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Viruses take advantage of the host's protein modification and targeting pathways to modify their own proteins and to ensure that they assume active configurations and locate appropriately for assembly. In many viruses, one recurrent theme in such processes is exploitation of cellular protein acylation pathways for the addition of myristic and palmitic acid to capsid or envelope proteins.
The post-translational modifications of poliovirus proteins have been investigated by analysis of glycosylation, sulphation, phosphorylation and acylation of the proteins made in the infected HeLa cells. No glycosylation or sulphation of proteins specific for virus-infected cells was apparent. A number of changes in the pattern of phosphorylated proteins took place. The specific myristylation of the structural protein VP4 and its precursors was clearly apparent. Acylation of viral proteins with oleic or palmitic acid was not detected. Myristylation took place in the presence of the protease inhibitor ZnCl2, but not in the presence of inhibitors of translation, such as cycloneximide and anysomycin.
1. After the injection of sodium [1-(14)C]acetate, the highest incorporation of (14)C into the lipids of the silkworm was observed after 24hr. 2. The specific radioactivity of the palmitic acid fraction was greater and increased more rapidly than that of the stearic acid fraction, which was consistent with the precursor-product relationship to be expected on the basis of current concepts of fatty acid synthesis in vivo. 3. The results indicate the probability of synthesis of lipid components in tissues other than the fat body. 4. Fractionation studies indicate considerable differences in the rate of incorporation of [1-(14)C]acetate into neutral lipids and phospholipids between larvae and pupae as well as among tissues of larvae. 5. The rate of incorporation of [1-(14)C]acetate remains constant throughout pupal development.
The milk constituents of Dasyurus viverrinus, a carnivorous marsupial, exhibited major quantitative and qualitative changes during the course of lactation. The milk produced in the early stages of lactation was dilute, about 13-16% (w/w) solids before 3 weeks with carbohydrate representing the major fraction. In the latter stages of lactation the milk was concentrated, around 30% solids, and lipid was the predominant fraction. Palmitic acid was the major fatty acid present in early-stage milk but oleic acid became predominant in milk after 10 weeks post-partum. The changes in milk composition in D. viverrinus were similar to those described for the milks of herbivorous marsupials which therefore suggests that this pattern may be uniform throughout the Marsupialia.
More than 40 years ago, saturated FA with 12, 14, and 16 carbon atoms (lauric acid, myristic acid, and palmitic acid) were demonstrated to be "hypercholesterolemic saturated FA". It was further concluded that the serum total cholesterol level would hardly be changed by isocaloric replacement of stearic acid (18:0) by oleic acid (cis-18:1n-9) or carbohydrates. These earlier studies did not address the effects of the various FA on the serum lipoprotein profile. Later studies found that the hypercholesterolemic saturated FA increase serum total cholesterol levels by raising concentrations of both the atherogenic LDL and the antiatherogenic HDL. Consequently, the ratio of total to HDL cholesterol will hardly change when carbohydrates replace these saturated FA. Compared with other saturated FA, stearic acid lowers LDL cholesterol. Studies on the effects on HDL cholesterol are less conclusive. In some, the effects on HDL cholesterol were comparable to those of palmitic acid, oleic acid, and linoleic acid, whereas in others a decrease was observed. This may suggest that in this respect the source of stearic acid is of importance, which needs however further study. From all these studies, however, it can be concluded that stearic acid may decrease the ratio of total to HDL cholesterol slightly when compared with palmitic or myristic acid. Without doubt, the effects of stearic acid are more favorable than those of trans monounsaturated FA.
