''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, particularly 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, fr ...

(LCFAs),

endocannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

phytocannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

(and less so for synthetic

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

(CBR)

agonists An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an ...

and

antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

) and other hydrophobic molecules. 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 ...

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. In chemical terms, oleic acid is classified as a monounsaturated omega ...

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 on 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 e ...

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 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) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

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 differen ...

s, bile acids and fatty

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

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

heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consisti ...

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

Mutations

On exon 3 of the human FABP1 gene an Thr to Ala substitution has been identified leading to a T94A missense mutation. Carriers of this particular

single nucleotide polymorphism In genetics, 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 a sufficiently larg ...

(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 the FABP1 gene 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.