BBA - Molecular and Cell Biology of Lipids (v.1483, #1)
Stories about acyl chains by William E.M. Lands (1-14).
Molecular basis of exchangeable apolipoprotein function by Vasanthy Narayanaswami; Robert O Ryan (15-36).
Keywords: Exchangeable apolipoprotein; Apolipophorin III; Apolipoprotein E; Apolipoprotein A-I; Biophysical characterization; Spectroscopy; Lipid-free structure; Conformational flexibility;
Mobilisation of triacylglycerol stores by Geoffrey F Gibbons; Khwaja Islam; Richard J Pease (37-57).
Triacylglycerol (TAG) is an energy dense substance which is stored by several body tissues, principally adipose tissue and the liver. Utilisation of stored TAG as an energy source requires its mobilisation from these depots and transfer into the blood plasma. The means by which TAG is mobilised differs in adipose tissue and liver although the regulation of lipid metabolism in each of these organs is interdependent and synchronised in an integrated manner. This review deals principally with the mechanism of hepatic TAG mobilisation since this is a rapidly expanding area of research and may have important implications for the regulation of plasma very-low-density lipoprotein metabolism. TAG mobilisation plays an important role in fuel selection in non-hepatic tissues such as cardiac muscle and pancreatic islets and these aspects are also reviewed briefly. Finally, studies of certain rare inherited disorders of neutral lipid storage and mobilisation may provide useful information about the normal enzymology of TAG mobilisation in healthy tissues.
Keywords: Lipase; Liver; Adipose tissue; Very-low-density lipoprotein; Intracellular transport; Energy transfer;
A metabolic path for the degradation of lysophosphatidic acid, an inhibitor of lysophosphatidylcholine lysophospholipase, in neuronal nuclei of cerebral cortex by R.Roy Baker; Huu-yi Chang (58-68).
Neuronal nuclei isolated from rabbit cerebral cortex were found to be enriched in an NEM-insensitive lysophosphatidic acid (lysoPA) phosphohydrolase activity. LysoPA is an inhibitor of the nuclear lysophosphatidylcholine (lysoPC) lysophospholipase, and by preserving lysoPC levels, lysoPA boosted the nuclear production of the acyl analogue of platelet-activating factor by promoting the acetylation of lysoPC (Baker and Chang, Mol. Cell Biochem., 1999, in press). The nuclear phosphohydrolase converts lysoPA to 1-monoacylglycerol, and thus eliminates this lysoPA inhibition of lysoPC lysophospholipase. The nuclear lysoPA phosphohydrolase specific activity was more than three times that observed for the nuclear lysoPA lysophospholipase (Baker and Chang, Biochim. Biophys. Acta 1438 (1999) 253–263) and represents a more active route for nuclear lysoPA removal. The neuronal nuclear lysoPA phosphohydrolase was inhibited at acidic pH, and also inhibited by calcium ions. The 1-monoacylglycerol product of the phosphohydrolase is rapidly degraded by neuronal monoacylglycerol lipase, an enzyme some sevenfold more active than the phosphohydrolase and sensitive to inhibition by arachidonoyl trifluoromethyl ketone (AACOCF3). Both acidic pH and free fatty acid inhibited the lipase. In the absence of AACOCF3, production of fatty acid from lysoPA substrate could be largely attributed to the sequential actions of the nuclear phosphohydrolase and lipase. This facilitates fatty acid recycling back into phospholipid by lysophospholipid acylation when ATP levels are restored following periods of brain ischemia. At relatively low concentrations, sphingosine-1-phosphate, and alkylglycerophosphate were the most effective phosphohydrolase inhibitors while phosphatidic acid, alkylacetylglycerophosphate and ceramide were without effect. LysoPA is an interesting regulatory molecule that can potentially preserve lysophosphatidylcholine within the nuclear membrane for use in acetylation reactions. Thus conditions relevant to brain ischemia such as falling pH, falling ATP concentrations, rising fatty acid and intracellular calcium levels may, by slowing this metabolic path for lysoPA loss, promote the production of acyl PAF and contribute to the increased levels of the acetylated lipids noted in ischemia.
