Fatty acid–binding protein
From Wikipedia, the free encyclopedia
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.[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
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
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] |