Biomedical subjects

Philippe Legrand

Publications and source records attributed to Philippe Legrand.

At least 19 recordsLinked to original sources

PubMed2006

Identification and characterization of recombinant and native rat myristoyl-CoA: protein N-myristoyltransferases.

Compared to other species that possess a single functional myristoyl-CoA: protein N-myristoyltransferase gene copy, human, mouse and cow possess 2 NMT genes, and more than 2 protein isoforms. In mammals, the contribution of each gene transcript to multiple protein isoform expression and enzyme activity remains unclear. In order to get new insight on their respective physiological role, we have cloned and characterized the two rat NMT cDNAs. Rat NMT1 and NMT2 cDNAs contain 1491 and 1590 nucleotides, respectively, with high identity with their mouse homologues. Polypeptide sequences exhibited 68.1% identity between NMT1 and 2. Recombinant rat NMT1 and 2 showed major immunoreactive forms at 66 and 50 kDa, although NMT2 is 33-amino acid longer than NMT1. Both proteins exhibited functional myristoyltransferase activity but NMT2 appeared to be 4-time less active than NMT1. Studies of native protein expression revealed that the level and sizes of NMT proteins greatly vary among rat tissues although NMT1 and 2 did not display tissue specific expression at the mRNA level. Altogether, these results suggest that NMT2 may contribute little to total NMT activity levels in vivo.

Acyl Coenzyme A↗

PubMed2006

Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity.

The importance of a high fat intake in the increasing prevalence of childhood and adult obesity remains controversial. Moreover, qualitative changes (i.e. the fatty acid composition of fats) have been largely disregarded. Herein is reviewed the role of polyunsaturated fatty acids (PUFAs) of the n-6 series in promoting adipogenesis in vitro and favouring adipose tissue development in rodents during the gestation/suckling period. Epidemiological data from infant studies as well as the assessment of the fatty acid composition of mature breast milk and infant formulas over the last decades in the Western industrialized world are revisited and appear consistent with animal data. Changes over decades in the intake of n-6 and n-3 PUFAs, with a striking increase in the linoleic acid/alpha-linolenic ratio, are observed. In adults, using a consumption model based upon production data, similar changes in the PUFA content of ingested lipids have been found for France, and are associated with an increase of fat consumption over the last 40 years. These profound quantitative and qualitative alterations can be traced in the food chain and shown to be due to changes in human dietary habits as well as in the feeding pattern of breeding stock. If prevention of obesity is a key issue for future generations, agricultural and food industry policies should be thoroughly reevaluated.

Adipogenesis↗

PubMed2005

Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and in vivo of anti-estrogens in human breast cancer and multiple myeloma.

Anticancer drug efficiency is governed by its bioavailability. In order to increase this parameter, we synthesized several injectable and biodegradable systems based on incorporation of anti-estrogens (AEs) in nanoparticles (NPs) and liposomes were synthesized. Both nanospheres (NS) and nanocapsules (NCs, polymers with an oily core in which AEs were solubilized) incorporated high amounts of 4-hydroxy-tamoxifen (4-HT) or RU 58668 (RU). Physico-chemical and biological parameters of these delivery systems, and coupling of polyethylene-glycol chains on the NP surface revealed to enhance the anti-tumoral activity of trapped AEs in a breast cancer MCF-7 cell xenograft model and to induce apoptosis. These features correlated with an augmentation of p21(Waf-1/Cip1) and of p27(Kip1) and a concomitant decrease of cyclin D1 and E in tumor extracts. Liposomes containing various ratios of lipids enhanced the apoptotic activity of RU in several multiple myeloma (MM) cell lines tested by flow cytometry. MM cell lines expressed both estrogen receptor alpha and beta subtypes except Karpas 620. Karpas 620 cells which did not respond to AEs became responsive following ER cDNA transfection. A new MM xenograft model was generated after s.c. injection of RPMI 8226 cells in nude mice. RU-loaded liposomes, administered i.v. in this model, at a dose of 12mgRU/kg/week, induced the arrest of tumor growth contrary to free RU or to empty liposomes. Thus, the drug delivery of anti-estrogens enhances their ability to arrest the growth of tumors which express estrogen receptors and are of particular interest for estrogen-dependent breast cancer treatment. In addition it represents a new potent therapeutic approach for multiple myeloma.