Fifteen healthy young women were fed diets enriched to 4% of energy with either palmitic acid (as palm oil) or lauric acid (as coconut oil). A randomized crossover study design was used so that subjects followed the two experimental diets for 4 wk, both preceded by consumption of a baseline diet for 2 wk. The experimental diets differed only with respect to the fatty acid composition: there was a substitution of 4% of energy intake with palmitic acid or lauric acid in the experimental diets for 4% of energy as monoenes in the baseline diet. There were no differences in the concentration of serum total or lipoprotein lipids, apolipoproteins A-I and B, and lipoprotein (a) or plasma cholesteryl ester transfer protein activity between the experimental diet periods. The VLDL cholesterol concentration (0.38 +/- 0.05 vs. 0.51 +/- 0.05 mmol/L, means +/- SEM, P = 0.01] and plasma cholesteryl ester transfer protein activity [78 +/- 5 vs. 88 +/- 6 mumol/(h.L), P = 0.007) were greater at the end of the lauric acid diet period than at the end of the preceding baseline diet period. No differences were found in glucose effectiveness, insulin sensitivity index or insulin secretion measured by the intravenous glucose tolerance test (Minimal Model method). In conclusion, in terms of serum lipids, lipoproteins, and glucose metabolism, palmitic acid was equal to lauric acid at 4% of total energy intake exchange, and both of these saturated fatty acids were comparable to a 4% of total energy intake exchange with monoenes in healthy young women.
Although liver fatty acid binding protein (L-FABP) is known to enhance uptake and esterification of straight-chain fatty acids such as palmitic acid and oleic acid, its effects on oxidation and further metabolism of branched-chain fatty acids such as phytanic acid are not completely understood. The present data demonstrate for the first time that expression of L-FABP enhanced initial rate and average maximal oxidation of [2,3-3H] phytanic acid 3.5- and 1.5-fold, respectively. This enhancement was not due to increased [2,3-3H] phytanic acid uptake, which was only slightly stimulated (20%) in L-FABP expressing cells after 30 min. Similarly, L-FABP also enhanced the average maximal oxidation of [9,10-3H] palmitic acid 2.2-fold after incubation for 30 min. However, the stimulation of L-FABP on palmitic acid oxidation nearly paralleled its 3.3-fold enhancement of uptake. To determine effects of metabolism on fatty acid uptake, a non-metabolizable fluorescent saturated fatty acid, BODIPY-C16, was examined by laser scanning confocal microscopy (LSCM). L-FABP expression enhanced uptake of BODIPY-C16 1.7-fold demonstrating that L-FABP enhanced saturated fatty acid uptake independent of metabolism. Finally, L-FABP expression did not significantly alter [2,3-3H] phytanic acid esterification, but increased [9,10-3H] palmitic acid esterification 4.5-fold, primarily into phospholipids (3.7-fold) and neutral lipids (9-fold). In summary, L-FABP expression enhanced branched-chain phytanic acid oxidation much more than either its uptake or esterification. These data demonstrate a potential role for L-FABP in the peroxisomal oxidation of branched-chain fatty acids in intact cells.
A new class of outer membrane lipid (OML) was isolated from the oral spirochete Treponema denticola strain ATCC 33521 using a phenol/chloroform/light petroleum procedure normally applied for lipopolysaccharide extraction. In addition to chemical analysis, Fourier transform infrared (FTIR) spectroscopy was applied to compare the biophysical properties of OML with lipopolysaccharides (LPS) and lipoteichoic acids (LTA). Isolated OML fractions represent 1.4% of the total dry cell weight, are about 4 kDa in size, and contain 6% amino sugars, 8% neutral sugars, 14% phosphate, 35% carbazol-positive compounds, and 11% fatty acids (containing iso- and anteiso-fatty acyl chains). Rare for outer membrane lipids, OML contains no significant amount of 3-deoxy-D-manno-octulosonic acids, heptoses, and beta-hydroxy fatty acids. The fatty acyl chain composition, being similar to that of the cytoplasmic membrane, is quite heterogeneous with anteiso-pentadecanoic acid (12%), palmitic acid (51%), and iso-palmitic acid (19%) as the predominant fatty acids present. Findings of a glycerol-hexose unit and two glycerol-hexadecanoic acid fragments indicate a glycolipid membrane anchor typically found in LTA. There was also no evidence for the presence of a sphingosine-based lipid structure. The results of FTIR measurements strongly suggest that the reconstituted lipid forms normal bilayer structures (vesicles) expressing a high membrane state of order with a distinct phase transition as typical for isolated LPS. However, in contrast to LPS, OML of T. denticola has a lower Tm near 22 degreesC and a lower cooperativity of the phase transition. The results suggest a different kind of permeation barrier that is built up by this particular OML of T. denticola, which is quite different from LPS normally essential for Gram-negative bacteria.
