Fatty acid desaturation and chain elongation in eukaryotes

Cook, Harold W.

doi:10.1016/s0167-7306(08)60512-8

Cited by 196 publications

(170 citation statements)

References 18 publications

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“…The involvement of cytochrome b & in the reaction of the nk6 oleate desaturase agrees with this cytochrome acting as an electron carrier for many fatty acid desaturases [37,43]. However, because only a single low-molecular-mass (13 kDa) Acanthamoeba castellanii protein reacted with the anti-(cytochrome b & ) antibody, and because cytochrome b & levels were unaffected by oxygen induction (when desaturation was increased), then we have no evidence for a fused cytochrome b & -desaturase protein, as reported for a number of systems recently [44,45].…”

Section: Discussionsupporting

confidence: 65%

“…fatty acids, which were consistent with an increase in nk6 fatty acid desaturation. Thus some nk9,12-eicosadienoate appeared to be converted into nk6,9,12-eicosatrienoate, and the level of arachidonate was increased, presumably as a result of the extra availability of its metabolic precursor (dihomo-γ-linolenic acid) [37]. These changes, which were induced by oxygen alone, mimicked very closely those induced by low temperature [9,10], and could be explained fully by induction of nk6 fatty acid desaturase activity.…”

Section: Oxygen Levels Correlate With Increased Unsaturationmentioning

confidence: 72%

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Oxygen induction of a novel fatty acid n−6 desaturase in the soil protozoon, Acanthamoeba castellanii

Rutter

Thomas

Herbert

et al. 2002

Biochemical Journal

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Induction of fatty acid desaturation is very important for the temperature adaptation of poikilotherms. However, in oxygen-limited late-exponential-phase Acanthamoebacastellanii cultures, oxygen alone was able to induce increased activity of a fatty acid desaturase that converts oleate into linoleate and which has been implicated in the temperature adaptation of this organism. Experiments with Δ10-nonadecenoate showed that the enzyme is an n-6 desaturase rather than a Δ12-desaturase. It also used preferentially 1-acyl-2-oleoyl-phosphatidylcholine as substrate and NAD(P)H as electron donor. The involvement of cytochrome b5 as an intermediate electron carrier was shown by difference spectra measurements and anti-(cytochrome b5) antibody experiments. Of the three protein components of the desaturase complex, oxygen only increased the activity of the terminal (cyanide-sensitive) protein during n-6 desaturase induction. The induction of this terminal protein paralleled well the increase in overall oleate n-6 desaturation. The ability of oxygen to induce oleate desaturase independently of temperature in this lower eukaryotic animal model is of novel intrinsic interest, as well as being important for the design of future experiments to determine the molecular mechanism of temperature adaptation in poikilotherms.

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Section: Discussionsupporting

confidence: 65%

Section: Oxygen Levels Correlate With Increased Unsaturationmentioning

confidence: 72%

Oxygen induction of a novel fatty acid n−6 desaturase in the soil protozoon, Acanthamoeba castellanii

Rutter

Thomas

Herbert

et al. 2002

Biochemical Journal

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“…Synthesis of EPA requires Δ6 desaturation of 18:3n-3 to produce 18:4n-3 that is elongated to 20:4n-3 followed by Δ5 desaturation to produce EPA (Cook, 1996). This is essentially the pathway investigated in most early studies in relation to synthesis of HUFA in vertebrates, more specifically 20:4n-6, and the rate-limiting step was found to be the Δ6 desaturation (Brenner, 1974).…”

Section: Discussionmentioning

confidence: 98%

“…Synthesis of EPA is achieved by Δ6 desaturation of 18:3n-3 to produce 18:4n-3 that is elongated to 20:4n-3 followed by Δ5 desaturation (Cook, 1996), with synthesis of DHA from EPA requiring two further elongation steps, a second Δ6 desaturation and a peroxisomal chain shortening step (Sprecher, 2000). Evidence suggests that the dependence of marine fish on dietary HUFA is caused by a deficiency in the activity of one or more of the key enzymes in this pathway (Tocher, 2003).…”

