Showing papers on "Acyltransferase published in 1997"
TL;DR: The yeast sn-2 acyltransferase has been shown to encode a protein that can exhibit lysophosphatidic acid acyl transferase activity and that can be used to change total fatty acid content and composition as well as to alter the stereospecific acyl distribution of fatty acids in seed TAGs.
Abstract: A putative yeast sn-2 acyltransferase gene (SLC1-1), reportedly a variant acyltransferase that suppresses a genetic defect in sphingolipid long-chain base biosynthesis, has been expressed in a yeast SLC deletion strain. The SLC1-1 gene product was shown in vitro to encode an sn-2 acyltransferase capable of acylating sn-1 oleoyl-lysophosphatidic acid, using a range of acyl-CoA thioesters, including 18:1-, 22:1-, and 24:0-CoAs. The SLC1-1 gene was introduced into Arabidopsis and a high erucic acid-containing Brassica napus cv Hero under the control of a constitutive (tandem cauliflower mosaic virus 35S) promoter. The resulting transgenic plants showed substantial increases of 8 to 48% in seed oil content (expressed on the basis of seed dry weight) and increases in both overall proportions and amounts of very-long-chain fatty acids in seed triacylglycerols (TAGs). Furthermore, the proportion of very-long-chain fatty acids found at the sn-2 position of TAGs was increased, and homogenates prepared from developing seeds of transformed plants exhibited elevated lysophosphatidic acid acyltransferase (EC 2.3.1.51) activity. Thus, the yeast sn-2 acyltransferase has been shown to encode a protein that can exhibit lysophosphatidic acid acyltransferase activity and that can be used to change total fatty acid content and composition as well as to alter the stereospecific acyl distribution of fatty acids in seed TAGs.
342 citations
TL;DR: The CoA-independent transacylase is assumed to be involved in the accumulation of polyunsaturated fatty acids in ether- containing phospholipids and in the removal of deleterious ether-containing lysophospholipsids.
Abstract: Over 100 different phospholipid molecular species are known to be present in mammalian cells and tissues. Fatty acid remodeling systems for phospholipids including acyl-CoA: lysophospholipid acyltransferases, CoA-dependent and CoA-independent transacylation systems and lysophospholipase/transacylase are involved in the biosynthesis of these molecular species. Acyl-CoA:1-acyl-2-lysophospholipid acyltransferase prefers polyunsaturated fatty acyl-CoAs as acyl donors while acyl-CoA:2-acyl-1-lysophospholipid acyltransferase prefers saturated fatty acyl-CoAs. Therefore, the acyl-CoA:lysophospholipid acyltransferase system is involved in the synthesis of the phospholipid molecular species containing sn-1 saturated and sn-2 unsaturated fatty acids. The CoA-dependent transacylation system catalyzes the transfer of fatty acids esterified in phospholipids to lysophospholipids in the presence of CoA without the generation of free fatty acids. The CoA-dependent transacylation reaction in rat liver exhibits strict fatty acid specificity, i.e., three types of fatty acids (20:4, 18:2, and 18:0) are transferred. On the other hand, the CoA-independent transacylase catalyzes the transfer of C20 and C22 polyunsaturated fatty acids from diacyl phospholipids to various lysophospholipids, in particular, ether-containing lysophospholipids, in the absence of any cofactors. The CoA-independent transacylase is assumed to be involved in the accumulation of polyunsaturated fatty acids in ether-containing phospholipids and in the removal of deleterious ether-containing lysophospholipids. These acyltransferases and transacylases are involved in not only the remodeling of fatty acids but also the synthesis and degradation of some bioactive lipids and their precursors. In this review, the properties of these fatty acid remodeling systems and their possible roles in the biosynthesis of bioactive lipids are described.
301 citations
TL;DR: It is demonstrated that the regulated expression of the mitochondrial GPAT gene requires both NF-Y and ADD1/SREBPs, which regulates not only genes involved in cholesterol homeostasis and fatty acid synthesis but also a key enzyme in glycerolipid synthesis.
239 citations
TL;DR: Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mehanism leading to increased atherosclerosis in the presence of high plasma HDL levels.
Abstract: A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels.
227 citations
TL;DR: Data indicate that, when fatty acid is not limiting, triacsin blocks the acylation of glycerol 3-phosphate and diacylglycerol, but not the reacylation of lysophospholipids, which is interpreted to mean that acyl-CoAs must be selectively channelled towards specific acyltransferase reactions.