The initial rate of [1-14C]arachidonic acid (AA) entry in the serosal side of rabbit distal colonic mucosa mounted in Ussing-type chambers is linear and independent of intracellular metabolism. When the maximal AA uptake was plotted as a function of medium AA concentration in ranges between 50 and 500 nM, saturation of the AA uptake with increasing concentrations was observed. The time course of the uptake of oleic acid and palmitic acid was similar to that observed with AA, and their separate addition to incubation medium strongly reduced the AA uptake. The influx of arachidonate was largely inhibited by ouabain and by incubation with mucosal sodium-free solution and amiloride, while it was increased when colonic mucosa was exposed to luminal amphotericin B. However, voltage-clamp studies showed that the AA entry rate appeared to be linearly related (r = 0.99) to transepithelial potential difference (PD) and suggested that the sodium dependence of AA translocation is an indirect effect of the changes in transepithelial PD induced by sodium transport shifts. These features provide evidence that there is a common entry pathway for AA and other long-chain free fatty acids mediated by a mechanism of facilitated diffusion driven by transmembrane PD.
Fatty liver and kidney syndrome, a disorder of young chicks, was studied under laboratory conditions. Affected chicks had enlarged livers (hepatomegaly), an increased content of lipid in the liver, and an increased level of palmitoleic acid in the liver lipids. The disorder was observed mainly in chicks from young parent flocks, and was associated either with commerical diets which were subsequently found to be low in biotin, or with specially formulated low-biotin diets. A third factor, imposition of stress, was required to initiate the disorder. There was evidence of increased lipogenesis causing an increase of triacylglycerols in the liver lipids and an increased production of saturated fatty acids, particularly palmitic acid. Increased levels of palmitoleic acid resulted from an increased desaturation of palmitic acid. Under stress, affected chicks had low blood glucose levels, suggesting that gluconeogenesis was impaired. Since biotin-dependent enzymes are involved in both gluconeogenesis and lipogenesis, it would appear that the relevant enzymes respond differently to a deficiency of biotin.
BACKGROUND: Human milk contains palmitic acid predominantly in the triglyceride sn-2 position, and differs from the palmitic acid positional distribution found in most infant formulas (predominantly positions sn-1 and sn-3). Following lipolysis by pancreatic lipase, 2-monoglycerides and free fatty acids are produced. All 2-monoglycerides are well absorbed, including 2-monopalmitin, thus providing one reason for the efficient absorption of palmitic acid in breast-fed infants. If infants are fed fat blends with palmitic acid located in the sn-1 and sn-3 positions, the resulting free fatty acids may form poorly absorbed calcium soaps. Therefore, many infant formulas contain only modest levels of palmitic acid. METHODS: Fat absorption studies were conducted in rats with preparations containing various amounts of palmitic acid in the triglyceride sn-2 position. Determining total fat absorption, specific fatty acid absorption, and the presence of calcium-fatty acid soaps. RESULTS: Betapol, a new triacylglycerol, similar to human milk in its palmitic acid content and positional distribution, demonstrated excellent absorption characteristics compared to fat blends derived from either palm olein or oleo (similar in fatty acid profile to Betapol, but with most palmitic acid in the sn-1 and sn-3 positions). A five-point dose response was used to further evaluate the relationship of positional distribution and fat loss. Palmitic acid excretion and fecal fatty acid soaps were negatively correlated to the presence of palmitic acid in the sn-2 position. CONCLUSION: These studies provide evidence that palmitic acid can be efficiently absorbed, avoiding fatty soap formation of it is present in the sn-2 position.
