage (BOR) containing 18∶2n−6
and 18∶3n−6, fish (MFO) containing 20∶5n−3 and 22∶6n−3, and borage/fish mixture (MIX) containing 18∶2n−6, 18∶3n−6, 20∶5n−3
and 22∶6n−3. Dietary n−3 fattya cids were readily incorporated into macrophage phosphatidylcholine (PC), phosphatidylethanolamine
(PE), phosphatidylserine (PS) and phosphatidylinositol (PI). The increase in n−3 fatty acid levels was accompanied by a decrease
in the absolute levels of 18∶2n−6, 20∶4n−6 and 22∶4n−6 in PC, PE and PS. Interestingly, PI 20∶4n−6 levels were not significantly
lowered (P>0.05) in MIX and MFO macrophages relative to SAF and BOR. These data demonstrate the unique ability of this phospholipid
to selectively maintain its 20∶4n−6 levels. In BOR and MIX animals, 20∶3n−6 levels were significantly increased (P<0.05) in
all phospholipids relative to SAF and MFO. The combination of borage and fish oils (MIX diet) produced the highest 20∶3n−6/20∶4n−6
ratio in all phospholipids. These data show that the macrophage eicosanoid precursor levels of 20∶3n−6, 20∶4n−6 and n−3 acids
can be selectively manipulated through the use of specific dietary regimens. This is noteworthy because an increase in phospholipid
levels of 20∶3n−6 and 20∶5n−3, while concomitantly reducing 20∶4n−6, may have therapeutic potential in treating inflammatory
disorders. 相似文献
10.
Oxidation, esterification, desaturation, and elongation of [1-14C]18∶2n−6 and [1-14C]18∶3n−3 were studied using hepatocytes from Atlantic salmon (Salmo salar I.) maintained on diets deficient in n−3 and n−6 polyunsaturated fatty acids (PUFA) or supplemented with n−3 PUFA. For both
dietary groups, radioactivity from 18∶3n−3 was incoporated into lipid fractions two to three times faster than from 18∶2n−6,
and essential fatty acids (FFA) deficiency doubled the incorporation. Oxidation to CO2 was very low and was independent of substrate or diet, whereas oxidation to acid-soluble products was stimulated by EFA deficiency.
Products from 18∶2n−6 were mainly 18∶3n−6, 20∶3n−6, and 20∶4n−6, with minor amounts of 20∶2n−6 and 22∶5n−6. Products from
18∶3n−3 were mainly 18∶4n−3, 20∶5n−3, and 22∶6n−3, with small amounts of 20∶3n−3. The percentage of 22∶6n−3 in the polar lipid
fraction of EFA-deficient hepatocytes was fourfold higher than in n−3 PUFA-supplemented cells. This correlated well with our
other results obtained after abdominal injection of [1-14C]18∶3n−3 and [1-14C]18∶2n−6. In hepatocytes incubated with [4,5-3H]-22∶6n−3, 20∶5n−3 was the main product. This retrocon-version was increased by EFA deficiency, as was peroxisomal β-oxidation
activity. This study shows that 18∶2n−6 and 18∶3n−3 can be elongated and desaturated in Atlantic salmon liver, and that this
conversion and the activity of retroconversion of very long chain PUFA is markedly enhanced by FFA deficiency. 相似文献
11.
The esterification, desaturation, and elongation of [1-14C]18∶3n−3, [1-14C]18∶2n−6, and [1-14C]20∶5n−3 at 5 and at 12°C were studied using cultivated hepatocytes from Atlantic salmon. The salmon were fed diets, in which
0, 50, or 100% of the supplementary fish oil had been replaced by soybean oil, for 950 day-degrees at 5 and 12°C. The endogenous
percentage of 18∶2n−6 in hepatocyte lipids was 2% in cells from fish fed a diet with 100% of the supplemental lipid from fish
oil, and it was slightly less than 25% in cells from fish fed the diet with 100% of the supplemental lipid from soybean oil.
