Wikipedia

FABP1

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
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFABP1, FABPL, L-FABP, fatty acid binding protein 1
External IDsOMIM: 134650; MGI: 95479; HomoloGene: 1106; GeneCards: FABP1; OMA:FABP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2168

14080

Ensembl

ENSG00000163586

ENSMUSG00000054422

UniProt

P07148

P12710

RefSeq (mRNA)

NM_001443

NM_017399

RefSeq (protein)

NP_001434

NP_059095

Location (UCSC)Chr 2: 88.12 – 88.13 MbChr 6: 71.18 – 71.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

FABP1 is primarily expressed in the liver where it is involved in the binding, transport and metabolism of long-chain fatty acids (LCFAs), endocannabinoids, phytocannabinoids (and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists) and other hydrophobic molecules.[5][6][7][8] Altered expression of the protein has been linked to metabolic conditions including obesity.[9]

Discovery

edit

The fatty acid-binding proteins (FABPs) were initially discovered in 1972 with experiments using 14C labelled oleate to identify the presence of a soluble fatty acid carrier in the enterocyte responsible for intestinal absorption of (LCFAs).[10] 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).[7] Each FABP corresponds to particular organs/tissue around the body where they play a role in fatty-acid uptake, transport and metabolism.[10]

Gene location

edit

The human FABP1 gene is located on the short (p) arm of chromosome 2 from base pair 88,122,982 to base pair 88,128,131.[11]

Protein structure

edit

FABP1 has been found to have a unique structure compared to other members of the FABP family, allowing it to bind multiple ligands simultaneously.[12] It also has a larger solvent-accessible core compared to other FABPs allowing more diverse substrate binding.[7] The “portal hypothesis” has been proposed to explain the binding process of FABPs.[7] 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.[13] The fatty acid is then bound in the protein cavity for transport.[13]

Function

edit

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.[7][14] FABP1 is unique in the wider range of other hydrophobic ligands it can bind including bilirubin, monoglycerides, bile acids and fatty acyl CoA.[15][16][17][18] It has been proposed that FABP1 plays a significant role in preventing cytotoxicity by binding heme, fatty acids and other molecules that are potentially toxic when unbound.[12]

Mutations

edit

A missense mutation within exon 3 of the human FABP1 gene results in a Thr to Ala substitution, T94A, in the protein product.[19] Carriers of this particular single nucleotide polymorphism (SNP) exhibit higher baseline plasma-free fatty acid levels, lower BMI and a smaller waist circumference.[19] The T94A mutant has also been associated with metabolic syndrome conditions, cardiovascular disease and T2DM.[19]

Protein expression

edit

Suppression

edit

Studies with mice to determine the effect of suppressing their Fabp1 gene ortholog 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.[20][21][22][23][24]

Increased levels in obesity

edit

A study in Chinese young adults indicates a strong relationship between serum FABP1 levels and lipid profile, body measurements and homeostatic parameters.[9] Increased BMI and insulin resistance in subjects demonstrated higher serum FABP1 with a particular correlation in subjects with central adiposity.[9] 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.[9]

Disease marker

edit

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.[25][26][27]