Apoptosis↗

PubMed2005

Humoral defence improvement and haematopoiesis stimulation in sows and offspring by oral supply of shark-liver oil to mothers during gestation and lactation.

Shark-liver oil (SLO) contains two bioactive lipids: alkylglycerols and n-3 PUFA. Alkylglycerols have immunostimulating and haematopoietic properties, while n-3 PUFA are essential for optimal neonatal development. We investigated the beneficial effects of dietary supplementation with 32 g SLO/d to twelve pregnant and then lactating sows (from day 80 of pregnancy to weaning) on the growth and immune status of their offspring, compared with a control group. Sows were vaccinated against Aujeszky's disease 21 d before term. Blood samples were collected from sows before treatment, on delivery and 14 d later, and from five piglets per litter on days 2, 21 and 36 after birth; colostrum and milk samples were collected 12 h, 14 and 28 d postpartum. Compared with controls, supplemented sows had higher levels of both erythrocytes and Hb in their blood, and higher concentrations of IgG, alkylglycerols and n-3 PUFA in their mammary secretions. In piglets from supplemented sows, leucocytes and IgG were higher. Supplementation with SLO resulted in an increase in Aujeszky antibodies in both blood and colostrum of sows after vaccination, together with an increase in Aujeszky antibodies in piglet blood. Our findings demonstrate that improvement of both passive and active immune status in piglets is related to the consumption of alkylglycerols associated with n-3 PUFA in the sow diet. The overall improvement in offspring health status by SLO supplementation to the mother could be of interest for optimisation of the lipid diet during and after pregnancy.

Administration, Oral↗

PubMed2005

Comparison of the efficacy and pharmacology of formulations of amphotericin B used in treatment of leishmaniasis.

PURPOSE OF REVIEW: Several lipid-based formulations of the antifungal and antiparasitic drug amphotericin B are now available on the market. The purpose of this review is to assess their efficacy against leishmaniasis in both experimental and clinical settings, and to point out new developments in the formulation of this antibiotic. RECENT FINDINGS: The development of resistance to pentavalent antimony compounds has shifted the emphasis to amphotericin B for the treatment of visceral leishmaniasis in India. Lipid formulations show good efficacy but are expensive. The treatment period with lipid formulations is shorter, however, which reduces hospitalization costs. As a result, in developed countries where these costs are an important proportion of the treatment, lipid formulations are preferred, whereas they remain largely inaccessible in developing countries. Lipid-associated amphotericin B has been found to be effective for secondary prophylaxis in HIV-positive patients, in studies carried out in European countries bordering the Mediterranean. SUMMARY: The reduced toxicity of lipid-based formulations of amphotericin B is no longer in doubt. In India, their efficacy against visceral leishmaniasis and shorter treatment periods compared with the conventional formulation with deoxycholate has to be counter-balanced against the very high cost. By contrast, in developed countries around the Mediterranean, where leishmaniasis occurs mainly in immunocompromised individuals, lipid formulations have become the treatment of choice for visceral disease. The efficacy against cutaneous lesions is variable, however, and in some reports oral miltefosine was active after failure of treatment with amphotericin B.

Amphotericin B↗

PubMed2004

New lipid formulation of amphotericin B: spectral and microscopic analysis.

UV-visible and dichroic spectrum analysis and electron microscopy have been used to characterize a new amphotericin B (AmB) lipid formulation prepared by a solvent displacement process. The composition was dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in molar ratio DMPC/DMPG/AmB 7:3:5, a similar composition to that of Abelcet. Although the latter has a "ribbon-like" structure, our process gave a thin disc-like structure. Analysis of circular dichroism (CD) and UV-visible spectra of formulations containing different percentages of AmB revealed that a minimum of AmB self-association was observed with 7:3:5 molar ratio. Varying the lipid ratio (DMPC/DMPG) while maintaining the fixed ratio of AmB yielded similar results when DMPC was in excess (DMPC/DMPG from 10:0 to 6:4). However, when the ratio was between 5:5 to 3:7, AmB self-aggregation increased. For compositions rich in DMPG (2:8 and 0:10), inversion of the CD spectrum was observed. The influence of the lipid composition on the morphology of the complex was also evident in electron microscopy. DMPC/DMPG/AmB (10:0:5) gave large unfracturable lamellae. The presence of DMPG shortened the lamellae, which often appeared as disc-like structures. AmB content, the presence of DMPG and the preparation process all contribute to generating these original structures with particular CD spectra.

