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PubMed2005

Biosynthetic pathway of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines.

The role of intercellular communication in the regulation of bacterial multicellular behavior has received widespread attention, and a variety of signal molecules involved in bacterial communication have been discovered. In addition to the N-acyl-homoserine lactones, 4-hydroxy-2-alkylquinolines (HAQs), including the Pseudomonas quinolone signal, have been shown to function as signal molecules in Pseudomonas aeruginosa. In this study we unraveled the biosynthetic pathway of HAQs using feeding experiments with isotope-labeled precursors and analysis of extracted HAQs by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Our results show that the biosynthesis of various HAQ metabolites is directed via a common metabolic pathway involving a "head-to-head" condensation of anthranilic acid and beta-keto fatty acids. Moreover, we provide evidence that the beta-keto-(do)decanoic acids, crucial for the biosynthesis of the heptyl and nonyl derivatives of the 4-hydroxyquinolines in P. aeruginosa, are at least in part derived from a common pool of beta-hydroxy(do)decanoic acids involved in rhamnolipid biosynthesis.

Chromatography, Gas↗
PubMed1993

Sebacic acid binding to human plasma albumin.

Sebacic (decanedioic) acid is a dicarboxylic acid proposed recently as an alternative energy substrate in total parenteral nutrition. In this paper, binding of sebacic acid to defatted human plasma albumin, also in the presence of decanoic acid, was studied by means of equilibrium dialysis. In addition, the binding of sebacic acid in human serum was investigated. Binding to defatted albumin was analysed by a model with two independent classes of sites with different affinity constants. The fitting procedure took into account some of the measurement errors that are likely to affect the equilibrium dialysis technique. We found for sebacic acid one binding site with affinity constant 3.69 x 10(4) M-1 and four to five sites with affinity constant 7.14 x 10(2) M-1. Association constants for decanoic acid are 3-4-fold larger than those of sebacic acid. Data of binding of sebacic acid in human serum suggested that only three to five of the low affinity sites are available for binding. When disodium sebacate is administered i.v. for total parenteral nutrition, a substantial fraction of sebacic anions is likely to be bound in serum.

Binding Sites↗
PubMed1992

Determination of the acyl moieties of the antibiotic complex A40926 and their relation with the membrane lipids of the producer strain.

Structures of the fatty acid residues characterizing the various components of A40926 were determined by gas chromatography/mass spectrometry on the methyl esters obtained by methanolysis of the complex. The results confirm the residues previously assigned to Factor A (n-undecanoic acid) and B (10-methyl-undecanoic acid) and establish the residues of Factor A1 (9-methyl-decanoic acid), B1 (n-dodecanoic acid), RS1 (8-methyl-nonanoic acid), RS2 (n-decanoic acid), and RS3 (n-tridecanoic acid). As the Actinomadura species contain in their mycelia large quantities of C15-C17 fatty acid residues as membrane phospholipids, these mycelia were saponified and the fatty acids obtained were analyzed as above. There is a close correlation between the fatty acid content of A40926 complex and that of the longer homologues in the producer mycelia.

Anti-Bacterial Agents↗
PubMed2005

Exploring the flexibility of ribosome recycling factor using molecular dynamics.

Ribosome recycling factor is proposed to be flexible, and that flexibility is believed to be important to its function. Here we use molecular dynamics to test the flexibility of Escherichia coli RRF (ecRRF) with and without decanoic acid bound to a hydrophobic pocket between domains 1 and 2, and Thermus thermophilus RRF (ttRRF) with and without a mutation in the hinge between domains 1 and 2. Our simulations show that the structure of ecRRF rapidly goes from having an interdomain angle of 124 degrees to an angle of 98 degrees independently of the presence of decanoic acid. The simulations also show that the presence or absence of decanoic acid leads to changes in ecRRF flexibility. Simulations of wild-type and mutant ttRRF (R32G) show that mutating Arg-32 to glycine decreases RRF flexibility. This was unexpected because the range of dihedral angles for arginine is limited relative to glycine. Furthermore, the interdomain angle of wild-type T. thermophilus goes from 81 degrees to 118 degrees whereas the R32G mutant remains very close to the crystallographic angle of 78 degrees . We propose that this difference accounts for the fact that mutant ttRRF complements an RRF deficient strain of E. coli whereas wild-type ttRRF does not. When the ensemble of RRF structures is modeled into the ribosomal crystal structure, a series of overlaps is found that corresponds with regions where conformational changes have been found in the cryoelectron microscopic structure of the RRF/ribosome complex, and in the crystal structure of a cocomplex of RRF with the 50S subunit. There are also overlaps with the P-site, suggesting that RRF flexibility plays a role in removing the deacylated P-site tRNA during termination of translation.