Abstract: The trafficking of acyl-CoAs within cells is poorly understood. In order to determine whether newly synthesized acyl-CoAs are equally available for the synthesis of all glycerolipids and cholesterol esters, we incubated human fibroblasts with [14C]oleate, [3H]arachidonate or [3H]glycerol in the presence or absence of triacsin C, a fungal metabolite that is a competitive inhibitor of acyl-CoA synthetase. Triacsin C inhibited de novo synthesis from glycerol of triacylglycerol, diacylglycerol and cholesterol esters by more than 93%, and the synthesis of phospholipid by 83%. However, the incorporation of oleate or arachidonate into phospholipids appeared to be relatively unimpaired when triacsin was present. Diacylglycerol acyltransferase and lysophosphatidylcholine acyltransferase had similar dependences on palmitoyl-CoA in both liver and fibroblasts; thus it did not appear that acyl-CoAs, when present at low concentrations, would be preferentially used to acylate lysophospholipids. We interpret these data to mean that, when fatty acid is not limiting, triacsin blocks the acylation of glycerol 3-phosphate and diacylglycerol, but not the reacylation of lysophospholipids. Two explanations are possible: (1) different acyl-CoA synthetases exist that vary in their sensitivity to triacsin; (2) an independent mechanism channels acyl-CoA towards phospholipid synthesis when little acyl-CoA is available. In either case, the acyl-CoAs available to acylate cholesterol, glycerol 3-phosphate, lysophosphatidic acid and diacylglycerol and those acyl-CoAs that are used by lysophospholipid acyltransferases and by ceramide N-acyltransferase must reside in two non-mixing acyl-CoA pools or, when acyl-CoAs are limiting, they must be selectively channelled towards specific acyltransferase reactions.
150 citations
TL;DR: Overexpression of these two cDNAs in mammalian cells leads to increased LPAAT activity in cell-free extracts using an in vitro assay that measures the conversion of fluorescently labeled LPA to PA, suggesting LPAat overexpression may amplify cellular signaling responses from cytokines.
Abstract: Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acetyltransferase (EC 2.3.1.51), catalyzes the conversion of LPA to PA. In this study, we describe the isolation and characterization of two human cDNAs that encode proteins possessing LPAAT activities. These two proteins, designated here as LPAAT-α and LPAAT-β, contain extensive sequence sequence similarities to microbial or plant LPAAT sequences. LPAAT-α mRNA was detected in all tissues with highest expression in skeletal muscle whereas LPAAT-β was expressed predominantly in heart and liver tissues. Expression of these two cDNAs in an Escherichia coli strain with a mutated LPAAT gene (plsC) complements its growth defect and shifts the equilibrium of cellular lipid content from LPA to PA and other lipids. Overexpression of these two cDNAs in mammalian cells leads to increased LPAAT activit...
143 citations
TL;DR: Genetic engineering of the unsaturation of fatty acids has been achieved by manipulation of the cDNA for the GPAT found in chloroplasts and has allowed modification of the ability of tobacco to tolerate chilling temperatures.
122 citations
TL;DR: A novel function for LCAT is demonstrated in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.
117 citations
TL;DR: It is concluded that C. neoformans produces highly active extracellular PLB, LPL, and LPTA under native conditions.
Abstract: We recently identified phospholipase activity as a potential virulence factor of Cryptococcus neoformans. We have now defined the nature of the phospholipase activity produced by a clinical isolate of C. neoformans var. neoformans, under native conditions, by 1H and 31P nuclear magnetic resonance (NMR) spectroscopy and thin-layer chromatography (TLC) of radiolabelled substrates. Glycerophosphocholine was identified by NMR spectroscopy as the sole phospholipid degradation product of the reaction between substrate phosphatidylcholine (PC) and cryptococcal culture supernatants indicating the presence of phospholipase B (PLB). No lysophosphatidylcholine (lyso-PC) or products indicative of phospholipase C, phospholipase D, or other lipase activity were identified. Use of PC and lyso-PC containing radiolabelled acyl chains and separation of products by TLC confirmed the PLB and lysophospholipase (LPL) activities. Lysophospholipase transacylase (LPTA) activity was identified by the formation of radioactive PC from lyso-PC. Extracellular enzyme production was maximal after 6 to 10 h in fresh medium. Assay conditions were optimized for pH, linearity with time, enzyme concentration, and saturation by substrates to allow comparison with phospholipases from other organisms. LPL activity was 10- to 20-fold greater than PLB activity, with mean (+/- standard deviation) specific activities of 34.9 +/- 7.9 and 3.18 +/- 0.2 micromol of substrate hydrolyzed per min per mg of protein, respectively. The response of PLB to increasing substrate concentrations was bimodal, whereas inhibition of LPL and LPTA activities occurred at concentrations of substrate lyso-PC greater than 200 microM. Enzyme activities were stable at acid pH (3.8), with pH optima of 3.5 to 4.5. Activities were unchanged in the presence of exogenous serine protease inhibitors, divalent cations, and EDTA. We conclude that C. neoformans produces highly active extracellular PLB, LPL, and LPTA under native conditions.