Furthermore, the percentages of 20∶3n−6 and 20∶4n−6 were significantly higher in hepatocytes from fish fed on soybean oil
than they were in those of fish fed on fish oil. The percentages of 20∶5n−3 and 22∶6n−3, on the other hand, were lower. The
endogenous levels of n−6 FA were not significantly correlated with the total amounts of radiolabeled FA esterified in hepatocyte
lipids. The main radiolabeled products formed from 18∶2n−6 were 20∶2n−6 and 20∶3n−6. The level of the important eicosanoid
precursor 20∶4n−6 was twice as high in hepatocyte phospholipids from fish fed the 100% soybean oil diet as it was in hepatocytes
from fish fed the diet with 100% of supplemental lipid from fish oil. The main products formed from 18∶3n−3 were 20∶4n−3,
20∶5n−3, and 22∶6n−3. High levels of dietary 18∶2n−6 do allow, or even seem to increase, the production of 22∶6n−3 from 18∶3n−3
in hepatocytes. The main products formed from 20∶5n−3 were 22∶5n−3 and 22∶6n−3. The production of 22∶6n−3 from 20∶5n−3 was
higher at 5°C than at 12°C. The percentage of 24∶5n−3 was higher at 5°C than it was at 12°C, as was the ratio of 24∶5 to 22∶5.
These results suggest that the elongation rate of 22∶5n−3 to 24∶5n−3 is higher at the lower temperature. 相似文献
12.
Atlantic salmon were fed fish meal-based diets supplemented with either 100% fish oil (FO) or 100% rapeseed oil (RO) from
an initial weight of 85 g to a final average weight of 280 g. The effects of these diets on the capacity of Atlantic salmon
hepatocytes to elogate, desaturate, and esterify [1-14C]18∶1n−9 and the immediate substrates for the Δ5 desaturase, [1-14C]20∶3 n−6 and [1-14C]20∶4n−3, were investigated. Radiolabeled 18∶1n−9 was mainly esterified into cellular TAG, whereas the more polyunsaturated
FA, [1-14C]20∶3n−6 and [1-14C]20∶4n−3, were primarily esterified into cellular PL. More of the elongation product, [1-14C]20∶1n−9, was produced from 18∶1n−9 and more of the desaturation and elongation products, 22∶5n−6 and 22∶6n−3, were produced
from [1-14C]20∶3n−6 and [1-14C]20∶4n−3, respectively, in RO hepatocytes than in FO hepatocytes. Further, we studied whether increased addition of [1-14C]18∶1n−9 to the hepatocyte culture media would affect the capacity of hepatocytes to oxidize 18∶1n−9 to acid-soluble products
and CO2. An increase in exogenous concentration of 18∶1n−9 from 7 to 100 μM resulted in a nearly twofold increase in the amount of
18∶1n−9 that was oxidized. The conversion of 20∶4n−3 and 20∶3n−6 to the longer-chain 22∶6n−3 and 22∶5n−6 was enhanced by RO
feeding in Atlantic salmon hepatocytes. The increased capacity of RO hepatocytes to produce 22∶6n−3 was, however, not enought
to achieve the levels found in FO hepatocytes. Our data further showed that there were no differences in the hepatocyte FA
oxidation capacity and the lipid deposition of carcass and liver between the two groups. 相似文献
13.
The influence of age and cholesterol on polyunsaturated fatty acids (PUFa) levels was studied in young and old male Sprague-Dawley
rats. Animals were fed a fat-free diet supplemented with 10% (by wt) safflower oil with or without 1% cholesterol for 8 wk.
As a result of cholesterol feeding, proportions of linoleic acid (18∶2n−6) and dihomo-γ-linolenic acid (30∶3n−6) were increased
and and that of arachidonic acid (20∶4n−6) was decreased in the liver and platelet phospholipids in 64-wk-old rats, suggesting
inhibitory effects of cholesterol on 20∶4n−6 synthesis from 18∶2n−6. The prominent age-dependent effect on the levels of PUFA
was a retention of C−22 n−3 PUFA, accompanied by decreased C−22 n−6 PUFA and increased 20∶3n−6 in the liver and platelet phospholipids.
Ratio of 20∶3n−6/20∶4n−6 increased in 64-wk-old rats regardless of dietary cholesterol, suggesting depressed Δ5-desaturase
with age. In aorta phospholipids, 20∶3n−6 content and 20∶3n−6/20∶4n−6 ratio increased with cholesterol supplementation, but
not with age. These results suggest that changes of PUFA composition of platelet phospholipids with age are closely linked
with changes in liver phospholipids. The 20∶4n−6 content in both platelet and aorta phospholipids is kept constant, despite
other n−6 and n−3 PUFA being affected by age. 相似文献
14.
14C1-Linolenic acid was incorporated into lipids of hearts, livers, and carcasses of male rats. We studied the influence of diet
composition on extent and distribution of radioactivity. A CHOW diet, a purified, essential fatty acid (EFA)-deficient diet,
a purified control diet, and EFA-deficient diets with four fatty acid supplements were used. Supplements of 18∶2n−6, 20∶4n−6,
18∶3n−3, and 22∶6n−3 were given as single doses. Radioactivities in liver phosphatidyl ethanolamines (PE), phosphatidyl cholines,
and neutral lipids were measured. The distribution of radioactivity among the fatty acids in liver phospholipids was determined.
