Fatty acid–binding protein explained

The fatty-acid-binding proteins (FABPs) are a family of transport proteins for fatty acids and other lipophilic substances such as eicosanoids, cannabinoids, and retinoids.[1] [2] [3] These proteins are thought to facilitate the transfer of fatty acids between extra- and intracellular membranes.[4] Some family members are also believed to transport lipophilic molecules from outer cell membrane to certain intracellular receptors such as PPAR.[5]

Structure

FABPs share only moderate sequence homology, but have "virtually superimposable" tertiary structures. The proteins contain ten anti-parallel beta sheets, partly covered by a helix-turn-helix motif that regulates transfer of hydrophobic molecules from membranes. The beta-sheets enclose a water-accessible binding pocket. FABPs have broad specificity, including the ability to bind long-chain (C16-C20) fatty acids, eicosanoids, bile salts and peroxisome proliferators; more hydrophobic molecules tend to bind with higher affinity.

FABPs demonstrate strong evolutionary conservation and are present in species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied than the other variants.

Function and clinical significance

As fatty acids are insoluble in water, the primary function of FABPs is to enhance solubility by providing a hydrophilic binding partner for the fatty acid. This solubilization greatly increases the rate of movement of fatty acids between different membranes and cellular compartments, and their delivery to metabolic enzymes.[6] FABPs may also have tissue-specific functions that reflect differences in lipid and fatty acid metabolism. Tissue-specific roles of FABPs include uptake of dietary lipids in the intestine, regulation of lipid storage and lipid-mediated gene expression in adipose tissue and macrophages, and maintenance of phospholipid membranes in neural tissues.

FABPs are also involved in cellular processes unrelated to direct fatty acid use, such as cell signaling in lipid-dependent signaling and metabolic regulation.[7] These processes include regulation of gene expression, metabolic regulation, and inflammatory response.[8] These signaling functions may be important in certain disease states, such as cancer and metabolic disorders such as obesity and type 2 diabetes.[9] In obesity, for instance, there is often an altered expression of FABPs in adipose tissue, contributing to abnormal lipid metabolism.[10] FABP function is thus a potential therapeutic target for modifying lipid signalling pathways, inflammatory responses, and metabolic regulation in these and related conditions.[11]

Family members

Members of the FABP gene family include:

Protein nameGeneTissue distributionComment
FABP 1liver
FABP 2intestinal
FABP 3muscle and heartmammary-derived growth inhibitor
FABP 4adipocyte
FABP 5epidermalpsoriasis-associated
FABP 6ilealgastrotropin
FABP 7brain
FABP 8peripheral nervous systemperipheral myelin protein 2
FABP 9
FABP 11fabp11restricted to fishes
FABP 12presence shown in human retinoblastoma cell lines, rodent retina and testis.[12]

Pseudogenes

See also: Pseudogene.

Notes and References

  1. Chmurzyńska A . The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism . Journal of Applied Genetics . 47 . 1 . 39–48 . 2006 . 16424607 . 10.1007/BF03194597 . 2622822 .
  2. Elmes MW, Kaczocha M, Berger WT, Leung K, Ralph BP, Wang L, Sweeney JM, Miyauchi JT, Tsirka SE, Ojima I, Deutsch DG . 6 . Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) . The Journal of Biological Chemistry . 290 . 14 . 8711–8721 . April 2015 . 25666611 . 4423662 . 10.1074/jbc.M114.618447 . free .
  3. Smathers RL, Petersen DR . The human fatty acid-binding protein family: evolutionary divergences and functions . Human Genomics . 5 . 3 . 170–191 . March 2011 . 21504868 . 3500171 . 10.1186/1479-7364-5-3-170 . free .
  4. Weisiger RA . Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands . Molecular and Cellular Biochemistry . 239 . 1–2 . 35–43 . October 2002 . 12479566 . 10.1023/A:1020550405578 . 9608133 .
  5. Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N . 6 . Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription . Molecular and Cellular Biology . 22 . 14 . 5114–5127 . July 2002 . 12077340 . 139777 . 10.1128/MCB.22.14.5114-5127.2002 .
  6. Storch J, Thumser AE . Tissue-specific functions in the fatty acid-binding protein family . The Journal of Biological Chemistry . 285 . 43 . 32679–32683 . October 2010 . 20716527 . 2963392 . 10.1074/jbc.R110.135210 . free .
  7. Koundouros N, Poulogiannis G . Reprogramming of fatty acid metabolism in cancer . British Journal of Cancer . 122 . 1 . 4–22 . January 2020 . 31819192 . 6964678 . 10.1038/s41416-019-0650-z .
  8. Hotamisligil GS . Inflammation and metabolic disorders . Nature . 444 . 7121 . 860–867 . December 2006 . 17167474 . 10.1038/nature05485 . 2006Natur.444..860H .
  9. Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M, Uysal KT, Cao Q, Atsumi G, Malone H, Krishnan B, Minokoshi Y, Kahn BB, Parker RA, Hotamisligil GS . 6 . Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes . Cell Metabolism . 1 . 2 . 107–119 . February 2005 . 16054052 . 10.1016/j.cmet.2004.12.008 . free .
  10. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW . Obesity is associated with macrophage accumulation in adipose tissue . The Journal of Clinical Investigation . 112 . 12 . 1796–1808 . December 2003 . 14679176 . 10.1172/JCI19246 . free . 296995 .
  11. Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS . 6 . Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2 . Nature . 447 . 7147 . 959–965 . June 2007 . 17554340 . 4076119 . 10.1038/nature05844 . 2007Natur.447..959F .
  12. Liu RZ, Li X, Godbout R . A novel fatty acid-binding protein (FABP) gene resulting from tandem gene duplication in mammals: transcription in rat retina and testis . Genomics . 92 . 6 . 436–445 . December 2008 . 18786628 . 10.1016/j.ygeno.2008.08.003 .

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