Keywords: Lysophosphatidic acid phosphohydrolase; Monoacylglycerol lipase; Lysophosphatidic acid; Regulation; Neuronal nucleus; Rabbit cerebral cortex;
Role of exogenous inositol and phosphatidylinositol in glycosylphosphatidylinositol anchor synthesis of GP49 by Giardia lamblia by Anna B Subramanian; Solangel Navarro; Rosa A Carrasco; Matthias Marti; Siddhartha Das (69-80).
Although Giardia lamblia trophozoites are unable to carry out de novo phospholipid synthesis, they can assemble complex glycophospholipids from simple lipids and fatty acids acquired from the host. Previously, we have reported that G. lamblia synthesizes GP49, an invariant surface antigen with a glycosylphosphatidylinositol (GPI) anchor. It is therefore possible that myo-inositol (Ins), phosphatidylinositol (PI) and other GPI precursors are obtained from the dietary products of the human small intestine, where the trophozoites colonize. In this report, we have investigated the role of exogenous Ins and PI on GPI anchor synthesis by G. lamblia. The results demonstrate that [3H]Ins and PI internalized by trophozoites, metabolically transformed into GlcN(acyl)-PI and downstream GPI molecules. Further investigations suggest that G. lamblia expresses cytidine monophosphate (CMP)-dependent (Mg2+-stimulated) and independent (Mn2+-stimulated) inositol headgroup exchange enzymes, which are responsible for exchanging free Ins with cellular PI. We observed that 3-deoxy-3-fluoro-D-myo-inositol (3-F-Ins) and 1-deoxy-1-F-scyllo-Ins (1-F-scyllo-Ins), which are considered potent inhibitors of Mn2+-stimulated headgroup exchange enzyme, inhibited the incorporation of [3H]Ins into PI and GPI molecules significantly, suggesting that CMP-independent (Mn2+-stimulated) exchange enzyme may be important for these reactions. However, 3-F-Ins and 1-F-scyllo-Ins were not effective in blocking the incorporation of exogenously supplied [3H]PI into GPI glycolipids. Thus, it can be concluded that G. lamblia can use exogenously supplied [3H]PI and [3H]Ins to synthesize GPI glycolipids of GP49; while PI is directly incorporated into GPI molecules, free Ins is first converted into PI by headgroup exchange enzymes, and this newly formed PI participates in GPI anchor synthesis.
Amyloid precursor protein in unique cholesterol-rich microdomains different from caveolae-like domains by Hideki Hayashi; Tetsuya Mizuno; Makoto Michikawa; Christian Haass; Katsuhiko Yanagisawa (81-90).
To determine the localization of the amyloid precursor protein (APP) on the cellular membrane, we performed membrane fractionation of cultured cells including that of Madin–Darby canine kidney (MDCK) and P19 cells transfected with human APP cDNA, non-transfected SH-SY5Y cells, and rat cerebral cortices. In MDCK cells, APP was exclusively present in abundance in the supernatant following solubilization of the plasma membranes using Triton X-100, and in high-density fractions of sucrose density gradient fractionation (SDGF) following Triton X-100 solubilization of whole cellular membranes. Caveolin-1 was not cofractionated with APP. In experiments using P19 cells and rat cerebral cortices, we detected two isoforms of APP. The APP with the apparently lower molecular weight (immature type) coexisted in abundance with integrin in the high-density fractions, whereas the APP with the apparently higher molecular weight (mature type) was recovered predominantly in the low-density fractions with cholesterol and GM1 gangliosides, the concentrations of which were higher than those in the bulk plasma membranes, but lower than those in caveolae-like domains (CLDs), following SDGF of Triton X-100-solubilized cellular membranes. The results of this study suggest the following; first, APP is not present in abundance in caveolae or CLDs, but is in unique cholesterol-rich microdomains; second, the targeting of APP to these unique microdomains may be linked to the maturation of APP in some cells.
