The fatty acid chain elongation system of mammalian endoplasmic reticulum

Cinti, Dominick L.; Cook, Lynda; Nagi, Mahmod N.; Suneja, Sanoj K.

doi:10.1016/0163-7827(92)90014-a

Cited by 224 publications

(161 citation statements)

References 306 publications

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“…The first step is a condensation reaction of the precursor fatty acyl chain with malonyl-CoA to produce a β-ketoacyl chain that is subsequently hydrogenated in three successive steps. This first condensation step determines the substrate specificity and is the rate-limiting step of the process and is therefore regarded as being the actual "elongase" enzyme-effected step (Cinti et al, 1992). Previous work on the regulation of the HUFA biosynthesis pathway has tended to focus on the desaturase enzymes as the points of regulation (Brenner, 1981).…”

Section: Discussionmentioning

confidence: 99%

Effects of diets containing vegetable oil on expression of genes involved in highly unsaturated fatty acid biosynthesis in liver of Atlantic salmon (Salmo salar)

et al. 2004

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Fish are an important dietary source of the long-chain C 20 and C 22 highly unsaturated fatty acids (HUFA), arachidonate (20:4n-6), eicosapentaenoate (20:5n-3) and docosahexaenoate (22:6n-3), that are crucial to the health of higher vertebrates and that can be beneficial in human diets. Δ5 and Δ6 fatty acid desaturases, and fatty acid elongases are critical enzymes in the biosynthetic pathways of HUFA from shorter chain C 18 polyunsaturated fatty acids (PUFA) such as linoleic (18:2n-6) and α-linolenic (18:3n-3) acids. Recently, full-length cDNAs for fatty acid desaturase and elongase enzymes have been cloned from Atlantic salmon. Functional characterisation of the desaturase revealed n-3 Δ5 desaturase activity, whereas the elongase had broad substrate specificity for PUFA with a range of chain lengths from C 18 to C 22 . The study described here was primarily focused on the nutritional regulation of genes involved in the HUFA biosynthetic pathway in Atlantic salmon. A feeding trial was performed whereby salmon smolts in seawater pens were fed for 40 weeks on five different diets. The diets consisted of a control diet containing fish oil (FO) and four diets in which the FO was replaced in a graded manner by linseed oil (LO). Specifically, in terms of added oils, the five diets were 100% FO (FO), 100%LO (LO100) and FO/LO in ratios of 3:1 (LO25), 1:1 (LO50) and 1:3 (LO75). Fish were sampled at 20 and 40 weeks, and samples of liver were collected for lipid analyses and total RNA extraction. Hepatocytes were also prepared and the activity of the HUFA biosynthetic pathway determined. Expression of fatty acid desaturase and elongase genes was determined by quantitative real time PCR and the ratio of the copy number of the targeted gene against that of β-actin was calculated. The results showed that after 20 weeks of feeding, desaturase and elongase gene expression in liver was increased in a graded manner by increasing dietary LO. Expression of both genes was positively and negatively correlated with dietary 18:3n-3 and n-3 HUFA, respectively. By 40 weeks of feeding, expression of neither gene showed the same degree of correlation with dietary fatty acid composition. In contrast, activity of the HUFA biosynthetic pathway, which showed some association with diet at 20 weeks, was positively and significantly correlated with dietary LO after 40 weeks of feeding. Elongation activity reflected the overall activity of the HUFA biosynthetic pathway to a greater degree than Δ5 desaturation activity. The possible mechanisms underlying the observed results and the regulation of the HUFA biosynthetic pathway are discussed.3

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Section: Discussionmentioning

confidence: 99%

Effects of diets containing vegetable oil on expression of genes involved in highly unsaturated fatty acid biosynthesis in liver of Atlantic salmon (Salmo salar)

et al. 2004

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“…The first reaction involves condensation of malonyl-CoA with a long chain acyl substrate producing a 3-ketoacyl-CoA, catalyzed by 3-ketoacyl-CoA synthase (KCS). Subsequent reactions include reduction to 3-hydroxyacyl-CoA catalyzed by 3-ketoacyl-CoA reductase (KCR) and dehydration to an enoyl-CoA by 3-hydroxyacylCoA dehydratase, followed by a second reduction catalyzed by trans-2-enoyl-CoA reductase to form the elongated acyl-CoA [12]. A number of plant KCS(s) that are all specific to saturated and monounsaturated fatty acids have been identified and partially characterized [2].…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

et al. 2005

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Genes encoding enzymes involved in biosynthesis of very long chain fatty acids were significantly up-regulated during early cotton fiber development. Two cDNAs, GhKCR1 and GhKCR2 encoding putative cotton 3-ketoacyl-CoA reductases that catalyze the second step in fatty acid elongation, were isolated from developing cotton fibers. GhKCR1 and 2 contain open reading frames of 963 bp and 924 bp encoding proteins of 320 and 307 amino acid residues, respectively. Quantatitive RT-PCR analysis showed that both these genes were highly preferentially expressed during the cotton fiber elongation period with much lower levels recovered from roots, stems and leaves. GhKCR1 and 2 showed 30%-32% identity to Saccharomyces cerevisiae Ybr159p at the deduced amino acid level. These cotton cDNAs were cloned and expressed in yeast haploid ybr159w∆ mutant that was deficient in 3-ketoacyl-CoA reductase activity. Wild-type growth rate was restored in ybr159w∆ cells that expressed either GhKCR1 or 2. Further analysis showed that GhKCR1 and 2 were co-sedimented within the membranous pellet fraction after high-speed centrifugation, similar to the yeast endoplasmic reticulum marker ScKar2p. Both GhKCR(s) showed NADPH-dependent 3-ketoacyl-CoA reductase activity in an in vitro assay system using palmitoyl-CoA and malonyl-CoA as substrates. Our results suggest that GhKCR1 and 2 are functional orthologues of ScYbr159p.

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“…2). The first step essentially effects chain elongation by condensation of the activated fatty acid with malonyl-CoA (Cinti et al, 1992). This step is rate-limiting, and operates on substrates specified by a putative elongase polypeptide.…”

Section: Introductionmentioning

confidence: 99%

Zebrafish cDNA Encoding Multifunctional Fatty Acid Elongase Involved in Production of Eicosapentaenoic (20:5n-3) and Docosahexaenoic (22:6n-3) Acids

et al. 2004

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The fatty acid chain elongation system of mammalian endoplasmic reticulum

Cited by 224 publications

References 306 publications

Effects of diets containing vegetable oil on expression of genes involved in highly unsaturated fatty acid biosynthesis in liver of Atlantic salmon (Salmo salar)

Effects of diets containing vegetable oil on expression of genes involved in highly unsaturated fatty acid biosynthesis in liver of Atlantic salmon (Salmo salar)

Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

Zebrafish cDNA Encoding Multifunctional Fatty Acid Elongase Involved in Production of Eicosapentaenoic (20:5n-3) and Docosahexaenoic (22:6n-3) Acids

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