''FABP1'' is a human gene coding for the protein product FABP1 (Fatty Acid-Binding Protein 1). It is also frequently known as liver-type fatty acid-binding protein (LFABP). FABP1 is primarily expressed in the liver where it is involved in the binding, transport and metabolism of

long-chain fatty acids In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

(LCFAs),

endocannabinoids Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

phytocannabinoids Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

(and less so for synthetic

cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cann ...

(CBR)

agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...

and

antagonists An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. Altered expression of the protein has been linked to metabolic conditions including obesity.

Discovery

The

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 and retinoids. These proteins are thought to facilitate the transfer of fatty acids between extra- and i ...

s (FABPs) were initially discovered in 1972 with experiments using ¹⁴C labelled

oleate Oleic acid is a fatty acid that occurs naturally in various animal and vegetable fats and oils. It is an odorless, colorless oil, although commercial samples may be yellowish due to the presence of impurities. In chemical terms, oleic acid is cla ...

to identify the presence of a soluble fatty acid carrier in the enterocyte responsible for intestinal absorption of (LCFAs). Since then, ten members of the FABP family have been identified in the human genome. Nine are well established (FABP1-9) with a recently discovered tenth (FABP12). Each FABP corresponds to particular organs/tissue around the body where they play a role in fatty-acid uptake, transport and metabolism.

Gene location

The human ''FABP1'' gene is located on the short (p) arm of

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost ei ...

from base pair 88,122,982 to base pair 88,128,131.

Protein structure

FABP1 has been found to have a unique structure compared to other members of the FABP family, allowing it to bind multiple ligands simultaneously. It also has a larger solvent-accessible core compared to other FABPs allowing more diverse substrate binding. The “portal hypothesis” has been proposed to explain the binding process of FABPs. It has been suggested that fatty acids enter the solvent-accessible area of the protein through a dynamic region consisting of α-helix II and turns between the βC-βD and βE-βF loops. The fatty acid is then bound in the protein cavity for transport.

Function

The FABPs are a family of small, highly conserved cytoplasmic proteins involved in the binding of LCFAs. FABP1 is expressed abundantly in the human liver where it accounts for 7-11% of the total cytosolic protein, and can also be found in the intestine, kidney, pancreas, stomach and lung. FABP1 is unique in the wider range of other hydrophobic ligands it can bind including

bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...

monoglyceride Monoglycerides (also: acylglycerols or monoacylglycerols) are a class of glycerides which are composed of a molecule of glycerol linked to a fatty acid via an ester bond. As glycerol contains both primary and secondary alcohol groups two differe ...

s, bile acids and fatty

acyl CoA Acyl-CoA is a group of CoA-based coenzymes that metabolize carboxylic acids. Fatty acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents ...

. It has been proposed that FABP1 plays a significant role in preventing cytotoxicity by binding

heme Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...

, fatty acids and other molecules that are potentially toxic when unbound.

Mutations

A missense mutation within exon 3 of the human ''FABP1'' gene results in a Thr to Ala substitution, T94A, in the protein product. Carriers of this particular

single nucleotide polymorphism In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...

(SNP) exhibit higher baseline plasma-free fatty acid levels, lower BMI and a smaller waist circumference. The T94A mutant has also been associated with metabolic syndrome conditions, cardiovascular disease and T2DM.

Protein expression

Suppression

Studies with mice to determine the effect of suppressing their ''Fabp1'' gene

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

have been performed. When provided with high-fat or high-cholesterol based diets those with suppressed FABP1 expression demonstrated a significant impact on metabolic regulation and weight gain.

Increased levels in obesity

A study in Chinese young adults indicates a strong relationship between serum FABP1 levels and lipid profile, body measurements and homeostatic parameters. Increased BMI and insulin resistance in subjects demonstrated higher serum FABP1 with a particular correlation in subjects with central adiposity. This elevation is suggested to occur as a compensatory up-regulation of the protein in an attempt to counter the high metabolic stress associated with obesity. Alternately obesity may in fact lead the human body to develop resistance to the actions of FABP1 leading to the compensatory up-regulation.

Disease marker

Evaluation of increased levels of urinary and serum FABP1 have also shown to be effective markers in the detection of intestinal ischaemia, progressive end-stage renal failure and ischaemic damage caused by renal transplantation or cardiac bypass surgery.