Keywords: Amyloid precursor protein; Caveolae-like domain; Cholesterol; GM1 ganglioside; Amyloid β-protein; Detergent;
Mechanism of thiyl radical-catalyzed isomerization of unsaturated fatty acid residues in homogeneous solution and in liposomes by H. Sprinz; J. Schwinn; S. Naumov; O. Brede (91-100).
NMR spectroscopy and gas chromatography were used on methanolic solutions of fatty acid methyl esters and on small bilayer liposomes to study the radical-induced denaturation of the fatty acid residues from the natural cis-configuration into trans-isomers. To analyze the mechanism of the thiyl radical-catalyzed lipid isomerization, we compared the effects of thiols on oleic and linoleic fatty acid residues using pulse radiolysis, γ-radiolysis and chemolysis (AAPH) to generate thiyl radicals. The isomerization step takes place within the adduct of the thiyl radical to an olefinic group of unsaturated fatty acids, but not within the pentadienyl radical. The stability of the adduct can be described by an equilibrium constant of (12±5) mol−1 dm3. The isomerization rate depends on the structure of the thiol. However, the resulting isomeric equilibrium (trans-fraction: 81%) does not depend on the structure of the thiyl radical or the organization of the lipids. Quantum chemical calculations were performed to estimate the barriers for rotation, the geometry and the enthalpy difference between cis- and trans-thiyl radical adducts.
Keywords: Isomerization; Fatty acid; Thiol; γ-Irradiation; Pulse radiolysis; Liposome;
Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-β, fibronectin and renin by Makoto Miyazaki; Naoya Takemura; Shiro Watanabe; Noriaki Hata; Yoshihisa Misawa; Harumi Okuyama (101-110).
We have noted that n–3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by ∼10% as compared with linoleate (n–6)-rich safflower oil. Rapeseed oil with a relatively low n–6/n–3 ratio unusually shortened the survival time by ∼40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-β, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n–6/n–3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-β, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.
Keywords: Docosahexaenoic acid; Rapeseed oil; TGF-β; Renin; Fibronectin; Stroke-prone spontaneously hypertensive rat;
Induction of apoptosis by novel synthesized acylamides of human lymphocytes by Misa Ogura; Shizuo Handa (111-118).
To investigate a pathway to apoptosis which may involve ceramides and to elucidate the minimum structure which leads to apoptosis, we synthesized several novel acylamides. Although the four synthesized compounds were different in structure from C2-ceramide, they caused Jurkat cells to undergo apoptosis. The most effective of them was N-myristoyl-d-alaninol (d-MA), as shown by DNA fragmentation (detected with propidium iodide) and a decrease in the mitochondrial transmembrane potential (ΔΨm) (detected with rhodamine 123). Nevertheless, peripheral blood leukocytes exhibited no change after d-MA exposure, like after C2-ceramide or anti-Fas antibody treatment. The DNA fragmentation and ΔΨm caused by d-MA were blocked by a caspase-3 specific inhibitor as in the case of anti-Fas antibody stimulation. Quantification of ceramides by metabolic labeling with [14C]palmitic acid and HPTLC showed no increases in the ceramide levels on stimulation with d-MA, C2-ceramide or anti-Fas antibodies. Furthermore, d-MA had an apoptosis-inducing effect on an anti-Fas-resistant subline of Jurkat cells. These data suggest that d-MA may cause apoptosis of Jurkat cells without distinct ceramide formation and that this apoptotic pathway is very comparable, i.e. not identical, to that induced by anti-Fas antibodies.
