DHA の構造的意味

抄録

Docosahexaenoic acid（C22 :6n-3, DHA）plays a special role in biological membrane dynamics, and especially affects human health and various diseases. I try to review the structural significance of DHA in two points, membrane dynamics and oxidative metabolites, to realize the action mechanisms of DHA on health and diseases. It has been believed that polyunsaturated fatty acids, such asarachidonic acid（C20 :4n-6）and DHA, in bio-membranes may increase fluidity ofthe membrane（ “fluidity hypothesis”）and thus modulate mobility of membrane proteins, however, it is proved recently that the fluidity hypothesis is not always true for DHA. It has been shown that DHA could have quite various conformationsunder physiological conditions for free or ester forms, as determined by simulations and X-ray crystallography of DHA-bound proteins, and this high flexibility of DHA conformation may be a key point to realize the action mechanism of DHA-containing phospholipids on membrane dynamics with high resilience andadaptability（ “flexibility hypothesis”）. With this“flexibility hypothesis”, it could be uniformly recognized how DHA is important for rapid membrane dynamics（fission and fusion）, for lipid-receptors interactions, for modulation of lipid raft size, and for regulation of nuclear receptors and expression of genes. The reason why DHA is enriched in retina, brain, testes, and heart, which tissues are all active in membrane dynamics and oxygen metabolism, may be realized with the flexibility hypothesis. The second point, why DHA is metabolized to quite variousoxidative/oxygenative derivatives（docosanoids）, may be realized under the view of whole oxylipin metabolism including eicosanoids. Oxylipin metabolism is recently summarized as oxygenated polyunsaturated fatty acids, however, it may be more rational to categorize“Oxylipin”as oxidative metabolites of lipids widely including terpenoids, to realize the structural resemblance between DHA and retinoids, and the function of medium chain oxygenated fatty acid metabolites. The view of co-regulation in various oxylipin metabolites including docosanoids and eicosanoids may be needed for realizing the fine regulation mechanism of active tissue metabolism and pathophysiology. The structure-based theory of the effect of DHA and its oxidative metabolites on bio-membrane dynamics and lipid-protein interactions may help largely to realize the action-mechanism of DHA on human health and diseases. Key words: docosahexaenoic acid（DHA）, flexibility hypothesis, fluidity hypothesis, membrane dynamics, oxylipin.