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Transport, Synthesis, and Incorporation of n–3 and n–6 Fatty Acids in Brain Glycerophospholipids

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Neural membranes are composed of glycerophospholipids, sphingolipids, cholesterol, and proteins. Glycerophospholipids and sphingolipids contain nonpolar fatty acyl, alkenyl, and alkyl chains. The degree of unsaturation in polyunsaturated fatty acids (PUFA) determines many neural membrane properties including membrane order, packing pattern, and fluidity. Variations in the head group, length of the fatty acid acyl chains, and degree of saturation and unsaturation produce changes in surface charge and physicochemical characteristics of neural membranes. Collective evidence suggests that PUFA modulate many neural membrane properties and functions (Yehuda et al., 2002; Farooqui and Horrocks, 2007; Farooqui, 2009). Three families of PUFA are known to occur in neural membranes: the n–3 PUFA family is characterized by having their first double bond at carbon atom number 3; n–6 PUFA family members have their first double bond at carbon atom number 6, when counted from the methyl end of the carbon chain; and n–9 family member contains first double bond at carbon atom number 9 from fatty acid methyl end. Examples of n–3 fatty acids are α-linolenic acid (ALA; 18:3n–3) acid, eicosapentaenoic acid (EPA; 20:5n–3), and docosahexaenoic acid (DHA; 22:6n–3). Examples of n–6 fatty acid family are linoleic acid (LA; 18:2n–6), arachidonic acid (ARA; 20:4n–6), and adrenic acid (AA; 22:4n–6), and example of n–9 family is oleic acid. Mammals cannot introduce double bond between carbon 1 and 6 due to the lack of desaturases but can introduce a double bond after the ninth carbon through the action of Δ9-desaturase. In mammalian synaptosomal plasma membrane glycerophospholipids, n–6 and n–3 PUFA are mainly located at the sn-2 position of glycerol moiety. Majority of ARA and oleic acid is associated with phosphatidylcholine (PtdCho), whereas phosphatidylethanolamine (PtdEtn) and ethanolamine plasmalogens (PlsEtn) contain both ARA and DHA at the sn-2 position of glycerol moiety. Phosphatidylserine (PtdSer) is enriched in DHA (Glomset, 2006). Sphingomyelin and glycolipids in synaptosomal plasma membranes contain amide-linked stearic acid instead of a mixture of this acid with other amide-linked fatty acids. Although the physiological significance of this unique distribution of lipid head groups, esterified fatty acids, and amide-linked fatty acids is not fully understood, asymmetric distribution of glycerophospholipids and sphingolipids between the two leaflets of neural membrane may contribute to dynamic lipid substructures (Glomset, 2006). In neural membranes, DHA and ARA are substrates for lipid mediators. LA and ALA are precursors for the synthesis of ARA and DHA, respectively. The importance of ARA and DHA is related to their specific interactions with membrane proteins and their ability to serve as precursors for eicosanoids and docosanoids. Collective evidence suggests that the incorporation of ARA and DHA in neural membranes not only induces changes in physicochemical properties of membranes but also modulates membrane functions through the generation of lipid mediators (Horrocks and Farooqui, 2004).

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  1. Department of Molecular and Cellular Biochemistry, The Ohio State University, 43210, Columbus, OH, USA

    Akhlaq A. Farooqui

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Farooqui, A.A. (2009). Transport, Synthesis, and Incorporation of n–3 and n–6 Fatty Acids in Brain Glycerophospholipids. In: Beneficial Effects of Fish Oil on Human Brain. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0543-7_2

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