Oxytocin(OT) is considered to have several activities besides strongly inducing myometrial contraction by activating phosphatidilinositol-specific phospholipase C(PI-PLC). These include reconstructing the phospholipid constituents of the cell membrane and activating a variety of fatty acid producing systems. On the other hand, pregnancy-related steroid hormones which are produced by the fetus, placenta and mother are considered to be closely involved in the maintenance of pregnancy and the initiation of labor. In the present study with cultured myometrial cells, we examined what effect these steroid hormones might exert on the intramyometrial production of fatty acid by OT. Our results confirmed bi-phasic production of arachidonic acid(AA), linoleic acid(LA), palmitic acid(PA), and stearic acid(SA) by OT. Phase 1 was an increasing but transient phenomenon having its peak at 30 sec. It is considered to be derived from phosphatidylinositol bis-phosphate. Phase 2 was a persistent and increasing phenomenon which was initiated after 120 sec. It is considered to be mediated by Ca-dependent phospholipase. We also studied the effect of steroid hormones on the production of fatty acid. For AA, LA, and PA, we confirmed that dehydroepiandrosterone sulfate(DHAS) shortened the time taken in reaching the peak of Phase 1 to half of that of the control, and progesterone(P) extended the time 2-3 fold. These findings suggest that DHAS, P and F might modify the human myometrial construction mechanism as a factor which regulates the quantity and velocity of fatty acid production.
Enzymatic pathways involved in the metabolism of lysophosphatidylcholine were investigated in rat heart myocardial cells. Acyl CoA-dependent acyltransferase activity was localized in microsomes, and was much greater than lysophospholipase activity in either cytosolic or microsomal fractions. The cytosolic lysophospholipase was more sensitive to inhibition by palmitylcarnitine in comparison to free fatty acids. In contrast, free fatty acids (oleate and palmitate) produced a greater inhibition of the microsomal acyltransferase and lysophospholipase than did palmitylcarnitine. A reduction in the assay pH to 6.5 resulted in an increase in microsomal acyltransferase and cytosolic lysophospholipase activities, but brought about a marked reduction in the microsomal lysophospholipase activity. At pH 6.5, the percentage inhibition of the microsomal acyltransferase by palmitylcarnitine was reduced, whereas the inhibition by palmitic acid was enhanced. The inhibition of the microsomal lysophospholipase by both palmitylcarnitine and palmitic acid was reduced at pH 6.5. With respect to myocardial ischemia, the inhibition of microsomal acyltransferase by free fatty acids and the reduction in microsomal lysophospholipase activity due to acidosis may contribute to the elevation of cellular lysophosphoglycerides which are arrhythmogenic.
We analyzed the colostrum of 11 mothers, consuming a normal hospital diet, for total fat content and various fatty acids. Three of the mothers had given birth four weeks prematurely. Total fat content of the colostrum ranged from 2.16 to 3.65 g/100 ml. The major fatty acids were palmitic acid (16:0) and oleic acid (18:1) (24.3 and 39.7% (w/w), respectively). The dominating polyunsaturated fatty acid was linoleic acid (18:2n-6) (11.5% of the total fatty acids). Linolenic acid (18:3n-3) and docosahexaenoic acid (22:6n-3) accounted for 0.7 and 0.6%, respectively, of the sum of total fatty acids. The ratio of polyunsaturated to saturated fatty acids was 0.42, ranging from 0.28 to 0.5, and the ratio of n-6/n-3 fatty acids was 6:1. Linoleic acid and linolenic acid were positively correlated with each other (p < 0.02), whereas palmitic acid was negatively correlated with oleic acid (p < 0.05). We conclude that the average human colostrum contains the recommended level and balance of the essential fatty acids required by the newborn baby.