Binding Sites↗
PubMed2003

Degradation of alkanes and highly chlorinated benzenes, and production of biosurfactants, by a psychrophilic Rhodococcus sp. and genetic characterization of its chlorobenzene dioxygenase.

Rhodococcus sp. strain MS11 was isolated from a mixed culture. It displays a diverse range of metabolic capabilities. During growth on 1,2,4-trichlorobenzene, 1,2,4,5-tetrachlorobenzene (1,2,4,5-TeCB) and 3-chlorobenzoate stoichiometric amounts of chloride were released. It also utilized all three isomeric dichlorobenzenes and 1,2,3-trichlorobenzene as the sole carbon and energy source. Furthermore, the bacterium grew well on a great number of n-alkanes ranging from n-heptane to n-triacontane and on the branched alkane 2,6,10,14-tetramethylpentadecane (pristane) and slowly on n-hexane and n-pentatriacontane. It was able to grow at temperatures from 5 to 30 degrees C, with optimal growth at 20 degrees C, and could tolerate 6 % NaCl in mineral salts medium. Genes encoding the initial chlorobenzene dioxygenase were detected by using a primer pair that was designed against the alpha-subunit (TecA1) of the chlorobenzene dioxygenase of Ralstonia (formerly Burkholderia) sp. strain PS12. The amino acid sequence of the amplified part of the alpha-subunit of the chlorobenzene dioxygenase of Rhodococcus sp. strain MS11 showed >99 % identity to the alpha-subunit of the chlorobenzene dioxygenase from Ralstonia sp. strain PS12 and the parts of both alpha-subunits responsible for substrate specificity were identical. The subsequent enzymes dihydrodiol dehydrogenase and chlorocatechol 1,2-dioxygenase were induced in cells grown on 1,2,4,5-TeCB. During cultivation on medium-chain-length n-alkanes ranging from n-decane to n-heptadecane, including 1-hexadecene, and on the branched alkane pristane, strain MS11 produced biosurfactants lowering the surface tension of the cultures from 72 to </=29 mN m(-1). Glycolipids were extracted from the supernatant of a culture grown on n-hexadecane and characterized by (1)H- and (13)C-NMR-spectroscopy and mass spectrometry. The two major components consisted of alpha,alpha-trehalose esterified at C-2 or C-4 with a succinic acid and at C-2' with a decanoic acid. They differed from one another in that one 2,3,4,2'-trehalosetetraester, found in higher concentration, was esterified at C-2, C-3 or C-4 with one octanoic and one decanoic acid and the other one, of lower concentration, with two octanoic acids. The results demonstrate that Rhodococcus sp. strain MS11 may be well suited for bioremediation of soils and sediments contaminated for a long time with di-, tri- and tetrachlorobenzenes as well as alkanes.

Alkanes↗
PubMed1996

Effect of structurally diverse peroxisome proliferators on rat hepatic sulfotransferase.

Exposure to perfluorocarboxylic acids, pthalate esters, and some hypolipidemic agents results in the proliferation of peroxisomes in the rodent liver. The structural diversity of these compounds suggests mechanistic diversity in their toxicity as well. To establish reliable biomarkers of peroxisome proliferation (PP) in compounds with distinct chemical toxicities, this study investigated the effect of in vivo exposure to perfluoro-n-octanoic acid, perfluoro-n-decanoic acid, di(2-ethylhexyl)phthalate (DEHP) and clofibrate on two-dimensional electrophoretic protein patterns of rat hepatic sulfotransferases, ST1A1, ST1C1 and ST2A1. After exposure to peroxisome proliferative doses, both ST1A1 and ST1C1 abundance in whole liver homogenates was significantly reduced, but only as a result of perfluorocarboxylic and exposure. The well-established PPs, DEHP and clofibrate had no effect on sulfotransferase expression whatsoever. The observed down-regulation of these STs is significant with respect to their normal detoxication activities and its potential correlation to carcinogenesis warrants further study. The present investigation supports previous studies that demonstrate the unique features of perfluorocarboxylic acid toxicity, relative to classic peroxisome proliferators and endorses the continued use of 2D protein-mapping of Sts and other proteins as biomarkers of chemical toxicity.

