Fatty acid–binding protein


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

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 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. 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. These processes include regulation of gene expression, metabolic regulation, and inflammatory response. These signaling functions may be important in certain disease states, such as cancer and metabolic disorders such as obesity and type 2 diabetes. In obesity, for instance, there is often an altered expression of FABPs in adipose tissue, contributing to abnormal lipid metabolism. FABP function is thus a potential therapeutic target for modifying lipid signalling pathways, inflammatory responses, and metabolic regulation in these and related conditions.

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.

Pseudogenes

PseudogeneComment