Section: Introductionmentioning

confidence: 99%

Physiological roles of fatty acyl desaturases and elongases in marine fish: Characterisation of cDNAs of fatty acyl Δ6 desaturase and elovl5 elongase of cobia (Rachycentron canadum)

et al. 2009

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In the present paper, we investigated the expression of fatty acyl desaturase and elongase genes in a marine teleost, cobia, a species of great interest due to its considerable aquaculture potential. A cDNA was cloned that, when expressed in yeast, was shown to result in desaturation of 18:3n-3 and 18:2n-6, indicating that it coded for a Δ6 desaturase enzyme. Very low desaturation of 20:4n-3 and 20:3n-6 indicated only trace Δ5 activity. Another cloned cDNA enabled elongation of 18:4n-3, 18:3n-6, 20:5n-3 and 20:4n-6 in the yeast expression system, indicating that it had C18-20 and C20-22 elongase activity. Sequence comparison and phylogenetic analysis confirmed that it was homologous to human ELOVL5 elongase. However, the cobia Elovl5 elongase also had low activity toward C24 HUFA. The cobia Δ6 desaturase had a preference for 18:3n-3, but the elongase was generally equally active with both n-3 and n-6 substrates. Expression of both genes was 1-2 orders of magnitude greater in brain than other tissues suggesting an important role, possibly to ensure sufficient docosahexaenoic acid (DHA, 22:6n-3) synthesis in neural tissues through elongation and desaturation of eicosapentaenoic acid (EPA; 20:5n-3).3

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“…However, many vertebrates can convert dietary 18:2n-6 and 18:3n-3 to long chain, highly unsaturated fatty acids (HUFA) such as arachidonic acid (20:4n-6, AA), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (22:6n-3, DHA) via a pathway involving a series of microsomal fatty acid desaturation and elongation steps ( Fig.1) (Cook, 1996). The production of EPA requires Δ6 and Δ5 desaturases, and the production of DHA from EPA requires a further desaturation originally thought to be effected by a Δ4 desaturase acting on a C 22 fatty acid intermediate, although evidence now suggests it may actually be effected by a Δ6 desaturase acting on a C 24 intermediate (Sprecher, 2000;de Antueno et al, 2001;D'Andrea et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Characterization and comparison of fatty acyl Δ6 desaturase cDNAs from freshwater and marine teleost fish species

Zheng

Seiliez

Hastings

et al. 2004

Comparative Biochemistry and Physiology Part B: Biochemistry an

173

139

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Abstract:Fish are the most important dietary source of the n-3 highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), that have particularly important roles in human nutrition reflecting their roles in critical physiological processes. The objective of the study described here was to clone, functionally characterise and compare expressed fatty acid desaturase genes involved in the production of EPA and DHA in freshwater and marine teleost fish species.Putative fatty acid desaturase cDNAs were isolated and cloned from common carp (Cyprinus carpio) and turbot (Psetta maximus). The enzymic activities of the products of these cDNAs, together with those of cDNAs previously cloned from rainbow trout (Oncorhynchus mykiss) and gilthead seabream (Sparus aurata), were determined by heterologous expression in the yeast containing the haem-binding motif, HPGG. Functional expression showed all four fish cDNAs encode basically unifunctional Δ6 fatty acid desaturase enzymes responsible for the first and ratelimiting step in the biosynthesis of HUFA from 18:3n-3 and 18:2n-6. All the fish desaturases were more active towards the n-3 substrate with 59.5%, 31.5%, 23.1% and 7.0% of 18:3n-3 being converted to 18:4n-3 in the case of turbot, trout, seabream and carp, respectively. The enzymes also showed very low, probably physiologically insignificant, levels of Δ5 desaturase activity, but none of the products showed Δ4 desaturase activity. The cloning and characterisation of desaturases from these fish is an important advance, as they are species in which there is a relative wealth of data on the nutritional regulation of fatty acid desaturation and HUFA synthesis, and between which substantive differences occur.

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Fatty acid desaturation and chain elongation in eukaryotes

Cited by 196 publications

References 18 publications

Oxygen induction of a novel fatty acid n−6 desaturase in the soil protozoon, Acanthamoeba castellanii

Oxygen induction of a novel fatty acid n−6 desaturase in the soil protozoon, Acanthamoeba castellanii

Physiological roles of fatty acyl desaturases and elongases in marine fish: Characterisation of cDNAs of fatty acyl Δ6 desaturase and elovl5 elongase of cobia (Rachycentron canadum)

Characterization and comparison of fatty acyl Δ6 desaturase cDNAs from freshwater and marine teleost fish species

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