Amino Acid Sequence↗
PubMed2006

Asymmetric total syntheses of marine cyclic depsipeptide halipeptins A-D.

Halipeptins A-D (1 a-d) are a family of natural cyclic depsipeptides isolated from marine sponges. Total syntheses of these four compounds are detailed in this report. The key elements in this synthesis include the elaboration of the polysubstituted decanoic acid parts by two asymmetric aldol reactions, assembly of the N-methyl-delta-hydroxyisoleucine residue by using either aza-Claisen rearrangement or methylation of aspartates as the key steps, and macrocyclization at the polysubstituted decanoic acid alanine site.

Alanine↗
PubMed1989

[Distribution and elimination of medium- and long-chain fatty acids of a fat emulsion in lipoproteins of severely injured patients following bolus injection].

A fat emulsion containing 20% fat as medium chain triglycerides (MCT) and long chain triglycerides (LCT) (1:1) was injected as a bolus in an amount of 0.2g fat per kg body weight to six patients, three to five days after a serious injury. Triglyceride concentrations increased within two min in lipoprotein fractions d less than 0.95 g/ml (Chylomicrons), d less than 1.006 g/ml (VLDL), d less than 1.063 g/ml (LDL) and d less than 1.21 g/ml (HDL). Sixty minutes after injection triglyceride concentrations had again reached preexperimental values in all lipoprotein fractions. Cholesterol values did not change. According to the composition of the fat emulsion, linoleic acid content increased in triglycerides of all lipoprotein fractions, whereas octanoic and decanoic acid did so only in triglyceride-rich lipoproteins (d less than 1.006). Half-life values of elimination of octanoic acid (3.3 min) and decanoic acid (3.9 min) in triglycerides of lipoprotein fraction d less than 1.006 were nearly half as short as that of long chain fatty acids (linoleic acid, 6.4 min; oleic acid, 6.5 min; palmitic acid, 7.5 min). Thus in contrast to LCT, MCT are only found in triglyceride-rich lipoproteins (d less than 1.006) and are also eliminated more rapidly.

Fat Emulsions, Intravenous↗
PubMed1991

Biological activities of melanotropic peptide fatty acid conjugates.

Four fatty acids (FA, palmitic, myristic, decanoic, hexanoic) were individually conjugated to the N-terminus of the alpha-MSH fragment analog, H-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10-NH2. This resulted in enhanced potency of the conjugates (compared to the unconjugated melanotropin analog) as determined in the lizard skin bioassay and in the mouse melanoma cell tyrosinase bioassay. The shorter conjugates of hexanoic and decanoic acid were at least equipotent to alpha-MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogs were 100 times less active. The myristoyl and palmitoyl conjugates exhibited a "creeping" potency in the lizard skin bioassay-that is, potency of the peptides increased with time in contact with the skins. These observations may be related to the more lipid nature of these FA-conjugates. In the tyrosinase assay, the conjugates were 10-100 times more active than alpha-MSH or the unconjugated analog. Each of the FA-melanotropic peptide conjugates exhibited prolonged (residual) melanotropic activity in both the lizard skin and melanoma cell bioassays. In other words, after removal of the melanotropin conjugates from contact with the skins or cells, responses were still manifested for hours or days thereafter. As little as 1 hr of contact with melanoma cells resulted in enhanced enzyme activity as measured 48 hr later. Since the conjugates, but not H-[Asp5, D-Phe7, Lys10]alpha-MSH5-10-NH2, exhibited prolonged activity, the conversion of reversible agonists to irreversible agonists was demonstrated.

Amino Acid Sequence↗
PubMed1987

[Heat-stable hemolysin of Pseudomonas aeruginosa].