References

edit
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163586 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054422 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Schroeder F, McIntosh AL, Martin GG, Huang H, Landrock D, Chung S, Landrock KK, Dangott LJ, Li S, Kaczocha M, Murphy EJ, Atshaves BP, Kier AB (June 2016). "Fatty Acid Binding Protein-1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias". Lipids. 51 (6): 655–76. doi:10.1007/s11745-016-4155-8. PMC 5408584. PMID 27117865.
  6. ^ Huang H, McIntosh AL, Martin GG, Landrock D, Chung S, Landrock KK, Dangott LJ, Li S, Kier AB, Schroeder F (September 2016). "FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein". Biochemistry. 55 (37): 5243–55. doi:10.1021/acs.biochem.6b00446. PMC 5322802. PMID 27552286.
  7. ^ a b c d e Smathers RL, Petersen DR (March 2011). "The human fatty acid-binding protein family: evolutionary divergences and functions". Human Genomics. 5 (3): 170–91. doi:10.1186/1479-7364-5-3-170. PMC 3500171. PMID 21504868.
  8. ^ Huang, Huan; McIntosh, Avery L.; Martin, Gregory G.; Landrock, Danilo; Chung, Sarah; Landrock, Kerstin K.; Dangott, Lawrence J.; Li, Shengrong; Kier, Ann B. (2016-09-20). "FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein". Biochemistry. 55 (37): 5243–5255. doi:10.1021/acs.biochem.6b00446. ISSN 1520-4995. PMC 5322802. PMID 27552286.
  9. ^ a b c d Shi J, Zhang Y, Gu W, Cui B, Xu M, Yan Q, Wang W, Ning G, Hong J (2012-11-07). "Serum liver fatty acid binding protein levels correlate positively with obesity and insulin resistance in Chinese young adults". PLOS ONE. 7 (11): e48777. Bibcode:2012PLoSO...748777S. doi:10.1371/journal.pone.0048777. PMC 3492433. PMID 23144966.
  10. ^ a b Ockner RK (1990). "Historic overview of studies on fatty acid-binding proteins". Molecular and Cellular Biochemistry. 98 (1–2): 3–9. doi:10.1007/bf00231361. PMID 2266967. S2CID 29623496.
  11. ^ "FABP 1". Gene Cards. Retrieved 2016-10-16.
  12. ^ a b Wang G, Bonkovsky HL, de Lemos A, Burczynski FJ (December 2015). "Recent insights into the biological functions of liver fatty acid binding protein 1". Journal of Lipid Research. 56 (12): 2238–47. doi:10.1194/jlr.R056705. PMC 4655993. PMID 26443794.
  13. ^ a b Sacchettini JC, Gordon JI, Banaszak LJ (July 1989). "Crystal structure of rat intestinal fatty-acid-binding protein. Refinement and analysis of the Escherichia coli-derived protein with bound palmitate". Journal of Molecular Biology. 208 (2): 327–39. doi:10.1016/0022-2836(89)90392-6. PMID 2671390.
  14. ^ Vergani L, Fanin M, Martinuzzi A, Galassi A, Appi A, Carrozzo R, Rosa M, Angelini C (1990). "Liver fatty acid-binding protein in two cases of human lipid storage". Molecular and Cellular Biochemistry. 98 (1–2): 225–30. doi:10.1007/bf00231388. PMID 2266963. S2CID 25712825.
  15. ^ Levi AJ, Gatmaitan Z, Arias IM (November 1969). "Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions". Journal of Clinical Investigation. 48 (11): 2156–67. doi:10.1172/jci106182. PMC 297469. PMID 4980931.
  16. ^ Storch J (1993). "Diversity of fatty acid-binding protein structure and function: studies with fluorescent ligands". Molecular and Cellular Biochemistry. 123 (1–2): 45–53. doi:10.1007/BF01076474. PMID 8232268. S2CID 11631346.
  17. ^ Thumser AE, Wilton DC (December 1996). "The binding of cholesterol and bile salts to recombinant rat liver fatty acid-binding protein". Biochemical Journal. 320 (3): 729–33. doi:10.1042/bj3200729. PMC 1217991. PMID 9003356.
  18. ^ Mishkin S, Turcotte R (April 1974). "The binding of long chain fatty acid CoA to Z, a cytoplasmic protein present in liver and other tissues of the rat". Biochemical and Biophysical Research Communications. 57 (3): 918–26. doi:10.1016/0006-291X(74)90633-0. PMID 4827841.
  19. ^ a b c Brouillette C, Bossé Y, Pérusse L, Gaudet D, Vohl MC (2004). "Effect of liver fatty acid binding protein (FABP) T94A missense mutation on plasma lipoprotein responsiveness to treatment with fenofibrate". Journal of Human Genetics. 49 (8): 424–32. doi:10.1007/s10038-004-0171-2. PMID 15249972.
  20. ^ Atshaves BP, Martin GG, Hostetler HA, McIntosh AL, Kier AB, Schroeder F (November 2010). "Liver fatty acid-binding protein and obesity". The Journal of Nutritional Biochemistry. 21 (11): 1015–32. doi:10.1016/j.jnutbio.2010.01.005. PMC 2939181. PMID 20537520.
  21. ^ Martin GG, Atshaves BP, McIntosh AL, Mackie JT, Kier AB, Schroeder F (January 2006). "Liver fatty acid binding protein gene ablation potentiates hepatic cholesterol accumulation in cholesterol-fed female mice". American Journal of Physiology. Gastrointestinal and Liver Physiology. 290 (1): G36-48. doi:10.1152/ajpgi.00510.2004. PMID 16123197.
  22. ^ Atshaves BP, McIntosh AL, Storey SM, Landrock KK, Kier AB, Schroeder F (February 2010). "High dietary fat exacerbates weight gain and obesity in female liver fatty acid binding protein gene-ablated mice". Lipids. 45 (2): 97–110. doi:10.1007/s11745-009-3379-2. PMC 2831749. PMID 20035485.
  23. ^ Newberry EP, Xie Y, Kennedy S, Han X, Buhman KK, Luo J, Gross RW, Davidson NO (December 2003). "Decreased hepatic triglyceride accumulation and altered fatty acid uptake in mice with deletion of the liver fatty acid-binding protein gene". Journal of Biological Chemistry. 278 (51): 51664–72. doi:10.1074/jbc.M309377200. PMID 14534295.
  24. ^ "Fabp1 fatty acid binding protein 1, liver [ Mus musculus (house mouse) ]". Gene. National Library of Medicine, National Center for Biotechnology Information. 9 May 2024. Gene ID #14080. Retrieved 5 August 2024.
  25. ^ Thuijls G, van Wijck K, Grootjans J, Derikx JP, van Bijnen AA, Heineman E, Dejong CH, Buurman WA, Poeze M (February 2011). "Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins". Annals of Surgery. 253 (2): 303–8. doi:10.1097/sla.0b013e318207a767. PMID 21245670. S2CID 206078242.
  26. ^ Obata Y, Kamijo-Ikemori A, Ichikawa D, Sugaya T, Kimura K, Shibagaki Y, Tateda T (February 2016). "Clinical usefulness of urinary liver-type fatty-acid-binding protein as a perioperative marker of acute kidney injury in patients undergoing endovascular or open-abdominal aortic aneurysm repair". Journal of Anesthesia. 30 (1): 89–99. doi:10.1007/s00540-015-2095-8. PMC 4750552. PMID 26585768.
  27. ^ Kamijo A, Sugaya T, Hikawa A, Kimura K (March 2003). "[Urinary fatty acid binding protein as a new clinical marker for the progression of chronic renal disease]". Rinsho Byori. 51 (3): 219–24. doi:10.1016/j.lab.2003.08.001. PMID 12707994.

Further reading

edit
Retrieved from "https://en.wikipedia.org/w/index.php?title=FABP1&oldid=1238763568"