109 citations
TL;DR: Mitochondrial GPAT is upregulated at the transcriptional level by refeeding a high carbohydrate, fat-free diet to previously fasted mice and by insulin administration to diabetic animals, whereas microsomal GPAT activity is largely unaffected by these treatments.
80 citations
TL;DR: It is demonstrated that thelpxA gene from Neisseria meningitidis encodes a similar acyltransferase that selectively utilizes 3-hydroxylauroyl-ACP, a critical determinant of the length of the ester-linked hydroxyacyl chains found on lipid A in living cells.
TL;DR: Cl cloning of murine cDNA encoding 1-AGP acyltransferase (1- AGPAT), which converts LPA into phosphatidic acid by incorporating acyl moiety at an-2 position is reported.
Journal Article•
TL;DR: In this article, the structural and mechanistic features of 2-oxo acid dehydrogenase complexes are discussed, with special emphasis on the structure and role of the lipoyl domains in the complex.
Abstract: 2-Oxo acid dehydrogenase complexes are composed of multiple copies of at least three different enzymes, 2-oxo acid dehydrogenase, dihydrolipoyl acyltransferase and dihydrolipoamide dehydrogenase. The acyltransferase component harbours all properties required for multienzyme catalysis: it forms a large multimeric core, it contains binding sites for the peripheral components, the acyltransferase active site and mobile substrate carrying lipoyl domains that couple the active sites. In the past years these complexes have disclosed many of their secrets, providing currently a wealth of information on macromolecular structure, assembly and symmetry, active-site coupling, conformational mobility, substrate specificity and metabolic regulation. In this review we will discuss developments concerning the structural and mechanistic features of the 2-oxo acid dehydrogenase complexes, with special emphasis on the structure and role of the lipoyl domains in the complex.
TL;DR: The purification of a protein-palmitoyl acyltransferase (PAT) from human erythrocytes is described and PAT behaved as a peripheral membrane protein and catalyzed the attachment of palmitate in thioester linkage to the β-subunit of spectrin.
TL;DR: The biosynthetic pathway of gentiodelphin, a diacylated anthocyanin accumulating in G. triflora petals, is proposed on the basis of results, which caused a bathochromic shift and increased pigment stability in neutral to weakly basic pH.
Abstract: Acylation with hydroxycinnamic acids stabilizes anthocyanins and makes their colour bluer (bathochromic shift). We purified to homogeneity one acylation enzyme, hydroxycinnamoyl-CoA:anthocyanidin 3,5-diglucoside 5-O-glucoside-6′″-O-hydroxycinnamoyltransferase, from blue petals of Gentiana triflora. It is a single polypeptide protein of 52 kDa with a pi of 4.6. It catalyzes the transfer of the p-coumaric acid and caffeic acid from their CoA esters to the 5-glucosyl moiety of anthocyanidin 3,5-diglucosides but could not use malonyl-CoA as an acyl donor. Neither anthocyanidin 3-monoglucoside nor anthocyanins aromatically acylated at the 3-glucosyl moiety could be acylated by this enzyme. Aromatic acylation of anthocyanidin 3,5-diglucoside by this enzyme caused a bathochromic shift and increased pigment stability in neutral to weakly basic pH. Other anthocyanins from the petals of G. triflora were isolated and their structures were determined by fast-atom-bombardment MS and NMR. The biosynthetic pathway of genti-odelphin, a diacylated anthocyanin accumulating in G. triflora petals, is proposed on the basis of these results.
TL;DR: Results indicate that Arg-606 plays an important role in the binding of malonyl moieties to the transacylase domain but is not required for binding of acetyl moieties; these results are consistent with a mechanism whereby interaction between the positively charged guanidinium group ofArg-606 and the free carboxylate anion of the malonyL moiety serves to position this substrate in the active site of the enzyme.
