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MetaCyc Enzyme: fatty acid synthase

Gene: FASN Accession Number: HS09992 (MetaCyc)

Synonyms: MGC15706, MGC14367, OA-519, FAS

Species: Homo sapiens

Subunit composition of fatty acid synthase = [FASN]2
         fatty acid synthase monomer = FASN

Summary:
The human fatty acid synthase, encoded by the FASN gene, is a large multifunctional protein, whose main function is to catalyze the synthesis of palmitate and other long-chain saturated fatty acids from acetyl-CoA and malonyl-CoA, in the presence of NADPH.

The enzyme is a homodimer [Smith79], with the subunits arranged in a head to tail fashion [Smith85], and each subunit binds one molecule of the prosthetic group 4'-phosphopantetheine.

In addition to an acyl-carrier-protein domain, each subunit contains domains that catalyze 7 different catalytic activities, which are:

(1) EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase

(2) EC 2.3.1.9, [acyl-carrier-protein] S-malonyltransferase

(3) EC 2.3.1.41, 3-oxoacyl-[acyl-carrier-protein] synthase

(4) EC 1.1.1.100, 3-oxoacyl-[acyl-carrier-protein] reductase

(5) EC 4.2.1.59, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase

(6) EC 1.3.1.10, enoyl-[acyl-carrier-protein] reductase

(7) EC 3.1.2.14 , acyl-[acyl-carrier-protein] hydrolase

Since the substrates do not leave the enzyme during the process, but instead are handed from one functional domain to the next, the full process received its own EC number, EC 2.3.1.85, fatty-acid synthase.

The overall reaction is described as:

acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = a long-chain fatty acid + n CO2 + (n+1) coenzyme A + 2n NADP+

In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-α), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-α.

Citations: [Wang02b, Field02, Ming02, Joseph02, Brink02, Ye00, Hsu96, Kuhajda94, Jayakumar94, Semenkovich95, Jayakumar95, Wakil89]

Gene Citations: [Jayakumar95]

Locations: cytosol

Map Position: [77,892 <- 97,794]

Molecular Weight of Polypeptide: 273.4 kD (from nucleotide sequence)

Unification Links: DIP:DIP-33681N , Mint:MINT-1146154 , PhosphoSite:P49327 , PhylomeDB:P49327 , Pride:P49327 , Protein Model Portal:P49327 , SMR:P49327 , String:P49327 , UniProt:P49327

Relationship Links: Entrez-Nucleotide:PART-OF:U26644 , InterPro:IN-FAMILY:IPR001031 , InterPro:IN-FAMILY:IPR001227 , InterPro:IN-FAMILY:IPR002198 , InterPro:IN-FAMILY:IPR006162 , InterPro:IN-FAMILY:IPR009081 , InterPro:IN-FAMILY:IPR011032 , InterPro:IN-FAMILY:IPR013149 , InterPro:IN-FAMILY:IPR013217 , InterPro:IN-FAMILY:IPR014030 , InterPro:IN-FAMILY:IPR014031 , InterPro:IN-FAMILY:IPR014043 , InterPro:IN-FAMILY:IPR016035 , InterPro:IN-FAMILY:IPR016036 , InterPro:IN-FAMILY:IPR016038 , InterPro:IN-FAMILY:IPR016039 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR018201 , InterPro:IN-FAMILY:IPR020842 , InterPro:IN-FAMILY:IPR020843 , InterPro:IN-FAMILY:IPR023102 , Panther:IN-FAMILY:PTHR11712 , PDB:Structure:1XKT , PDB:Structure:2CG5 , PDB:Structure:2JFD , PDB:Structure:2JFK , PDB:Structure:2PX6 , PDB:Structure:3HHD , PDB:Structure:3TJM , Pfam:IN-FAMILY:PF00106 , Pfam:IN-FAMILY:PF00107 , Pfam:IN-FAMILY:PF00109 , Pfam:IN-FAMILY:PF00550 , Pfam:IN-FAMILY:PF00698 , Pfam:IN-FAMILY:PF00975 , Pfam:IN-FAMILY:PF02801 , Pfam:IN-FAMILY:PF08242 , Prosite:IN-FAMILY:PS00012 , Prosite:IN-FAMILY:PS00606 , Prosite:IN-FAMILY:PS50075 , Smart:IN-FAMILY:SM00822 , Smart:IN-FAMILY:SM00829

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005829 - cytosol

Credits:
Created 07-Jul-2008 by Caspi R , SRI International


Enzymatic reaction of: acetoacetyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

an acetyl-[acp] + a malonyl-[acp] + H+ <=> a holo-[acyl-carrier protein] + an acetoacetyl-[acp] + CO2

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: fatty acid biosynthesis initiation II


Enzymatic reaction of: acetyl CoA:ACP transacylase (fatty acid synthase)

EC Number: 2.3.1.85

acetyl-CoA + a holo-[acyl-carrier protein] <=> an acetyl-[acp] + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

This reaction is reversible.