Pseudomonas aeruginosa produces at least two distinct hemolysins: heat-labile hemolysin, which is known as phospholipase C, and heat-stable hemolysin, which is considered to be a glycolipid but its true nature is not found yet. Cellophane agar plate method was applied to hasten and enhance the hemolysin production by Pseudomonas aeruginosa, and the hemolysin obtained by this method was examined biochemically. This heat-stable hemolysin consisted of two major acidic glycolipids. One was considered to be the same glycolipid as that obtained by the same method of Jarvis and Johnson's from the peptone-glycerol culture filtrate of the same organism, which is composed of two moles of rhamnose and two moles of beta-hydroxy decanoic acid, and the other one being a glycolipid composed of one mole of rhamnose and two moles of beta-hydroxy decanoic acid. By this method, the rhamnolipid with one mole of rhamnose was produced more than the rhamnolipid with two moles of rhamnose, and they were produced in the same ratio from the first to fifth culture day. From the examinations of hemolytic activities of the hydrolyzed products of these glycolipids, the hemolysis producing moiety of the hemolysin was considered to be the dimer of beta-hydroxy decanoic acid contained in the glycolipid molecule. Hemolytic activities of these glycolipids are regarded as their detergent like effects. Since these activities are interfered by small amount of serum protein, their pathogenic role would not be important in vitro. However, their interaction with other toxic substances produced by this organism would be subject to be solved.

Bacteriological Techniques↗
PubMed1993

Diacylglycerol is an effector of the clonal expansion of cells containing activated Ha-ras genes.

Diacylglycerols (DAG) are lipid second messengers which are generated during phospholipase-catalyzed hydrolysis of phospholipids. The model DAG, sn-1,2-didecanoylglycerol (DIC10), is an effective topical tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. We now report that 11/12 of DMBA-initiated/DIC10-promoted papillomas examined contain an A-->T mutation in the 61st codon of the Ha-ras gene, suggesting that DAGs affect the clonal expansion of activated Ha-ras-containing cells. To explore further the DIC10-induced clonal expansion of activated Ha-ras-containing cells, we have examined the tumor-promoting effect of DIC10 in the skin of transgenic TG.AC mice, which harbor a v-Ha-ras transgene. By 9 weeks of promotion, 100% of the TG.AC mice developed squamous papillomas and by 15 weeks these mice developed > 20 papillomas/mouse. Because fatty acids are known to participate in signal transduction pathways, and since cellular lipases could cleave the fatty acid side chains present in DIC10, we have examined the tumor promoting activity of n-decanoic acid to verify the specificity of promotional activity of DIC10. n-Decanoic acid did not function as a tumor promoter. These data implicate DAG as an effector of the clonal expansion of mutated Ha-ras-containing cells, and support a mechanism whereby an increase in endogenous DAG could contribute to the clonal expansion of cells containing a Ha-ras oncogene.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Fatty acid and positional selectivities of gastric lipase from premature human infants: in vitro studies.

Gastric lipase activity in aspirates from premature human infants was tested for fatty acid and positional selectivity using racemic diacid triacylglycerols (TG) as substrates. The resulting free fatty acids and monoacylglycerols (MG) were recovered and analyzed. Octanoic acid (8:0) and decanoic acid (10:0) were hydrolyzed with a preference of 61.5:1 and 2.4:1 compared to palmitic acid (16:0) from rac-16:0-8:0-8:0 and rac-16:0-10:0-10:0, respectively. The ratio of lauric acid (12:0) to oleic acid (18:1) hydrolyzed from rac-18:1-12:0-12:0 was 13:1. Myristic acid (14:0), 18:1 and linoleic acid (18:2) were released at similar rates. These data and the composition of the MG suggest that, in vitro, the lipase is selective for shorter chain fatty acids and for fatty acids on the primary positions of the TG backbone.

Caprylates↗
PubMed1975

The inhibitory action of fatty acids on the growth of Escherichia coli.

The effect of fatty acids on Escherichia coli K12 was dependent on the source of the inoculum, the growth phase and the washing of the bacteria. The effects of saturated fatty acids from C4 to C16 and oleic acid at two concentrations (0-I and 0-4%, w/v) were determined on E. coli K12/154 growing exponentially in five different culture media. Depending on the media, 0-I % fatty acids increased the doubling times of the cultures by up to 96 %. Fatty acids of medium chain length (C6 to CII) at 0-4 % produced a decrease in cell concentration, nonanoic and decanoic acids being the most effective. A correlation was found between the decrease in cell concentration and the loss of viability of the culutres after addition of 0-4 % decanoic acid, with stationary-phase bacteria being affected more than those from exponential-phase cultures. Experiments carried out with E. coli B and C gave results similar to those obtained with E. coli K12/154.