Rats on CHOW diet incorporated far less radioactivity than any other group into lipids of hearts and livers. Most of the activity
in livers was recovered as 20∶5n−3 and 22∶6n−3 in all rats. In EFA-deficient rats, the radioactivity in 22∶6n−3 of liver PE
was still increasing 36 hr after14C1-linolenic acid had been administered. The n−6 supplements (18∶2n−6 and 20∶4n−6) seemed to reduce the conversion of 20∶4n−3
to 20∶5n−3 (desaturation), whereas the n−3 supplements (18∶3n−3 and 22∶6n−3) reduced the conversion of 20∶5n−3 to 22∶5n−3
(elongation). Formation of 22∶6n−3 may be controlled by 22∶6n−3 itself at the elongation of 20∶5n−3 to 22∶5n−3. 相似文献
15.
The incorporation of [1-14C]linoleic acid, and [1-14C]linoleic acid into cellular lipids of cultured human skin fibroblasts was studied. Cultured cells took up both labeled fatty
acids at nearly the same rate and incorporated them into a variety of lipid classes. At the end of 1 hr incubation with [1-14C]linoleic acid, radioactivity was found in the triacylglycerol (TG) and choline phosphoglyceride (CPG) pools preferentially.
Incorporation into the TG fraction decreased rapidly, while the uptake into CPG, serine phosphoglyceride (SPG), and ethanolamine
phosphoglyceride (EPG) fractions increased progressively with longer incubation times. Similar results were obtained with
[1-14C]linoleic acid as precursor. At the end of 24 hr, desaturation and chain elongation of 18∶3 n−3 was more extensive than conversion
of 18∶2 n−6 to higher polyenoic acids. During pulse-chase experiments with either fatty acid precursor, the incorporated radioactivity
was progressively lost from cellular lipids, particularly from the TG and CPG fractions, but continued to increase in the
SPG and EPG pools. The similar labeling pattern of cellular phospholipids with linoleic or linolenic acids, and data from
pulse-chase studies suggest that a direct transfer of fatty acids from CPG to EPG is a likely pathway in fibroblast cultures.
Incorporation into the EPG pool during the pulse-chase experiments paralleled extensive desaturation and elongation of linoleic
acid into 20∶4 n−6, and 22∶4 n−6; and of linolenic acid into 22∶5 n−3 and 22∶6 n−3. 相似文献
16.
The purpose of this study was to examine the influence of long-term feeding of dietary fat rich in either n−3 or n−6 fatty
acids on the availability of arachidonic acid (20∶4n−6) in major phospholipids of gastric mucosa in rats. Three groups of
male Wistar rats were fed either a standard diet, a cod liver oil-enriched diet (10% by weight), or a corn oil-enriched diet
(10% by weight) for 8 mon. Dietary cod liver oil significantly reduced the level of 20∶4n−6 in phosphatidylcholine (PC) and
in phosphatidylethanolamine (PE) of gastric mucosa. The loss of 20∶4n−6 was compensated for by eicosapentaenoic acid (20∶5n−3)
in PC, whereas the decrease in 20∶4n−6 in PE corresponded to the increase in three n−3 fatty acids: 20∶5n−3, docosapentaenoic
acid (22∶5n−3), and docosahexaenoic acid (22∶6n−3). The level of 20∶5n−3 was higher than the level of 22∶6n−3 both in PC and
PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil increased the level of 18∶2n−6 but decreased the
monoene fatty acids 16∶1 and 18∶1n−7 in PC but not in PE of gastric mucosa. The 20∶4n−6 levels of both PC and PE were markedly
reduced by dietary cod liver oil, to about one-third of control levels. Similar changes were also observed in the stomach
wall. Gastric erosions were observed in all rats exposed to restriction stress, but this form of stress induced twice the
number of erosions in rats fed fish oil compared to control rats or rats fed corn oil. We conclude that a diet rich in fish
oil altered the balance between n−6 and n−3 fatty acids in major gastric mucosal phospholipids, markedly reduced the availability
of 20∶4n−6, and increased the incidence of gastric erosions induced by restriction or emotional stress. 相似文献
17.
