Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis.
Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis.
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长链多不饱和脂肪酸合成中的延伸酶反应作为控制点。
DOI：
10.1371/journal.pone.0029662
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
James MJ
中科院分区：
文献类型：
--
作者：
Gregory MK;Gibson RA;Cook-Johnson RJ;Cleland LG;James MJ
Δ6-去饱和酶 (Fads2) 被广泛认为是膳食 α-亚麻酸 (18:3n-3; ALA) 转化为长链 omega-3 多不饱和脂肪酸二十二碳六烯酸 (22:6n-3; DHA) 的限速剂。然而，增加膳食 ALA 或直接 Fads2 产物十八碳四烯酸（18:4n-3；SDA）会增加二十碳五烯酸（20:5n-3；EPA）和二十二碳五烯酸（22:5n-3；DPA）的组织水平，但不会增加 DHA。这些观察结果表明，除了 Fads2 的 ALA 代谢之外，还必须存在一个或多个控制点。一个可能的控制点是涉及 Fads2 本身的第二个反应，因为这种酶催化 24:5n-3 到 24:6n-3 的去饱和，以及 ALA 到 SDA 的去饱和。然而，EPA和DPA的代谢都需要延伸反应。本研究检查了两种延长酶的活性以及 Fads2 的第二个反应，以便集中研究 EPA 到 DHA 的代谢。在酵母中表达酶后，测定了大鼠延伸酶、Elovl2和Elovl5的底物选择性、竞争性底物相互作用和剂量响应曲线。还检查了大鼠 Fads2 的竞争性底物相互作用。大鼠 Elovl2 对 C20 和 C22 多不饱和脂肪酸具有活性，并且该单一酶催化 EPA→DPA→24:5n-3 的连续延伸反应。第二个反应 DPA→24:5n-3 在底物浓度下似乎是饱和的，而第一个反应 EPA→DPA 则不饱和。 ALA 剂量依赖性地抑制 Fads2 从 24:5n-3 到 24:6n-3 的转化。 ALA 和 24:5n-3 之间对 Fads2 的竞争可以解释在超过某些膳食 ALA 摄入量后观察到的 DHA 水平下降。此外，第二个 Elovl2 反应 DPA→24:5n-3 的表观饱和为饮食中提供 ALA、SDA 或 EPA 时 DPA 的积累提供了进一步的解释。这项研究表明，Elovl2 对于了解是否可以通过饮食方式增加 DHA 合成至关重要。
Δ6-Desaturase (Fads2) is widely regarded as rate-limiting in the conversion of dietary α-linolenic acid (18:3n-3; ALA) to the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (22:6n-3; DHA). However, increasing dietary ALA or the direct Fads2 product, stearidonic acid (18:4n-3; SDA), increases tissue levels of eicosapentaenoic acid (20:5n-3; EPA) and docosapentaenoic acid (22:5n-3; DPA), but not DHA. These observations suggest that one or more control points must exist beyond ALA metabolism by Fads2. One possible control point is a second reaction involving Fads2 itself, since this enzyme catalyses desaturation of 24:5n-3 to 24:6n-3, as well as ALA to SDA. However, metabolism of EPA and DPA both require elongation reactions. This study examined the activities of two elongase enzymes as well as the second reaction of Fads2 in order to concentrate on the metabolism of EPA to DHA. The substrate selectivities, competitive substrate interactions and dose response curves of the rat elongases, Elovl2 and Elovl5 were determined after expression of the enzymes in yeast. The competitive substrate interactions for rat Fads2 were also examined. Rat Elovl2 was active with C20 and C22 polyunsaturated fatty acids and this single enzyme catalysed the sequential elongation reactions of EPA→DPA→24:5n-3. The second reaction DPA→24:5n-3 appeared to be saturated at substrate concentrations not saturating for the first reaction EPA→DPA. ALA dose-dependently inhibited Fads2 conversion of 24:5n-3 to 24:6n-3. The competition between ALA and 24:5n-3 for Fads2 may explain the decrease in DHA levels observed after certain intakes of dietary ALA have been exceeded. In addition, the apparent saturation of the second Elovl2 reaction, DPA→24:5n-3, provides further explanations for the accumulation of DPA when ALA, SDA or EPA is provided in the diet. This study suggests that Elovl2 will be critical in understanding if DHA synthesis can be increased by dietary means.
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影响因子：
6.5
作者：
Blank, C;Neumann, MA;Gibson, RA
通讯作者：
Gibson, RA
影响因子：
1.6
作者：
Inagaki, K;Aki, T;Suzuki, O
通讯作者：
Suzuki, O
影响因子：
7.1
作者：
Pawlosky, RJ;Hibbeln, JR;Salem, N
通讯作者：
Salem, N
DOI：
10.1016/j.cbpb.2009.11.002
发表时间：
2010-02-01
影响因子：
2.2
作者：
Gregory, Melissa K.;See, Valene H. L.;Schuller, Kathryn A.
通讯作者：
Schuller, Kathryn A.
DOI：
10.1006/bbrc.1999.0235
发表时间：
1999-02-24
影响因子：
3.1
作者：
Aki, T;Shimada, Y;Suzuki, O
通讯作者：
Suzuki, O