Amphotericin B↗

PubMed2004

Dose effect of alpha-linolenic acid on PUFA conversion, bioavailability, and storage in the hamster.

If an increased consumption of alpha-linolenic acid (ALA) is to be promoted in parallel with that of n-3 long-chain-rich food, it is necessary to consider to what extent dietary ALA can be absorbed, transported, stored, and converted into long-chain derivatives. We investigated these processes in male hamsters, over a broad range of supply as linseed oil (0.37, 3.5, 6.9, and 14.6% energy). Linoleic acid (LA) was kept constant (8.5% energy), and the LA/ALA ratio was varied from 22.5 to 0.6. The apparent absorption of individual FA was very high (>96%), and that of ALA remained almost maximum even at the largest supply (99.5%). The capacity for ALA transport and storage had no limitation over the chosen range of dietary intake. Indeed, ALA intake was significantly correlated with ALA level not only in cholesteryl esters (from 0.3 to 9.7% of total FA) but also in plasma phospholipids and red blood cells (RBC), which makes blood components extremely reliable as biomarkers of ALA consumption. Similarly, ALA storage in adipose tissue increased from 0.85 to 14% of total FA and was highly correlated with ALA intake. As for bioconversion, dietary ALA failed to increase 22:6n-3, decreased 20:4n-6, and efficiently increased 20:5n-3 (EPA) in RBC and cardiomyocytes. EPA accumulation did not tend to plateau, in accordance with identical activities of delta5- and delta6-desaturases in all groups. Dietary supply of ALA was therefore a very efficient means of improving the 20:4n-6 to 20:5n-3 balance.

Adipose Tissue↗

PubMed2004

Pure antiestrogen RU 58668-loaded nanospheres: morphology, cell activity and toxicity studies.

Nanospheres (NS) formulated using biodegradable and biocompatible polymers, poly(D,L-lactide-co-glycolide) (PLGA), poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL), loaded with the pure anti-estrogen RU 58668 (RU), a promising estrogen-dependent anticancer agent, have been prepared. They all possess a small size compatible with an intratumoral extravasation behavior and their pegylation reduce significantly their zeta potential. Characterization by freeze fracture electron microscopy have shown that NS are spheric particles with a size ranging between 30 and 50nm and a tendency to agglomerate which is reduced by polyethylene glycol (PEG) grafting. PEG-grafted NS are all non-toxic as revealed by cell viability assay. A specific cellular model has been used to evaluate not only the release extent of the drug but also its biological activity. All formulations tested showed that they release slowly RU as measured by the delayed ability of RU to inhibit estrogen-induced transcription in human breast cancer cells and that they possess only a small amount of surface adsorbed RU.

Antineoplastic Agents, Hormonal↗

PubMed2004

Drug delivery systems for oestrogenic hormones and antagonists: the need for selective targeting in estradiol-dependent cancers.

The pleiotropic activity of oestrogens and their mechanism of action via their binding to the two oestrogen receptors alpha (ER alpha) and beta (ER beta) subtypes in the different tissues where oestrogens exert their action have been briefly described. The fate of these compounds trapped into different galenic forms is discussed with regard to their therapeutic applications. Firstly, the advantages and disadvantages of the different forms (pills, i.v. forms and transdermal patches) used in contraception are compared. Secondly, the therapeutic use of formulated oestrogens for the post-menopausal hormone replacement therapy (HRT) is analysed through the various results obtained in different trials. The link between HRT and the risks of breast cancer and cardiovascular disease is underlined. Finally, comparing the activity of selective oestrogen receptor modulators such as tamoxifen and pure anti-oestrogens such as RU58668 and ICI182780, we analysed the reasons leading to the need for a tumor targeting of the latters, but not of the former for the treatment of oestrogen-dependent breast cancer. Different injectable and biodegradable formulations, that lead to a remarkable anti-tumor efficiency in xenografts, have been recently developed and we believe that they may represent promising new administration ways of added therapeutic values for anti-oestrogens. Such devices could be extended to the delivery of other anti-cancer drugs with more aggressive activities than anti-oestrogens.