The objective of this study was to determine the effect of 2,2-diphenyl-5-(4-{[(1E)-pyridin-3-yl-methylidene]-amino}piperazin-1-yl)pentanenitrile (SC-26196), a Δ6-desaturase inhibitor, on PUFA metabolism in human cells. SC-26196 inhibited the desaturation of 2 μM [1-14C] 18∶2n−6 by 87–95% in cultured human skin fibroblasts, coronary artery smooth muscle cells, and astrocytes. By contrast,
SC-26196 did not affect the conversion of [1-14C]20∶3n−6 to 20∶4 in the fibroblasts, demonstrating that it is selective for Δ6-desaturase. The IC50 values for inhibition of the desaturation of 2 μM [1-14C] 18∶3n−3 and [3-14C]24∶5n−3 in the fibroblasts, 0.2–0.4 μM, were similar to those for the inhibition of [1-14C] 18∶2n−6 desaturation, and the rates of recovery of [1-14C] 18∶2n−6 and [3-14C] 24∶5n−3 desaturation after removal of SC-26196 from the culture medium also were similar. SC-26196 reduced the conversion
of [3-14C] 22∶5n−3 and [3-14C] 24∶5n−3 to DHA by 75 and 84%, respectively, but it had no effect on the retroconversion of [3-14C] 24∶6n−3 to DHA. These results demonstrate that SC-26196 effectively inhibits the desaturation of 18- and 24-carbon PUFA
and, therefore, decreases the synthesis of arachidonic acid, EPA, and DHA in human cells. Furthermore, they provide additional
evidence that the conversion of 22∶5n−3 to DHA involves Δ6-desaturation. 相似文献
18.
When rats were fed a diet containing chow or fish oil for six weeks, the platelet phospholipid content and percent distribution
were similar. In the fish oil fed animals there was a 54, 40, 41, and 24% reduction, respectively, in the levels of 20∶4(n−6)
in the choline-, ethanolamine-, inositol-and serine-containing glycerophospholipids. Dietary fish oil increased the total
(n−3) polyunsaturated fatty acid content in all lipids. This effect was most pronounced in the ethanolamine glycerophospholipids
which now contained 26, 11, and 4 nmols of 20∶5(n−3), 22∶5(n−3), and 22∶6(n−3) in 109 cells. Ionophore A23187 stimulation of platelets from the chow fed rats resulted in the synthesis of 7, 64, and 3.5 nmols
of 12-hydroxy-5,8,10-heptadecatrienoic acid, 12-hydroxy-5,8,10,14-eicosatetraenoic acid and 12-hydroxy-5,8,10,14,17-eicosapentaenoic
acid, respectively, from 1×109 cells. The values from animals fed fish oil were 4, 18, and 27 nmol/109 platelets. It was not possible to detect any lipoxygenase products from 22∶5(n−3) or 22∶6(n−3), even though both acids are
readily metabolized by lipoxygenase when added directly to platelets. These findings suggest that 22-carbon (n−3) fatty acids
are not liberated when phospholipases are activated by calcium mobilization. 相似文献
19.
The fate of labeled linoleic, α-linolenic, and higher homologs of α-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 clam 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 administration of the acid, no radioactivity
was found in arachidonic, 20∶5 (n−3), or 22∶6 (n−3). Feeding the clams a culture ofPhaeodactylum tricornutum previously incubated with 1-14C-α-linolenic acid demonstrated that all the homologs of the α-linolenic series were found in the clam without any important
changes. Six hour administration of labeled linolenic acid resulted in the incorporation of the acid into diglycerides and
phospholipids.
Member of the carrera del Investigador Cientifico of the Consejo Nacional de Investigaciones Cientificas y Tecnicas 相似文献
20.
The effect of very low levels of dietary long-chain n−3 fatty acids on Δ6 desaturation of linoleic acid (18∶2n−6) and α-linolenic
acid (18∶3n−3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20∶3n−6), in liver microsomes and its influence on tissue
fatty acids were examined in obese and lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet containing
ca. 200 mg of long-chain polyunsaturated n−3 fatty acids per 100 g of diet were compared to those fed the same amount of α-linoleic
acid. Low amounts of long-chain n−3 fatty acids greatly inhibited Δ6 desaturation of 18∶2n−6 and Δ5 desaturation of 20∶3n−6,
while Δ6 desaturation of 18∶3n−3 was not inhibited in Zucker rats and was even stimulated in Wistar rats. Inhibition of the
biosynthesis of long-chain n−6 fatty acids was reflected in a decrease in arachidonic acid (20∶4n−6) content of serum lipids
when fasting, and also in the phospholipid fatty acids of liver microsomes. On the contrary, heart and kidney phospholipids
did not develop any decrease in 20∶4n−6 during fish oil ingestion. Docosahexaenoic acid (22∶6n−3), present in the dietary
fish oil, was increased in serum lipids and in liver microsome, heart, and kidney phospholipids. 相似文献