Human Fatty Acid Transport Protein 2a/Very Long Chain Acyl-CoA Synthetase 1 (FATP2a/Acsvl1) Has a Preference in Mediating the Channeling of Exogenous n-3 Fatty Acids into Phosphatidylinositol

Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 07/2011; 286(35):30670-9. DOI: 10.1074/jbc.M111.226316
Source: PubMed


The trafficking of fatty acids across the membrane and into downstream metabolic pathways requires their activation to CoA thioesters. Members of the fatty acid transport protein/very long chain acyl-CoA synthetase (FATP/Acsvl) family are emerging as key players in the trafficking of exogenous fatty acids into the cell and in intracellular fatty acid homeostasis. We have expressed two naturally occurring splice variants of human FATP2 (Acsvl1) in yeast and 293T-REx cells and addressed their roles in fatty acid transport, activation, and intracellular trafficking. Although both forms (FATP2a (M(r) 70,000) and FATP2b (M(r) 65,000 and lacking exon3, which encodes part of the ATP binding site)) were functional in fatty acid import, only FATP2a had acyl-CoA synthetase activity, with an apparent preference toward very long chain fatty acids. To further address the roles of FATP2a or FATP2b in fatty acid uptake and activation, LC-MS/MS was used to separate and quantify different acyl-CoA species (C14-C24) and to monitor the trafficking of different classes of exogenous fatty acids into intracellular acyl-CoA pools in 293T-REx cells expressing either isoform. The use of stable isotopically labeled fatty acids demonstrated FATP2a is involved in the uptake and activation of exogenous fatty acids, with a preference toward n-3 fatty acids (C18:3 and C22:6). Using the same cells expressing FATP2a or FATP2b, electrospray ionization/MS was used to follow the trafficking of stable isotopically labeled n-3 fatty acids into phosphatidylcholine and phosphatidylinositol. The expression of FATP2a resulted in the trafficking of C18:3-CoA and C22:6-CoA into both phosphatidylcholine and phosphatidylinositol but with a distinct preference for phosphatidylinositol. Collectively these data demonstrate FATP2a functions in fatty acid transport and activation and provides specificity toward n-3 fatty acids in which the corresponding n-3 acyl-CoAs are preferentially trafficked into acyl-CoA pools destined for phosphatidylinositol incorporation.

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    • "Fads1 fatty acid desaturase 1, Fads2 fatty acid desaturase 2, Elovl2 elongase 2, Elovl5 elongase 5, Scd1 stearoyl-CoA desaturase 1, Elovl6 elongase 6, Fatp2 fatty acid transport protein 2, Fatp3 fatty acid transport protein 3, Fatp4 fatty acid transport protein 4, Fatp5 fatty acid transport protein 5, Acsl6 acyl-CoA synthetase long-chain 6, Fat/cd36 fatty acid translocase/cluster of differentiation 36, Fabp1 fatty acid binding protein 1, Fabp5 fatty acid binding protein 5, Fabp7 fatty acid binding protein 7. Data are mean ± SEM; n = 6–7; *p \ 0.05 Fig. 3 FATP2 protein levels in fasted versus fed mice. Data are mean ± SEM; n = 4; *p \ 0.05 transporters preferentially mediate uptake of n-3 and n-6 PUFA into cells and show high affinity for 22:6n-3 (Norris and Spector 2002; Marszalek et al. 2005; Xu et al. 1996; Mita et al. 2010; Nemecz et al. 1991; Melton et al. 2011, 2013). Expression of the Fatp5 transporter was also 1.5- fold higher in fasted animals compared with ad libitum fed animals. "
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