Keywords: Lymphocyte; Ceramide; Apoptosis;
The pathway from arachidonic to docosapentaenoic acid (20:4n-6 to 22:5n-6) and from eicosapentaenoic to docosahexaenoic acid (20:5n-3 to 22:6n-3) studied in testicular cells from immature rats by Kjetil Retterstøl; Trine B. Haugen; Bjørn O. Christophersen (119-131).
The concentration-dependent metabolism of 1-14C-labelled precursors of 22:5n-6 and 22:6n-3 was compared in rat testis cells. The amounts of [14C]22- and 24-carbon metabolites were measured by HPLC. The conversion of [1-14C]20:5n-3 to [3-14C]22:6n-3 was more efficient than that of [1-14C]20:4n-6 to [3-14C]22:5n-6. At low substrate concentration (4 μM) it was 3.4 times more efficient, reduced to 2.3 times at high substrate concentration (40 μM). The conversion of [1-14C]22:5n-3 to [1-14C]22:6n-3 was 1.7 times more efficient than that of [1-14C]22:4n-6 to [1-14C]22:5n-6 using a low, but almost equally efficient using a high substrate concentration. When unlabelled 20:5n-3 was added to a cell suspension incubated with [1-14C]20:4n-6 or unlabelled 22:5n-3 to a cell suspension incubated with [1-14C]22:4n-6, the unlabelled n-3 fatty acids strongly inhibited the conversion of [1-14C]20:4n-6 or [1-14C]22:4n-6 to [14C]22:5n-6. In the reciprocal experiment, unlabelled 20:4n-6 and 22:4n-6 only weakly inhibited the conversion of [1-14C]20:5n-3 and [1-14C]22:5n-3 to [14C]22:6n-3. The results indicate that if both n-6 and n-3 fatty acids are present, the n-3 fatty acids are preferred over the n-6 fatty acids in the elongation from 20- to 22- and from 22- to 24-carbon atom fatty acids. In vivo the demand for 22-carbon fatty acids for spermatogenesis in the rat may exceed the supply of n-3 precursors and thus facilitate the formation of 22:5n-6 from the more abundant n-6 precursors.
Keywords: Docosahexaenoic acid; Docosapentaenoic acid; Essential fatty acid; Rat Sertoli cells; Testicular cells;
An active-site titration method for lipases by Didier Rotticci; Torbjörn Norin; Karl Hult; Mats Martinelle (132-140).
A method for active-site titration of lipases has been developed based on irreversible inhibition by methyl p-nitrophenyl n-hexylphosphonate. This method was applied to five lipases displaying from minor to pronounced interfacial activation. Soluble and immobilized lipases were successfully titrated in aqueous media. A low concentration of sodium dodecyl sulfate was needed for lipases displaying pronounced interfacial activation. The carrier of some of the immobilized preparations adsorbed part of the produced p-nitrophenolate. This problem could be solved by extracting the p-nitrophenolate after inhibition. The method was extended to apolar organic solvents in the case of immobilized lipase preparations.
Keywords: Concentration; Immobilized lipase; Aqueous medium; Organic medium; Interfacial activation; Detergent; Inhibitor;
Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats by Kaori Minehira; Shinichiro Inoue; Michiko Nonaka; Kyoichi Osada; Koji Yamada; Michihiro Sugano (141-153).
Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Δ6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4+/CD8+ T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in both ages. This alleviation may be associated with a large amount of lactoglobulin in WPI. These results thus showed a possibility that oxidized cholesterol-induced perturbations of age-related changes of lipid metabolism and immune function can be moderated by both the selection and combination of dietary protein.
Keywords: Dietary protein; Oxidized cholesterol; Lipid metabolism; Spleen; Immunoglobulin; Leukotriene B4; Rat;
Sphingosine 1-phosphate induces arachidonic acid mobilization in A549 human lung adenocarcinoma cells by Valeria Vasta; Elisabetta Meacci; Serena Catarzi; Chiara Donati; Marta Farnararo; Paola Bruni (154-160).
