Fatty acid–binding protein
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
[edit]FABPs share only moderate sequence homology, but have "virtually superimposable" tertiary structures.[3] 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.[3]
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.[3]
Function and clinical significance
[edit]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.[6]
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[7] 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
[edit] |
Members of the FABP gene family include:
| Protein name | Gene | Tissue distribution | Comment |
|---|---|---|---|
| FABP 1 | FABP1 | liver | |
| FABP 2 | FABP2 | intestinal | |
| FABP 3 | FABP3 | muscle and heart | mammary-derived growth inhibitor |
| FABP 4 | FABP4 | adipocyte | |
| FABP 5 | FABP5 | epidermal | psoriasis-associated |
| FABP 6 | FABP6 | ileal | gastrotropin |
| FABP 7 | FABP7 | brain | |
| FABP 8 | PMP2 | peripheral nervous system | peripheral myelin protein 2 |
| FABP 9 | FABP9 | ||
| FABP 11 | fabp11 | restricted to fishes | |
| FABP 12 | FABP12 | presence shown in human retinoblastoma cell lines, rodent retina and testis.[12] |
Pseudogenes
[edit]| Pseudogene | Comment |
|---|---|
| FABP3P2 | |
| FABP5P1 | |
| FABP5P2 | |
| FABP5P3 | |
| FABP5P4 | |
| FABP5P5 | |
| FABP5P6 | |
| FABP5P7 | |
| FABP5P8 | |
| FABP5P9 | |
| FABP5P10 | |
| FABP5P11 | |
| FABP5P12 | |
| FABP5P13 | |
| FABP5P14 | |
| FABP5P15 | |
| FABP7P1 | |
| FABP7P2 | |
| FABP12P1 |
References
[edit]- ↑ Chmurzyńska A (2006). "The multigene family of fatty acid–binding proteins (FABPs): function, structure and polymorphism". Journal of Applied Genetics. 47 (1): 39–48. doi:10.1007/BF03194597. PMID 16424607. S2CID 2622822.
- ↑ Elmes MW, Kaczocha M, Berger WT, Leung K, Ralph BP, Wang L, et al. (April 2015). "Fatty acid–binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)". The Journal of Biological Chemistry. 290 (14): 8711–8721. doi:10.1074/jbc.M114.618447. PMC 4423662. PMID 25666611.
- 1 2 3 4 Smathers RL, Petersen DR (March 2011). "The human fatty acid–binding protein family: evolutionary divergences and functions". Human Genomics. 5 (3): 170–191. doi:10.1186/1479-7364-5-3-170. PMC 3500171. PMID 21504868.
- ↑ Weisiger RA (October 2002). "Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands". Molecular and Cellular Biochemistry. 239 (1–2): 35–43. doi:10.1023/A:1020550405578. PMID 12479566. S2CID 9608133.
- ↑ Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, et al. (July 2002). "Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription". Molecular and Cellular Biology. 22 (14): 5114–5127. doi:10.1128/MCB.22.14.5114-5127.2002. PMC 139777. PMID 12077340.
- 1 2 Storch J, Thumser AE (October 2010). "Tissue-specific functions in the fatty acid–binding protein family". The Journal of Biological Chemistry. 285 (43): 32679–32683. doi:10.1074/jbc.R110.135210. PMC 2963392. PMID 20716527.
- 1 2 Koundouros N, Poulogiannis G (January 2020). "Reprogramming of fatty acid metabolism in cancer". British Journal of Cancer. 122 (1): 4–22. doi:10.1038/s41416-019-0650-z. PMC 6964678. PMID 31819192.
- ↑ Hotamisligil GS (December 2006). "Inflammation and metabolic disorders". Nature. 444 (7121): 860–867. Bibcode:2006Natur.444..860H. doi:10.1038/nature05485. PMID 17167474.
- ↑ Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M, Uysal KT, et al. (February 2005). "Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes". Cell Metabolism. 1 (2): 107–119. doi:10.1016/j.cmet.2004.12.008. PMID 16054052.
- ↑ Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW (December 2003). "Obesity is associated with macrophage accumulation in adipose tissue". The Journal of Clinical Investigation. 112 (12): 1796–1808. doi:10.1172/JCI19246. PMC 296995. PMID 14679176.
- ↑ Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, et al. (June 2007). "Treatment of diabetes and atherosclerosis by inhibiting fatty-acid–binding protein aP2". Nature. 447 (7147): 959–965. Bibcode:2007Natur.447..959F. doi:10.1038/nature05844. PMC 4076119. PMID 17554340.
- ↑ Liu RZ, Li X, Godbout R (December 2008). "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. doi:10.1016/j.ygeno.2008.08.003. PMID 18786628.
External links
[edit]- Fatty+Acid-Binding+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)