Acetates↗
PubMed1991

Inhibition of long-chain acyl-CoA synthetase by the peroxisome proliferator perfluorodecanoic acid in rat hepatocytes.

Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator and is known to affect hepatic lipid metabolism in rats. The effects of PFDA on fatty acid utilization were examined in isolated rat hepatocyte suspensions and in rat liver mitochondria and microsomes. PFDA inhibited the oxidation of palmitic acid but not octanoic or pyruvic acids when hepatocytes were incubated with 1 mM PFDA. At this PFDA concentration the esterification of palmitic acid into triacylglycerols was also reduced. The activity of long-chain acyl-CoA synthetase (ACS), an enzyme essential for both oxidation and esterification of fatty acids, was reduced in hepatocytes incubated with 1 mM PFDA. Carnitine palmitoyltransferase (CPT), an important enzyme for the oxidation of long-chain fatty acids, was not altered in hepatocytes incubated with this PFDA concentration. In rat liver mitochondria, palmitate oxidation and ACS activity were reduced significantly (P less than 0.01) at a PFDA concentration that had no effect on CPT activity. The inhibition of ACS by PFDA was similar in liver mitochondria and microsome preparations. In mitochondria incubated with PFDA, the inhibition of ACS appears to be noncompetitive for the substrates palmitic acid and CoA. However, the ACS inhibition by PFDA appeared to be competitive for the ATP binding site of the enzyme. Several chain length perfluorinated fatty acids were examined for their ability to inhibit mitochondrial ACS. Short-chain perfluorinated fatty acids (perfluoroproprionic and -butyric acid) did not inhibit ACS activity. However, medium-chain perfluorinated acids (perfluorooctanoic, -ananoic and -decanoic acid) were found to be potent inhibitors of ACS in isolated mitochondria. Whether ACS inhibition is causally related to PFDA-induced peroxisome proliferation and altered lipid metabolism seen in vivo is yet to be determined.

Animals↗
PubMed1972

Fatty acid biosynthesis in rabbit mammary gland during pregnancy and early lactation.

The pattern of fatty acids synthesized by mammary-gland explants from rabbits during pregnancy and early lactation has been studied. From day 12 to day 18 of pregnancy, long-chain (C(14:0)-C(18:1)) fatty acids were the major products. From day 18 to day 21 of pregnancy there was an increase of up to 12-fold in the rate of fatty acid synthesis per unit wet weight of tissue that was almost exclusively caused by the synthesis of octanoic fatty acid and decanoic fatty acid, which are characteristic of rabbit milk. These medium-chain fatty acids were mainly incorporated into triglycerides. From day 22 to day 27 of pregnancy there was little change in the rate of fatty acid synthesis and the proportions of fatty acids synthesized were essentially the same as those synthesized by the lactating gland, i.e. 80-90% octanoic acid plus decanoic acid. About 2-4 days before parturition a second lipogenic stimulus occurred, although the pattern of fatty acids synthesized did not change.

Acetates↗
PubMed1995

Preparative-scale kinetic resolutions catalysed by microbial lipases immobilised in AOT-stabilised microemulsion-based organogels: cryoenzymology as a tool for improving enantioselectivity.

Gelatin-containing microemulsion based organogels have been used as an immobilisation matrix for lipases from a number of different sources. Kinetic resolutions of octan-3-ol, 1-octen-3-ol and 1-octyn-3-ol by esterification with decanoic acid have been performed using Chromobacterium viscosum (CV) lipase. CV lipase is highly enantioselective in favour of the (R)-(-) isomer of octan-3-ol, but the enantioselectivity is both reversed and decreased by the introduction of unsaturation at the 1-position. Marked improvements in enantioselectivity were achieved by carrying out the reaction at -15 degrees C, the enantiomeric excess of the ester product increasing from 47% (E = 3) to 73% (E = 8) in the case of 1-octen-3-ol, and from 17% (E = 1.4) to 38% (E = 2.5) in the case of 1-octyn-3-ol. The enantiomeric excess was approximately 85% (E approximately 15) for octan-3-ol, and there was no marked improvement in enantioselectivity even at -15 degrees C. Apparent activation energies for the esterification using decanoic acid of octan-3-ol, 1-octen-3-ol and 1-octyn-3-ol by CV lipase were 32 kJ mol-1, 31 kJ mol-1 and 41 kJ mol-1, respectively. This compares to an activation energy of 21 kJ mol-1 for the esterification of octan-1-ol with decanoic acid using CV lipase under the same conditions. Lipases from Pseudomonas (Fluka), Pseudomonas (Genzyme) and lipoprotein lipase ex Microbial (Genzyme) also selectively esterified the (R)-(-) isomer of racemic octan-3-ol, the two Pseudomonas preparations yielding product with an enantiomeric excess of 90%. Candida cylindracea lipase did not exhibit activity in gelatin-containing MBGs. Large-scale syntheses were performed in a 1 dm3 batch reactor in which 200 cm3 of pelleted MBG (containing 350 mg of CV lipase) was used repeatedly for the kinetic resolution of octan-3-ol.