Antineoplastic Agents, Hormonal↗

PubMed2004

Oral intake of shark liver oil modifies lipid composition and improves motility and velocity of boar sperm.

The natural ether-lipids 1-O-alkylglycerols (alkyl-Gro) from shark liver oil improve boar sperm motility and fertility in vitro. We examined the effects of oral shark liver oil on motility and velocity parameters of sperm together with modifications of lipid composition. Eleven boars were used as control and 11 were fed with 40 g/day for 28 days and sperm was collected on Days 0, 14 and 28 in control and treated groups. After 28 days treatment, sperm motility was improved by 2.9% as well as velocity parameters (curvilinear velocity +10.75%, progressive velocity +18.8% and average path velocity +13.5%) and sperm lipid composition was modified as follows: alkyl-Gro with saturated chains were increased (C16:0 +40.1%, C18:0 +87.2%) while alkyl-Gro with unsaturated chains remained absent, as in the control group, despite the prominence of C18:1 and C16:1 in shark liver oil. The treatment also resulted in an overall increase in the proportion of n - 3 and n - 6 polyunsaturated fatty acids in sperm lipids with a prominent increase of docosahexaenoic acid over time (18.9 +/- 1.34% at Day 0 to 25.7 +/- 1.11% at Day 28) and compared to control (25.7 +/- 1.11% for treated versus 16.1 +6/- 0.81 % for control at Day 28, respectively). These data demonstrate the influence of lipid intake on boar sperm composition and functions and suggest that oral intake of shark liver oil might improve reproduction.

Animals↗

PubMed2004

Efficacy and pharmacokinetics of intravenous nanocapsule formulations of halofantrine in Plasmodium berghei-infected mice.

The efficacy and pharmacokinetics of a new parenteral formulation of halofantrine were studied in mice infected with Plasmodium berghei. The formulation consisted of nanocapsules with an oily core, prepared from either poly(D,L-lactide) (PLA) homopolymer or PLA that was surface modified with grafted polyethylene glycol chains. They were compared with a previously described intravenous halofantrine preparation. No toxic effects were observed with halofantrine in form of nanocapsules after intravenous administration for doses of up to 100 mg/kg, whereas the solubilized form in polyethylene glycol-dimethylacetamide was toxic at this dose. The halofantrine-loaded nanocapsules showed activity that was similar to or better than that of the solution in the 4-day test and as a single dose in severely infected mice, with only minimal differences between the two nanocapsule formulations. Halofantrine pharmacokinetics were determined in parallel with parasite development in severely infected mice. Nanocapsules increased the area under the curve for halofantrine in plasma more than sixfold compared with the solution throughout the experimental period of 70 h. Furthermore, nanocapsules induced a significantly faster control of parasite development than the solution in the first 48 h posttreatment. While the parasitemia fell more rapidly with PLA nanocapsules, the effect was more sustained with the surface-modified ones. This is consistent with surface-modified nanocapsules remaining longer in the circulation. These results suggest that nanocapsule formulations could provide a more favorable halofantrine profile in the plasma and reduce the intravenous dose necessary and therefore the toxicity, thus suggesting the use of halofantrine by a parenteral route in severe malaria.

Animals↗

PubMed2004

Natural alkylglycerols restrain growth and metastasis of grafted tumors in mice.

Alkylglycerols are natural etherlipids abundant in shark liver oil (SLO) in a diacylated form. SLO is known to have antitumor properties and was recently described as an inhibitor of tumor neovascularization. However, most studies did not discriminate between the respective activities of alkylglycerols and of fatty acids, which both have potent biological properties. In this work, a mouse model was used to investigate the antitumor effects of SLO and of alkylglycerols purified from the same source, both administered orally. We demonstrated that either pure alkylglycerols or SLO reduced the tumor growth in a similar manner, suggesting that alkylglycerols were involved in this effect. In alkylglycerol-treated mice, metastasis dissemination was reduced by 64 +/- 8%, whereas SLO effect was 30 +/- 9% below control. Purified alkylglycerols also decreased significantly plasmalogen content in tumors, whereas SLO had no such effect. Finally, we demonstrated that a 5-day treatment with alkylglycerols curtailed the presence in tumors of von Willebrand factor, a marker of endothelial cells. This result suggested an anti-angiogenic effect of alkylglycerols. In summary, alkylglycerols were shown to decrease the growth, vascularization, and dissemination of Lewis lung carcinoma tumors in mice. These findings suggest that the antitumor activity of SLO is likely mediated by the presence of alkylglycerols.

