Fatty acid transporter proteins (FATPs) are a family (SLC27) of six transporters (FATP1-6). They have at least one, and possibly six [5,11], transmembrane segments, and are predicted on the basis of structural similarities to form dimers. SLC27 members have several structural domains: integral membrane associated domain, peripheral membrane associated domain, FATP signature, intracellular AMP binding motif, dimerization domain, lipocalin motif, and an ER localization domain (identified in FATP4 only) [3,8-9]. These transporters are unusual in that they appear to express intrinsic very long-chain acyl-CoA synthetase (EC 6.2.1.- , EC 6.2.1.7) enzyme activity. Within the cell, these transporters may associate with plasma and peroxisomal membranes. FATP1-4 and -6 transport long- and very long-chain fatty acids, while FATP5 transports long-chain fatty acids as well as bile acids [1,7,11].

Although the stoichiometry of fatty acid transport is unclear, it has been proposed to be facilitated by the coupling of fatty acid transport to conjugation with coenzyme A to form fatty acyl CoA esters. Small molecule inhibitors of FATP2 [6,10] and FATP4 [2,13], as well as bile acid inhibitors of FATP5 [13], have been described; analysis of the mechanism of action of some of these inhibitors suggests that transport may be selectively inhibited without altering enzymatic activity of the FATP.

C1-BODIPY-C12 accumulation has been used as a non-selective index of fatty acid transporter activity.

FATP2 has two variants: Variant 1 encodes the full-length protein, while Variant 2 encodes a shorter isoform missing an internal protein segment. FATP6 also has two variants: Variant 2 encodes the same protein as Variant 1 but has an additional segment in the 5' UTR.

* Key recommended reading is highlighted with an asterisk

* Anderson CM, Stahl A. (2013) SLC27 fatty acid transport proteins. Mol Aspects Med, 34 (2-3): 516-28. [PMID:23506886]

* Dourlen P, Sujkowski A, Wessells R, Mollereau B. (2015) Fatty acid transport proteins in disease: New insights from invertebrate models. Prog Lipid Res, 60: 30-40. [PMID:26416577]

Gimeno RE. (2007) Fatty acid transport proteins. Curr Opin Lipidol, 18 (3): 271-6. [PMID:17495600]

* Schwenk RW, Holloway GP, Luiken JJ, Bonen A, Glatz JF. (2010) Fatty acid transport across the cell membrane: regulation by fatty acid transporters. Prostaglandins Leukot Essent Fatty Acids, 82 (4-6): 149-54. [PMID:20206486]

Stahl A. (2004) A current review of fatty acid transport proteins (SLC27). Pflugers Arch, 447 (5): 722-7. [PMID:12856180]

Watkins PA. (2008) Very-long-chain acyl-CoA synthetases. J Biol Chem, 283 (4): 1773-7. [PMID:18024425]

1. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

2. Blackburn C, Guan B, Brown J, Cullis C, Condon SM, Jenkins TJ, Peluso S, Ye Y, Gimeno RE, Punreddy S et al.. (2006) Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as inhibitors of the fatty acid transporter FATP4. Bioorg Med Chem Lett, 16 (13): 3504-9. [PMID:16644217]

3. Faergeman NJ, DiRusso CC, Elberger A, Knudsen J, Black PN. (1997) Disruption of the Saccharomyces cerevisiae homologue to the murine fatty acid transport protein impairs uptake and growth on long-chain fatty acids. J Biol Chem, 272 (13): 8531-8. [PMID:9079682]

4. Gimeno RE, Ortegon AM, Patel S, Punreddy S, Ge P, Sun Y, Lodish HF, Stahl A. (2003) Characterization of a heart-specific fatty acid transport protein. J Biol Chem, 278 (18): 16039-44. [PMID:12556534]

5. Lewis SE, Listenberger LL, Ory DS, Schaffer JE. (2001) Membrane topology of the murine fatty acid transport protein 1. J Biol Chem, 276 (40): 37042-50. [PMID:11470793]

6. Li H, Black PN, Chokshi A, Sandoval-Alvarez A, Vatsyayan R, Sealls W, DiRusso CC. (2008) High-throughput screening for fatty acid uptake inhibitors in humanized yeast identifies atypical antipsychotic drugs that cause dyslipidemias. J Lipid Res, 49 (1): 230-44. [PMID:17928635]

7. Mihalik SJ, Steinberg SJ, Pei Z, Park J, Kim DG, Heinzer AK, Dacremont G, Wanders RJ, Cuebas DA, Smith KD et al.. (2002) Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling. J Biol Chem, 277 (27): 24771-9. [PMID:11980911]

8. Milger K, Herrmann T, Becker C, Gotthardt D, Zickwolf J, Ehehalt R, Watkins PA, Stremmel W, Füllekrug J. (2006) Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4. J Cell Sci, 119 (Pt 22): 4678-88. [PMID:17062637]

9. Ordovás L, Roy R, Zaragoza P, Rodellar C. (2006) Structural and functional characterization of the bovine solute carrier family 27 member 1 (SLC27A1) gene. Cytogenet Genome Res, 115 (2): 115-22. [PMID:17065791]

10. Sandoval A, Chokshi A, Jesch ED, Black PN, Dirusso CC. (2010) Identification and characterization of small compound inhibitors of human FATP2. Biochem Pharmacol, 79 (7): 990-9. [PMID:19913517]

11. Schaffer JE, Lodish HF. (1994) Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell, 79 (3): 427-36. [PMID:7954810]

12. Stahl A, Hirsch DJ, Gimeno RE, Punreddy S, Ge P, Watson N, Patel S, Kotler M, Raimondi A, Tartaglia LA et al.. (1999) Identification of the major intestinal fatty acid transport protein. Mol Cell, 4 (3): 299-308. [PMID:10518211]

13. Zhou W, Madrid P, Fluitt A, Stahl A, Xie XS. (2010) Development and validation of a high-throughput screening assay for human long-chain fatty acid transport proteins 4 and 5. J Biomol Screen, 15 (5): 488-97. [PMID:20448275]

Andreas Stahl Department of Nutritional Sciences and Toxicology University of California Berkeley, CA 94720