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F Sargueil

Publications and source records attributed to F Sargueil.

7 recordsLinked to original sources

Phosphatidylserine increase in rat liver endomembranes during the acute phase response.

The acute phase response (APR) is responsible for great changes in protein and lipid metabolism. For example, marked changes are observed in the metabolism of fatty acids, triglycerides, cholesterol and sphingolipids. Those lipids are partly recovered in the lipoproteins and subsequently in the plasma. Beside these lipid families, nothing is known about phospholipids and their synthesis in endomembranes during the APR. Our studies show that phosphatidylserine synthesis is stimulated during the APR and that this lipid is increased in the endoplasmic reticulum (ER) and the ER-derived vesicles.

Acute-Phase Reaction↗

Peroxisomal beta-oxidation enzyme gene expression in the developing mouse brain.

Using the northern blot technique, the steady-state levels for the mRNAs encoding acyl-CoA oxidase, pristanoyl-CoA oxidase, trans2, 3enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase multifunctional enzyme type 2, 3-ketoacyl-CoA thiolase and sterol-carrier-protein x during postnatal brain development were measured. The developmental patterns obtained for each mRNA species studied were similar, with an increase in the mRNA level between birth and postnatal day 5, followed by a gradual decrease to 34-55% of the maximal value at postnatal day 30. These results are in agreement with a coordinately controlled expression of the genes involved in VLCFA beta-oxidation during brain development. Moreover, comparison of these developmental profiles with that obtained for ceramide galactosyltransferase showed that the set-up of the very-long-chain fatty acids beta-oxidation system is independent of the myelinating signal in the central nervous system.

3-Hydroxyacyl CoA Dehydrogenases↗

Myelin synthesis in the peripheral nervous system.

By imposing saltatory conduction on the nervous impulse, the principal role of the myelin sheath is to allow the faster propagation of action potentials along the axons which it surrounds. Peripheral nervous system (PNS) myelin is formed by the differentiation of the plasma membrane of Schwann cells. One of the biochemical characteristics that distinguishes myelin from other biological membranes is its high lipid-to-protein ratio. All the major lipid classes are represented in the myelin membrane, while several myelin-specific proteins have been identified. During development, the presence of axons is required for the initiation of myelination, but the nature of the axonal signal is still unknown. The only certainties are that this signal is synthesized by axons whose diameter is greater than 0.7 microm, and that the signal(s) include(s) a diffusible molecule. Morphological studies have provided us with information concerning the timing of myelination, the mechanism by which immature Schwann cells differentiate into a myelinating phenotype and lay down the myelin sheath around the axon, and the accumulation and the structure of the myelin membrane. The last 20 years have seen the identification and the cDNA and gene cloning of the major PNS myelin proteins, which signalled the beginning of the knock-out decade: transgenic null-mutant mice have been created for almost every protein gene. The study of these animals shows that the formation of myelin is considerably less sensitive to molecular alterations than the maintenance of myelin. During the same period, important data has been gathered concerning the synthesis and function of lipids in PNS myelin, although this field has received relatively little attention compared with that of their protein counterparts.

Animals↗

Gene expression of peroxisomal beta-oxidation enzymes in rat brain.

Despite increasing insight into peroxisomal beta-oxidation, it is still not clear which enzymes catalyze very-long-chain fatty acid degradation. Using the northern blot and RT-PCR techniques, a brain-specific expression is demonstrated for acyl-CoA oxidase 3II mRNA, thiolase-A and trans2,3enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase multifunctional enzyme type 2.

17-Hydroxysteroid Dehydrogenases↗

High metabolism and subsequent elongation of 3-hydroxyeicosanoyl-CoA in very-long-chain fatty acid deficient PNS of Trembler mice.

The developmental patterns of the overall fatty acid elongation and of the last two partial activities of microsomal elongase (dehydration and reduction of 3-hydroxyacyl-CoA) were investigated in the PNS of normal and Trembler mice. Unexpectedly, Trembler microsomes synthesized normal C22-CoA amounts from 3-hydroxyeicosanoyl-CoA (3-OHC20-CoA), a C18-CoA elongation intermediate. Hydroxy- acyl-CoA dehydrase and enoyl-CoA reductase activities were found to be higher in the mutant than in the control, whatever the stage of development. Moreover, C20-CoA elongation led to normal C22-CoA and C24-CoA formation in the mutant whereas C20-CoA formation from C18-CoA was always far lower in Trembler than in control. C18-CoA condensing enzyme emerges as the only elongation step involved in the VLCFA deficit evidenced in Trembler PNS.

Acyl Coenzyme A↗

Hydroxyacyl-CoA dehydrase and trans-2,3-enoyl-CoA reductase activities are consistent with long-chain fatty acid accumulation during rat brain development.

The developmental changes of microsomal 3-hydroxyacyl-CoA dehydrase and trans-2,3-enoyl-CoA reductase activities were analyzed and compared to very-long-chain fatty acid content and biosynthesis in rat brain. Contrary to the elongation rate of eicosanoyl-CoA and 3-hydroxyeicosanoyl-CoA, which paralleled myelination during brain maturation, the two partial activities of fatty acid elongation were already present at the earliest stages of development. One day after birth, 3-hydroxyacyl-CoA dehydrase and trans-2,3-enoyl-CoA reductase specific activities already represented 54.8% and 49.6% of the adult values, respectively. As a contribution to the quantitative estimation of the brain's ability to form its own VLCFA, it is shown that dehydrase and reductase activities are sufficient to allow the biosynthesis of all rat brain VLCFA at any age.

Acyl-CoA Dehydrogenases↗

Dehydration of 3-hydroxyacyl-CoA in brain very-long-chain fatty acid synthesis.

Rat brain microsomes actively dehydrate 3-hydroxyacyl-CoAs. Using chemically synthesized [1-(14)C] (R,S) 3-hydroxyeicosanoyl-CoA, we investigated the biochemical characteristics of the dehydration and reduction steps of stearoyl-CoA elongation. The reaction products, separated and identified as trans2,3-enoyl-CoAs and, in the presence of NADPH, as saturated acyl-CoAs, were released from the enzyme as thioesters which were partly hydrolysed. A kinetic analysis of the two coupled reactions showed that the 3-hydroxyacyl-CoA dehydrase catalysed a reversible reaction with kinetic constants of about 0.045 min(-1) for forward reaction (dehydration) and 0.025 min(-1) for reverse reaction (hydration); Vmax of the dehydration reached 20 nmoles/min/mg and the apparent Km was 44 microM. In the presence of NADPH, the kinetic constants for the dehydrase were unchanged and that for the trans2,3-enoyl-CoA reductase was 0.025 min(-1). The relative proportion of trans2,3-enoyl-CoA and saturated acyl-CoA depended on the protein amount. An inhibition of the reduction step was observed for substrate concentrations above 15 microM. The 3-hydroxyacyl-CoA dehydrase used (R) rather than (S) 3-hydroxyacyl-CoA. Furthermore, the elongation of (R) 3-hydroxyeicosanoyl-CoA yielded saturated very-long-chain acyl-CoA. These results demonstrated that 3-hydroxyacyl-CoAs entered the elongating complex exclusively at the level of the dehydrase and not of the condensing enzyme.

Acyl-CoA Dehydrogenases↗