TL;DR: The purified DGAT depended on exogenous sn-1,2-diolein and oleoyl-CoA, with the highest activity at about 200 and 20 microM, respectively, while sphingosine dose-dependently inhibited DGAT activity activated by PA and basal activity without PA.
Abstract: Diacylglycerol acyltransferase (DGAT) [EC 2.3.1.20] was purified to apparent homogeneity from the lipid body fraction of an oleaginous fungus, Mortierella ramanniana var. angulispora. The enzyme was solubilized from the lipid body fraction with 0.1% Triton X-100, and purified by subsequent column chromatography on Yellow 86 agarose, Superdex-200, Heparin-Sepharose, second Superdex-200, and second Yellow 86 agarose. The enzyme activity was finally enriched 4,802-fold over that of the starting 1,500X g supernatant. The apparent molecular mass of the enzyme was 53 kDa on SDS polyacrylamide gel electrophoresis. The purified enzyme did not exhibit glycerol-3-phosphate acyltransferase, lysophosphatidic acid acyltransferase, lipase, transacylase, or acyl-CoA hydrolase activities, although 2-monoolein was acylated with about a half of the enzyme activity toward 1,2-diolein. The purified DGAT depended on exogenous sn-1,2-diolein and oleoyl-CoA, with the highest activity at about 200 and 20 microM, respectively. Purified DGAT utilized a broad range of molecular species of both diacylglycerol and acyl-CoA as substrates. The highest activity was observed with sn-1,2-diolein and lauroyl-CoA. Anionic phospholipids such as phosphatidic acid (PA) activated the purified enzyme, as found for the Triton X-100 extract. Sphingosine dose-dependently inhibited DGAT activity activated by PA and basal activity without PA. These results provide a basis for further studies on the molecular mechanism of triacylglycerol biosynthesis and lipid body formation, in which DGAT plays an important role.
TL;DR: Analysis of cellular distribution of enzymes that esterify retinol and hydrolyze retinyl esters in liver of vitamin A-sufficient, -deficient, and deficient rats treated with retinoic acid or N-(4-hydroxyphenyl)-retinamide shows that LRAT and REH are differentially regulated by retinoids and that these enzymes also differ in their spacial distribution between liver parenchymal and nonparenchyl cells.
Abstract: The cellular distribution of enzymes that esterify retinol and hydrolyze retinyl esters (RE) was studied in liver of vitamin A-sufficient, -deficient, and deficient rats treated with retinoic acid or N-(4-hydroxyphenyl)-retinamide. Livers were perfused and cell fractions enriched in hepatocytes, and nonparenchymal cells were obtained for assays of RE and enzyme activity. The specific activity of lecithin:retinol acyltransferase (LRAT) was approximately 10-fold greater in the nonparenchymal cell than the hepatocyte fraction from both vitamin A-sufficient and retinoid-treated rats. Total RE mass, newly synthesized [3H]RE and LRAT activity were positively correlated in liver and isolated cells of both normal (P < 0.0001) and retinoid-treated rats (P < 0.0002). In nonparenchymal cells, these three constituents were nearly equally enriched as evaluated by their relative specific activity values (RSA, defined as the percentage of recovered activity divided by the percentage of recovered protein), which were each significantly greater than 1.0, with values of 4.3 for total RE mass (P < 0.05), 3.6 for newly synthesized [3H]RE (P < 0.01) and 3.8 for LRAT activity (P < 0.01). In contrast, the specific activities of neutral and acid bile salt-independent retinyl ester hydrolases (REH) did not vary with vitamin A status, and their RSA values were close to 1.0 in both hepatocytes and nonparenchymal cells. These data show that LRAT and REH are differentially regulated by retinoids and that these enzymes also differ in their spacial distribution between liver parenchymal and nonparenchymal cells.
TL;DR: This cDNA represents the first described sequence of a mammalian gene homologous to non-mammalian lysophosphatidic acid acyltransferases and suggests regulation of the enzyme by alternative splicing.