In the present paper, the effect of sphingosine 1-phosphate (Sph-1-P) on arachidonic acid mobilization in A549 human lung adenocarcinoma cells was investigated. Sph-1-P provoked a rapid and relevant release of arachidonic acid which was similar to that elicited by bradykinin, well-known pro-inflammatory agonist. The Sph-1-P-induced release of arachidonic acid involved Ca2+-independent phospholipase A2 (iPLA2) activity, as suggested by the dose-dependent inhibition exerted by the rather specific inhibitor bromoenol lactone. The Sph-1-P-induced release of arachidonic acid was pertussis toxin-sensitive, pointing at a receptor-mediated mechanism, which involves heterotrimeric Gi proteins. The action of Sph-1-P was totally dependent on protein kinase C (PKC) catalytic activity and seemed to involve agonist-stimulated phospholipase D (PLD) activity. This study represents the first evidence for Sph-1-P-induced release of arachidonic acid which occurs through a specific signaling pathway involving Gi protein-coupled receptor(s), PKC, PLD and iPLA2 activities.
Keywords: Sphingosine 1-phosphate; Bradykinin; Arachidonic acid; Protein kinase C; Phospholipase A2; Phospholipase D; A549 epithelial cell;
Phosphatidylinositol 3′-kinase-mediated calcium mobilization regulates chemotaxis in phosphatidic acid-stimulated human neutrophils by Rafat A. Siddiqui; Denis English (161-173).
Phosphatidylinositol 3′-kinase (PI 3′-kinase) plays an important role in the migration of hepatocytes, endothelial cells and neoplastic cells to agonists which activate cellular tyrosine kinases. We examined the PI 3′-kinase-dependent chemotactic responses of neutrophilic leukocytes induced by phosphatidic acid (PA) in order to clarify mechanisms by which the enzyme potentially influences cellular migration. Western analysis of immunoprecipitates indicated that PA induced the tyrosine phosphorylation of three distinct proteins involved in functional activation which co-immunoprecipitated in PA-stimulated cells. These proteins were identified as lyn, syk and the 85 kDa regulatory subunit of PI 3′-kinase. Chemotactic responses to PA but not to several other neutrophil agonists were inhibited by the PI 3′-kinase inhibitors wortmannin and LY294002. Chemotactic inhibition resulted from upstream inhibition of calcium mobilization. Chelation of extracellular calcium by ethylene glycol-bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid (EGTA) did not affect the PA-induced chemotaxis, whereas chelation of intracellular calcium by 1,2-bis(2-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA) attenuated this response. Thus, changes in intracellular Ca2+ levels that can be effected by Ca2+ mobilized from intracellular stores in the absence of Ca2+ influx regulate PA-induced chemotaxis. Furthermore, PI 3′-kinase inhibition blunted the agonist-dependent generation of inositol 1,4,5-trisphosphate (IP3), suggesting that PI 3′-kinase exerted its effects on calcium mobilization from intracellular sources by mediating activation of phospholipase C (PLC) in PA-stimulated cells. Moreover, the PI 3′-kinase inhibitor LY294002 also inhibited phosphorylation of syk in PA-stimulated cells. We, therefore, propose that products of PI 3′-kinase confined to the inner leaflet of the plasma membrane play a role in activation of syk, calcium mobilization and induction of chemotactic migration.
Keywords: Phosphatidic acid; Calcium mobilization; Phosphatidylinositol 3′-kinase; Actin polymerization; Protein tyrosine kinase; Chemotaxis; Neutrophil;
Fatty acids specifically related to the anisotropic properties of plasma membrane from rat urothelium by R.O. Calderón; A.R. Eynard (174-184).