Angiogenesis Inhibitors↗

PubMed2003

Distinct roles of endoplasmic reticulum cytochrome b5 and fused cytochrome b5-like domain for rat Delta6-desaturase activity.

The Delta6-desaturase catalyzes key steps in long-chain polyunsaturated fatty acid biosynthesis. Although the gene coding for this enzyme has been isolated in diverse animal species, the protein structure remains poorly characterized. In this work, rat Delta6-desaturase expressed in COS-7 cells was shown to localize in the endoplasmic reticulum. As the enzyme contains an N-terminal cytochrome b5-like domain, we investigated by site-directed mutagenesis the role of this domain in the enzyme activity. The typical HPGG motif of the cytochrome b5-like domain, and particularly histidine in this motif, is required for the activity of the enzyme, whatever the substrate. Neither endogenous COS-7 cytochrome b5 nor coexpressed rat endoplasmic reticulum cytochrome b5 could rescue the activity of mutated forms of Delta6-desaturase. Moreover, when rat endoplasmic reticulum cytochrome b5 was coexpressed with wild-type desaturase, both proteins interacted and Delta6-desaturase activity was significantly increased. The identified interaction between these proteins is not dependent on the desaturase HPGG motif. These data suggest distinct and essential roles for both the desaturase cytochrome b5-like domain and free endoplasmic reticulum cytochrome b5 for Delta6-desaturase activity.

Animals↗

PubMed2003

In vitro and in vivo biologic evaluation of long-circulating biodegradable drug carriers loaded with the pure antiestrogen RU 58668.

We have developed a parenteral delivery system for the administration of the highly promising pure antiestrogen RU 58668 (RU). Two types of nanoparticles (NP) made of biodegradable copolymers and coated with polyethylene-glycol (PEG) chains were prepared: nanospheres (NS) (diameter, approximately 110 nm) and nanocapsules (NC) with an oily core (diameter, approximately 250 nm). The amount of RU incorporated into NS and NC was approximately 33 vs. approximately 5 microg RU/mg of polymer, respectively. Coating with PEG chains prolonged the antiestrogenic potency of RU, as shown by a prolonged antiuterotrophic activity of encapsulated RU into PEG-poly(D,L lactic acid) (PLA) NS, as compared to that of conventional nonpegylated NS. In mice bearing MCF-7 estrogen-dependent tumors, free RU injected at 4.3 mg/kg/week by i.v. route slightly decreased the estradiol-promoted (0.5 mg/kg/week) tumor growth while RU-loaded PEG-PLA NS injected at the same dose strongly reduced it. Analysis of cell cycle parameters in tumors treated with RU indicated that RU-loaded PEG-PLA NS injected at 4.3 mg/kg/week in MCF-7 tumors decreased cyclin D(1) and cyclin E simultaneously, and increased p27. The antitumoral activity of RU encapsulated within pegylated NC was stronger than that of RU entrapped with pegylated NS loaded at an equivalent dose. Indeed, the former decreased the tumor size in nude mice transplanted with the estrogen receptor-positive but estrogen-independent MCF-7/Ras breast cancer cells at a concentration 2.5 times lower than that of the latter (0.4 mg/kg/week compared to 1 mg/kg/week). Empty PEG-PLA NS and NC were devoid of antiuterotrophic and antitumoral activities. Altogether, these results suggest that the incorporation of the pure antiestrogen RU into long-circulating NP could represent a novel antiestrogen drug delivery system for the parenteral route.

Animals↗

PubMed2003

Conversion of hexadecanoic acid to hexadecenoic acid by rat Delta 6-desaturase.

A higher content of C16:1 n-10 has recently been reported in the preputial gland of mice with a targeted disruption of the gene encoding stearoyl-CoA desaturase 1 (SCD1-/- mice) when compared with wild-type mice. This result has provided the first physiological evidence for the presence and regulation of a palmitoyl-CoA Delta 6-desaturase in mammals. To investigate the putative involvement of the known Delta 6-desaturase (FADS2) in this process, COS-7 cells expressing rat Delta 6-desaturase were incubated with C16:0. Transfected cells were able to synthesize C16:1 n-10, while nontransfected cells did not produce any C16:1 n-10. Evidence is therefore presented that the rat Delta 6-desaturase, which acts on the 18- and 24-carbon fatty acids of the n-6 and n-3 series, is also able to catalyze palmitic acid Delta 6 -desaturation.