Calorimetry↗
PubMed1996

The protein conformation of Cd-substituted horse liver alcohol dehydrogenase and its metal-site coordination geometry in binary and ternary inhibitor complexes.

The coordination geometry of the metal at the active site in Cd-substituted horse liver alcohol dehydrogenase (LADH) has been investigated for the binary complexes of LADH with imidazole, isobutyramide, decanoic acid and Cl-, and for the ternary complexes of LADH with NADH and imidazole, NADH and isobutyramide, NAD+ and decanoic acid and NAD+ and Cl-, by using the method of perturbed angular correlation of gamma-rays (PAC). The spectral results are consistent with a flexible structure around the metal for the binary complexes with inhibitors. For ternary complexes, however, a rigid structure is observed. An exception is the ternary complex between LADH, NADH and imidazole, in which the metal site is still flexible. Comparing with available structures determined by X-ray crystallography, we found a correlation between open structures and flexible metal sites, and between closed structures and rigid metal sites. This indicates that the PAC technique can be applied to distinguish the two conformations in solution. The spectral parameters, omega(o) and eta, of the experiments, except for the complexes with imidazole, fall into two groups: one with low omega(o) and one with high omega(o) (eta is relatively constant in all experiments). In this work it is clarified that the low omega(o) values are connected with the presence of a negatively charged solvent ligand. Using an angular-overlap approach to interpret the results, the low omega(o) values are found to be compatible with a coordination geometry where the S-Cd-S (Cys174 and Cys46 coordinate to the metal) angle is about 110 degrees as suggested in [Hemmingsen, L., Bauer, R., Danielsen, E., Bjerrum. M. J., Zeppezauer, M., Adolph, H. W., Formicka, G. & Cedergren-Zeppezauer, E. (1995) Biochemistry 34, 7145-7153], whereas high omega(o) values are compatible with an S-Cd-S angle of 130 degrees. The presence of a negatively charged metal ligand, therefore, might trigger the movement of the sulfur of Cys174. As it is believed that alcohols coordinate to the metal as alcoholate ions this could be important for catalysis.

Alcohol Dehydrogenase↗
PubMed1990

Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After incubation for 1 h the distribution of fluorescent fatty acids taken up by the lymphoid cell lines also differed with the chain length, most of the fluorescence being associated with phospholipid and triacylglycerols. In contrast with P10 and P12, P4 was not incorporated into neutral lipids. When the cells were incubated for 24 h with the pyrene fatty acids, the amount of fluorescent lipids synthesized by the cells was proportional to the fatty acid concentration in the culture medium. After a 24 h incubation in the presence of P10 or P12, at any concentration, the fluorescent triacylglycerol content of MLSM cells was 2-5-fold higher than that of control cells. Concentrations of pyrene fatty acids higher than 40 microM seemed to be more toxic for mutant cells than for control cells. This cytotoxicity was dependent on the fluorescent-fatty-acid chain length (P12 greater than P10 greater than P4). Pulse-chase experiments permitted one to demonstrate the defect in the degradation of endogenously biosynthesized triacylglycerols in MLSM cells (residual activity was around 10-25% of controls on the basis of half-lives and initial rates of P10- or P12-labelled-triacylglycerol catabolism); MLSM lymphoid cells exhibited a mild phenotypic expression of the lipid storage (less severe than that observed in fibroblasts). P4 was not utilized in the synthesis of triacylglycerols, and thus did not accumulate in MLSM cells: this suggests that natural short-chain fatty acids might induce a lesser lipid storage in this disease.

B-Lymphocytes↗