Four different luminal surfaces of rat urothelium differing in their fatty acid composition were prepared by dietary induction. In order to induce lipid changes, each of four groups of rat received a basal diet rich in one of the unsaturated n-3, n-6 or n-9 fatty acid families and a commercial (control) diet. The effects of the dietary regime on the fatty acid composition of luminal urothelial membranes and their relation to the mobility of fluorescent probes were studied. In comparison with the control diet membrane, all three fatty acid-rich diets induced a decrease of the percentage amount of saturated fatty acid while that of the unsaturated fatty acids was increased. Accordingly, all three diets increased the unsaturation index in comparison with the control diet. The anisotropy across each membrane fraction was assessed using the n-(9-anthroyloxy) fatty acid fluorescent probes 3-AS, 7-AS and 12-AS, which locate at different depths in the membrane. Two different anisotropy profiles were observed. One profile showed the highest anisotropy at the C7 depth, whereas the other exhibited a continuous decrease of the anisotropy from the surface to the center of the bilayer. The molecular properties (isomerization) of 18:2n-9 fatty acid may account, at least in part, for the observed V-shaped profile (the ascending trend) of the membrane anisotropy values as a function of the respective 18:2n-9 fatty acid contents. Nevertheless, the minimum value of the profile did not correspond to the minimum 18:2n-9 fatty acid content, but rather to the higher amount of docosahexaenoic (22:6n-3) fatty acid. Thus, a modulating role of the 22:6n-3 fatty acid on the rigidifying effect of 18:2n-9 fatty acid is suggested, possibly mediated by relationships between fatty acid composition, saturated and unsaturated chain lengths, and freedom of motion of the phospholipid acyl chains.
Keywords: Urinary bladder; Transitional epithelium; Anisotropy; Dietary fatty acid; Unsaturation; Bilayer packing;
Microsomal fatty acyl-CoA transacylation and hydrolysis: fatty acyl-CoA species dependent modulation by liver fatty acyl-CoA binding proteins 1 1 This work was supported in part by a grant from the USPHS National Institutes of Health, DK41402. by Christopher A. Jolly; David C. Wilton; Friedhelm Schroeder (185-197).
Liver and intestinal cytosol contain abundant levels of long chain fatty acyl-CoA binding proteins such as liver fatty acid binding protein (L-FABP) and acyl-CoA binding protein (ACBP). However, the relative function and specificity of these proteins in microsomal utilization of long chain fatty acyl-CoAs (LCFA-CoAs) for sequential transacylation of glycerol-3-phosphate to form phosphatidic acid is not known. The results showed for the first time that L-FABP and ACBP both stimulated microsomal incorporation of the monounsaturated oleoyl-CoA and polyunsaturated arachidonoyl-CoA 8–10-fold and 2–3-fold, respectively. In contrast, these proteins inhibited microsomal utilization of the saturated palmitoyl-CoA by 69% and 62%, respectively. These similar effects of L-FABP and ACBP on microsomal phosphatidic acid biosynthesis were mediated primarily through the activity of glycerol-3-phosphate acyltransferase (GPAT), the rate limiting step, rather than by protecting the long chain acyl-CoAs from microsomal hydrolase activity. In fact, ACBP but not L-FABP protected long chain fatty acyl-CoAs from microsomal acyl-CoA hydrolase activity in the order: palmitoyl-CoA>oleoyl-CoA>arachidonoyl-CoA. In summary, the data established for the first time a role for both L-FABP and ACBP in microsomal phosphatidic acid biosynthesis. By preferentially stimulating microsomal transacylation of unsaturated long chain fatty acyl-CoAs while concomitantly exerting their differential protection from microsomal acyl-CoA hydrolase, L-FABP and ACBP can uniquely function in modulating the pattern of fatty acids esterified to phosphatidic acid, the de novo precursor of phospholipids and triacylglycerols. This may explain in part the simultaneous presence of these proteins in cell types involved in fatty acid absorption and lipoprotein secretion.
Keywords: Liver; Acyl-CoA; Binding protein; Microsome; Phosphatidic acid;