Abstract: A novel human homologue of Escherichia coli, yeast and plant 1-acylglycerol-3-phosphate acyltransferase has been isolated from U937 cell cDNA. Expression of the cloned sequence in 1-acylglycerol-3-phosphate acyltransferase-deficient E. coli resulted in increased incorporation of oleic acid into cellular phospholipids. Membranes made from COS7 cells transfected with the cDNA exhibited higher acyltransferase activity towards a range of donor fatty acyl-CoAs and lysophosphatidic acid. Northern-blot analysis of the cDNA sequence indicated high levels of expression in immune cells and epithelium. Rapid amplification of cDNA ends revealed differentially expressed splice variants, which suggests regulation of the enzyme by alternative splicing. This cDNA therefore represents the first described sequence of a mammalian gene homologous to non-mammalian lysophosphatidic acid acyltransferases.
TL;DR: This work confirmed the originality of the enzyme from Candida parapsilosis, which acts more like an acyltransferase than an hydrolase, which makes it an enzyme of choice for the direct bioconversion of oils in aqueous medium.
TL;DR: The results suggest that the DHAP-AT and G3P-AT activities are catalysed by two distinct enzymes associated with different sub-cellular compartments.
TL;DR: It is concluded that this region of 25 amino acids linked by a disulfide bond forms part of the interfacial binding domain of LCAT, which plays a role in interfacialbinding, while the active site core is not disrupted.
TL;DR: In this article the properties, assay, distribution, subcellular localization, deficiency in congenital peroxisomal disorders, purification and physiological functions of dihydroxyacetone phosphate acyltransferase (EC 2.3.1.42) are reviewed.
TL;DR: These features of the substrate specificity are exactly as predicted for a transferase that fulfills the proposed role in the fatty acid synthase reaction sequence and indicate that this activity plays an important role in determining the overall specificity of the beta-ketoacyl synthase Reaction.
Abstract: The enzyme activity responsible for translocation of saturated acyl chains from the 4‘-phosphopantetheine of the acyl carrier protein to the active site cysteine of the β-ketoacyl synthase in the animal fatty acid synthase has been identified. An enzyme assay was devised that allows uncoupling of the interthiol transfer step from the condensation reaction. Experiments with various fatty acid synthase mutants indicate clearly that catalysis of the transfer of saturated acyl moieties from the 4‘-phosphopantetheine thiol to the active site cysteine thiol, Cys-161, is an inherent property of the β-ketoacyl synthase domain. Catalytic efficiency of the interthiol transferase increases from C2 to C12 and decreases with increasing chain-lengths beyond C12. Malonyl, β-hydroxybutyryl, and crotonyl thioesters are not substrates for the transferase, whereas the β-ketobutyryl moiety is a poor substrate. These features of the substrate specificity are exactly as predicted for a transferase that fulfills the proposed ro...
TL;DR: This review attempts to capture the history of research involved in the understanding of lipid metabolism via investigation of the sn-glycerol-3-phosphate acyltransferase (glycerl-P acyl transferase), the first step in the synthesis of lipids in E. coli.
TL;DR: The hypothesis that the 154-171 segment of LCAT might be involved in the interaction of the enzyme with its lipid substrate is supported and the decreased activity of the Y156N natural LCAT mutant might result from a decreased affinity of this mutant for lipids.
Abstract: The 154–171 segment of the human lecithin-cholesterol acyltransferase (LCAT) enzyme was identified as the most stable amphipathic helix in the LCAT sequence. Its mean hydrophobicity, hydrophobic moment and its orientation at a lipid/water interface are similar to those of some of the helical repeats of apolipoprotein A-IV and E. This domain was therefore proposed as a candidate peptide accounting for the association between LCAT and its lipid substrate. To investigate this hypothesis we synthesized the LCAT-(154–171)-peptide, two variants containing the natural Y156N and R158C mutations and a variant with increased hydrophobicity through Y156I, L160I, L163I and Y171W substitutions. The structural and lipid-binding properties of these synthetic peptides were investigated by turbidity, fluorescence, electron microscopy and circular dichroism.
The wild-type peptide, the R158C variant in its dimeric form, as well as the more hydrophobic peptide, associated with phospholipids, whereas the Y156N and the R158C variant in its monomeric formdid not. However, only the complexes generated with the hydrophobic variant were stable enough to resist dissociation during gel filtration. The wild-type peptide and hydrophobic variant formed discoidal complexes with dimyristoylglycerophosphocholine (Myr2GraPCho) as shown by negative staining electron microscopy. Comparison of the properties of the wild-type and hydrophobic variant LCAT-(154–171)-peptide stresses the contribution of the hydrophobic face of the amphipathic helix to the formation and stabilization of the peptide/lipid complexes. This is further confirmed by the decreased affinity of the Y156N variant peptide for lipids, as this mutation decreased the mean hydrophobicity of the hydrophobic face of the amphipathic helix. These results support the hypothesis that the 154–171 segment of LCAT might be involved in the interaction of the enzyme with its lipid substrate and suggest that the decreased activity of the Y156N natural LCAT mutant might result from a decreased affinity of this mutant for lipids.