Animals↗

PubMed2003

Polyester-poly(ethylene glycol) nanoparticles loaded with the pure antiestrogen RU 58668: physicochemical and opsonization properties.

PURPOSE: The pure antiestrogen RU58668 (RU) was encapsulated within nanospheres (NS) and nanocapsules (NC) prepared from different polyester copolymers with poly(ethylene glycol) (PEG) chains. The influence of their physicochemical properties on drug release in vitro and their susceptibility to opsonization were evaluated. METHODS: RU-loaded PEG-bearing nanoparticles (NP) prepared by interfacial deposition of preformed polymer were characterized (size, zeta potential, percentage encapsulation and loading). In vitro release kinetics were studied in the presence of 10% fetal calf serum (FCS). Their opsonization in mouse serum was evaluated by silver staining of SDS-PAGE and Western blotting of desorbed proteins. RESULTS: The NS were smaller than NC and had a zeta potential close to zero and a higher percentage of loading. RU release from NS in vitro was reduced as compared with the dissolution profile of free RU in a serum-containing medium. Decreased opsonin adsorption at the surface of pegylated NS was observed. CONCLUSION: Small nanoparticulate systems containing a high load of pure antiestrogen, showing reduced drug release, have been developed. Among the six nanosphere preparations containing RU, two show a size below 200 nm, and two others undergo reduced protein adsorption in the presence of serum, compatible with increased persistence in the blood.

Animals↗

PubMed2003

Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B.

The aim of the present study was to evaluate the toxicity and the activity of a new lipid complex formulation of amphotericin B (AMB) (LC-AMB; dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, and AMB) that can be produced by a simple process. Like other lipid formulations, this new complex reduced both the hemolytic activity of AMB (the concentration causing 50% hemolysis of human erythrocytes, >100 microg/ml) and its toxicity toward murine peritoneal macrophages (50% inhibitory concentration, >100 microg/ml at 24 h). The in vivo toxicity of the new formulation (50% lethal dose, >200 mg/kg of body weight for CD1 mice) was similar to those of other commercial lipid formulations of AMB. The complex was the most effective formulation against the DD8 strain of Leishmania donovani. It was unable to reverse the resistance of an AMB-resistant L. donovani strain. In vivo LC-AMB was less efficient than AmBisome against L. donovani.

Amphotericin B↗

PubMed2002

The same rat Delta6-desaturase not only acts on 18- but also on 24-carbon fatty acids in very-long-chain polyunsaturated fatty acid biosynthesis.

The recently cloned Delta6-desaturase is known to catalyse the first step in very-long-chain polyunsaturated fatty acid biosynthesis, i.e. the desaturation of linoleic and alpha-linolenic acids. The hypothesis that this enzyme could also catalyse the terminal desaturation step, i.e. the desaturation of 24-carbon highly unsaturated fatty acids, has never been elucidated. To test this hypothesis, the activity of rat Delta6-desaturase expressed in COS-7 cells was investigated. Recombinant Delta6-desaturase expression was analysed by Western blot, revealing a single band at 45 kDa. The putative involvement of this enzyme in the Delta6-desaturation of C(24:5) n-3 to C(24:6) n-3 was measured by incubating transfected cells with C(22:5) n-3. Whereas both transfected and non-transfected COS-7 cells were able to synthesize C(24:5) n-3 by elongation of C(22:5) n-3, only cells expressing Delta6-desaturase were also able to produce C(24:6) n-3. In addition, Delta6-desaturation of [1-(14)C]C(24:5) n-3 was assayed in vitro in homogenates from COS-7 cells expressing Delta6-desaturase or not, showing that Delta6-desaturase catalyses the conversion of C(24:5) n-3 to C(24:6) n-3. Evidence is therefore presented that the same rat Delta6-desaturase catalyses not only the conversion of C(18:3) n-3 to C(18:4) n-3, but also the conversion of C(24:5) n-3 to C(24:6) n-3. A similar mechanism in the n-6 series is strongly suggested.

Animals↗