N-3 polyunsaturated fatty acids (PUFA) and the numerous families of lipid mediators derived from them collectively regulate numerous biological processes. The mechanisms by which n-3 PUFA regulate biological processes begins with an understanding of the n-3 biosynthetic pathway that starts with alpha-linolenic acid (18:3n-3) and is commonly thought to end with the production of docosahexaenoic acid (DHA, 22:6n-3). However, our understanding of this pathway is not as complete as previously believed. In the current review we provide a background of the evidence supporting the pathway as currently understood and provide updates from recent studies challenging three central dogma of n-3 PUFA metabolism. By building on nearly three decades of research primarily in cell culture and oral dosing studies, recent evidence presented focuses on in vivo kinetic modelling and compound-specific isotope abundance studies in rodents and humans that have been instrumental in expanding our knowledge of the pathway. Specifically, we highlight three main updates to the n-3 PUFA biosynthesis pathway: (1) DHA synthesis rates cannot be as low as previously believed, (2) DHA is both a product and a precursor to tetracosahexaenoic acid (24:6n-3) and (3) increases in EPA in response to DHA supplementation are not the result of increased retroconversion.

N-3多不饱和脂肪酸（PUFA）和衍生自它们的众多脂质介体家族共同调控着许多生物过程。n-3 PUFA调节生物过程的机制始于对n-3生物合成途径的了解，该途径始于α-亚麻酸（18：3n-3），通常被认为以二十二碳六烯酸（DHA）的生产结束，22：6n-3）。但是，我们对这种途径的理解并不像以前认为的那样完整。在当前的综述中，我们提供了支持该途径的证据的背景，并且目前提供了挑战n-3 PUFA代谢的三个中心教条的最新研究的最新进展。通过对细胞培养和口服剂量研究的近三十年研究的基础上，最近提出的证据集中在在啮齿动物和人类中进行的体内动力学建模和化合物特异性同位素丰度研究对扩大我们对该途径的了解起到了重要作用。具体来说，我们重点介绍了n-3 PUFA生物合成途径的三个主要更新：（1）DHA的合成速率不能像以前认为的那么低，（2）DHA既是四二十碳六烯酸的产物又是其前体（24：6n-3 ）和（3）响应DHA补充而增加的EPA并不是逆转转化增加的结果。