The binding of [3H]oleic acid and [3H]palmitic acid to the low molecular weight fatty acid binding proteins present in the cytosols of rat liver and heart was studied. Both fatty acids were bound by Z protein of liver, whereas only oleic acid was bound by the fraction of heart that contains the fatty acid binding protein. However, after delipidation of heart cytosolic proteins with butanol, the binding of palmitic acid to the fatty acid binding protein was detected. In contrast to a published report (Gloster, J., and Harris, P. (1977) Biochem. Biophys. Res. Commun. 74, 506-513), oleic acid was not bound by rat heart or bovine heart myoglobin. Both rat heart fatty acid binding protein and rat liver Z protein were purified to homogeneity or near homogeneity. On polyacrylamide gel electrophoresis under nondenaturing conditions, liver Z protein gave rise to three bands, none of which was identical with the single band due to heart fatty acid binding protein. Rabbit antibodies to rat liver Z protein were used to demonstrate that the purified fatty acid binding protein from rat liver (Z protein) and rat heart are immunologically unrelated and that no Z protein is present in rat heart cytosol. Taken together, these observations lead to the conclusion that the low molecular weight fatty acid binding proteins from rat liver and heart are different proteins.
The large conductance Ca2+ activated K+ channel (BK channel) has been considered to play an important role in the excitability and contractility of vascular smooth muscle cells. Activation of the BK channel causes the hyperpolarization and relaxation of vascular smooth muscle cells. It has been reported that fatty acids can affect the BK channel activity and its concentration is increased significantly during myocardial ischemia. These reports suggest that fatty acids may contribute to the ischemic coronary vasodilation by increasing the BK channel activity. However, the underlying mechanism of fatty acid-induced activation of the BK channel is still uncertain. In the present study, we measured the effect of fatty acids on the BK channel activity in rabbit coronary smooth muscle cells by using patch clamp method and also examined its underlying mechanism. Arachidonic acid (AA) dissolved in DMSO activated the BK channel in a dose-dependent manner (from 0.5 to 10 microM), and DMSO (0.1%) alone had no effect on the activity of the BK channel. Arachidonic acid activated BK channels in both cell-attached and inside-out patches, but the onset and recovery of this effect were slower in the cell-attached patch configuration. The BK channel activity was also increased by other fatty acids, including myristic acid, linoleic acid, palmitoleic acid and palmitic acid. Long chain fatty acids were more effective than short chain fatty acids (myristic acid), and there was no statistical difference between the effect of saturated (palmitic acid) and unsaturated fatty acids (palmitoleic acid) on the BK channel activity. The concentration of Ca2+ and Mg2+ in the bathing solution had no appreciable effects on the AA-induced increase of BK channel activity. From the above results, it may be concluded that fatty acids directly increase the BK channel activity and may contribute to the ischemic coronary vasodilatation in rabbit coronary smooth muscle cells.
The metabolism of [14-14C]erucic acid and [U-14C]palmitic acid has been investigated in adipocytes isolated from rat epididymal fat. The rate of acylation of [14C]erucic acid in cellular lipids and oxidation to CO2 and acid-soluble activity was ca. 1/3 of the rate with [14C]palmitic acid as substrate. A maximal incorporation of fatty acids in triacylglycerol was found at a fatty acid concentration of 0.8 mM in the medium, both with [14C]erucic acid and [14C]palmitic acid as substrate. Glucose added to the medium increased the esterification and decreased the oxidation of both fatty acids. No significant chain-shortening of [14C]erucic acid to shorter monoenes was identified in the fat cells. Increasing concentrations of unlabeled palmitic acid in the incubation medium markedly inhibited the esterification of [14C]erucic acid, whereas unlabeled erucic acid had little effect on the rate of esterification of [14C]palmitic acid.
During short term incubations, radioactive arachidonic acid and palmitic acid were incorporated in the cholesteryl ester fraction of the lipids of cultured thyroid cells. Three times more arachidonic than palmitic acid was incorporated and the incorporation of both was dependent upon the culture conditions: the presence of 1 mU/ml thyrotropin in the culture medium during four days almost completely inhibited the subsequent incorporation of the two fatty acids in the cholesteryl ester fraction whereas the total cholesterol and cholesteryl ester content of the cells was not affected.