TL;DR: In this article, the authors postulate that the intrinsic acyl-CoA specificity of the acyltransferase, the flux of 1-acyl-GPC, 1-alkenyl-Gpc, as well as the pool size of acyl CoA are major factors in producing the final composition of the choline-containing phospholipids in the tissue.
TL;DR: It is shown that changing either of the cysteines to serine does not reduce enzymatic activity, indicating that the disulfide bond is not required for correct folding, and reduced extracellular levels of the mutant proteins are the result of their increased sensitivities to proteases encountered inside the cell during export.
Abstract: Vibrio and Aeromonas spp. secrete an unusual 35-kDa lipase that shares several properties with mammalian lecithin-cholesterol acyltransferase. The Aeromonas hydrophila lipase contains two cysteine residues that form an intramolecular disulfide bridge. Here we show that changing either of the cysteines to serine does not reduce enzymatic activity, indicating that the disulfide bond is not required for correct folding. However, when either of the cysteines is replaced, the enzyme is more readily denatured by urea and more sensitive to degradation by trypsin than is the wild-type enzyme, evidence that the bridge has an important role in stabilizing the protein's structure. The two mutant proteins with serine-for-cysteine replacements were secreted by Aeromonas salmonicida containing the cloned genes, although the levels of both in the culture supernatants were lower than the level of the wild-type enzyme. When the general secretory pathway was blocked with carbonyl cyanide chlorophenylhydrazone, the cell-associated pools of the mutant enzymes appeared to be degraded, whereas the wild-type pool remained stable. We conclude that reduced extracellular levels of the mutant proteins are the result of their increased sensitivities to proteases encountered inside the cell during export.
TL;DR: The results show that the increase in the FC/EC ratio in cancer patients is due to an impaired esterification of cholesterol by plasma LCAT, probably due to a alteration in the composition of substrate lipoproteins, or the presence of an inhibitory factor.
Abstract: An important factor which determines the movement of cholesterol in and out of the cells is the free cholesterol (FC)/esterified cholesterol (EC) ratio in the plasma. Although this ratio has been shown to be increased in several types of malignancies in humans as well as experimental animals, it is not known whether such an abnormality is found in breast cancer patients. Furthermore, the reasons for such an increase in cancer patients are unknown. We studied the plasma lipid composition and the activity of lecithin-cholesterol acyltransferase (LCAT), the enzyme responsible for the formation of most of EC in human plasma, in 12 women with breast cancer and 9 agematched control women. The plasma EC concentration was found to be significantly decreased in cancer patients, whereas the FC concentration was unchanged, leading to increased FC/EC ratios (P<0.05). The concentration of phosphatidylcholine, the acyl donor in the LCAT reaction, was decreased significantly, whereas all other phospholipids were unaffected. The cholesterol-esterifying activity of LCAT was significantly lower in cancer patients, whether assayed with endogenous substrates (P<0.05), or with an exogenous substrate (P<0.01). However, another function of the enzyme, namely the lysolecithin acyltransferase activity, was increased (P<0.02), indicating that the enzyme concentration in plasma may not be decreased. These results show that the increase in the FC/EC ratio in cancer patients is due to an impaired esterification of cholesterol by plasma LCAT, probably due to an alteration in the composition of substrate lipoproteins, or the presence of an inhibitory factor.
Patent•
18 Jun 1997TL;DR: In this paper, isolated gene encoding acyltransferase is provided which is functional to catalyze reaction to form sugar esters and a method for forming palmityl esters of glucose comprising reacting 1-O-palmitoyl-β-D-glucose with itself, with glucose or with palmity l partial ester of glucose in the presence of a catalytically effective amount of acyl transferase.
Abstract: Essentially pure acyltransferase is provided which is functional to catalyze reaction to form sugar esters. Also provided is isolated gene encoding acyltransferase. Additionally provided is a method for forming palmityl esters of glucose comprising reacting 1-O-palmitoyl-β-D-glucose with itself, with glucose or with palmityl partial ester of glucose in the presence of a catalytically effective amount of acyltransferase.