In Pathways: fatty acid biosynthesis initiation II


Enzymatic reaction of: (R)-3-hydroxymyristoyl-[acp] dehydratase (fatty acid synthase)

EC Number: 2.3.1.85

an (3R)-3-hydroxymyristoyl-[acp] <=> a trans tetradec-2-enoyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: (R)-3-hydroxydodecanoyl-[acp] dehydratase (fatty acid synthase)

EC Number: 2.3.1.85

a (R)-3-hydroxydodecanoyl-[acp] <=> a trans dodec-2-enoyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: (R)-3-hydroxydecanoyl-[acp] dehydratase (fatty acid synthase)

EC Number: 2.3.1.85

an (R)-3-hydroxydecanoyl-[acp] <=> a trans2-decenoyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: (R)-3-hydroxyoctanoyl-[acp]dehydratase (fatty acid synthase)

EC Number: 2.3.1.85

a (R)-3-hydroxyoctanoyl-[acp] <=> a trans oct-2-enoyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: (R)-3-hydroxyhexanoyl-[acp] dehydratase (fatty acid synthase)

EC Number: 2.3.1.85

an (R)-3-hydroxyhexanoyl-[acp] <=> a trans hex-2-enoyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: (R)-3-hydroxybutanoyl-[acp] dehydratase (fatty acid synthase)

EC Number: 2.3.1.85

a (R)-3-hydroxybutanoyl-[acp] <=> a crotonyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 3-oxo-palmitoyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

a myristoyl-[acp] + malonyl-CoA + H+ <=> a 3-oxo-palmitoyl-[acp] + CO2 + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 3-oxo-meristoyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

a dodecanoyl-[acp] + malonyl-CoA + H+ <=> a 3-oxo-myristoyl-[acp] + CO2 + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 3-oxo-dodecanoyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

a decanoyl-[acp] + malonyl-CoA + H+ <=> a 3-oxo-dodecanoyl-[acp] + CO2 + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 3-oxo-decanoyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

an octanoyl-[acp] + malonyl-CoA + H+ <=> a 3-oxo-decanoyl-[acp] + CO2 + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 3-oxo-octanoyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

a hexanoyl-[acyl-carrier-protein] + malonyl-CoA + H+ <=> a 3-oxo-octanoyl-[acp] + CO2 + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 3-oxo-hexanoyl-[acp] synthase (fatty acid synthase)

EC Number: 2.3.1.85

a butyryl-[acp] + malonyl-CoA + H+ <=> a 3-oxo-hexanoyl-[acp] + CO2 + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: palmitoyl-[acyl-carrier-protein] hydrolase (fatty acid synthase)

a palmitoyl-[acp] + H2O <=> palmitate + a holo-[acyl-carrier protein] + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: palmitoyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a palmitoyl-[acp] + NADP+ <=> a trans hexadecenoyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: myristoyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a myristoyl-[acp] + NADP+ <=> a trans tetradec-2-enoyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: dodecanoyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a dodecanoyl-[acp] + NADP+ <=> a trans dodec-2-enoyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: decanoyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a decanoyl-[acp] + NADP+ <=> a trans2-decenoyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: octanoyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

an octanoyl-[acp] + NADP+ <=> a trans oct-2-enoyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: hexanoyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a hexanoyl-[acyl-carrier-protein] + NADP+ <=> a trans hex-2-enoyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: crotonyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a butyryl-[acp] + NADP+ <=> a crotonyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: acetoacetyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

an acetoacetyl-[acp] + NADPH + H+ <=> a (R)-3-hydroxybutanoyl-[acp] + NADP+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: acyl-CoA:malonyl-CoA C-acyltransferase (fatty acid synthase)

EC Number: 2.3.1.85

acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ <=> a long-chain fatty acid + n CO2 + (n+1) coenzyme A + 2n NADP+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Cofactors or Prosthetic Groups: 4'-phosphopantetheine [Guy78]


Enzymatic reaction of: malonyl-CoA:[acyl-carrier protein] S-malonyltransferase (fatty acid synthase)

EC Number: 2.3.1.85

a holo-[acyl-carrier protein] + malonyl-CoA <=> a malonyl-[acp] + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

This reaction is reversible.


Enzymatic reaction of: β-ketoacyl-ACP synthase (fatty acid synthase)

EC Number: 2.3.1.85

a 2,3,4-saturated fatty acyl-[acp] + a malonyl-[acp] + H+ <=> a 3-oxoacyl-[acp] + CO2 + a holo-[acyl-carrier protein]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.


Enzymatic reaction of: (3R)-3-hydroxyacyl-[acyl-carrier protein]:NADP+ oxidoreductase (fatty acid synthase)

EC Number: 2.3.1.85

a (3R)-3-hydroxyacyl-[acyl-carrier protein] + NADP+ <=> a 3-oxoacyl-[acp] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.


Enzymatic reaction of: (R)-3-hydroxypalmitoyl-ACP dehydratase (fatty acid synthase)

Synonyms: 3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase

EC Number: 2.3.1.85

an (R)-3-hydroxypalmitoyl-[acp] <=> a trans hexadecenoyl-[acp] + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: palmitate biosynthesis I (animals and fungi)


Enzymatic reaction of: 2,3,4-saturated fatty acyl-[acp] reductase (fatty acid synthase)

EC Number: 2.3.1.85

a 2,3,4-saturated fatty acyl-[acp] + NADP+ <=> a trans-2-enoyl-[acyl-carrier protein] + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

Exons/Introns:


References

Brink02: Brink J, Ludtke SJ, Yang CY, Gu ZW, Wakil SJ, Chiu W (2002). "Quaternary structure of human fatty acid synthase by electron cryomicroscopy." Proc Natl Acad Sci U S A 99(1);138-43. PMID: 11756679

Field02: Field FJ, Born E, Murthy S, Mathur SN (2002). "Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport." Biochem J 368(Pt 3);855-64. PMID: 12213084

Guy78: Guy P, Law S, Hardie G (1978). "Mammalian fatty acid synthetase: evidence for subunit identity and specific removal of the thioesterase component using elastase digestion." FEBS Lett 94(1);33-7. PMID: 700134

Hsu96: Hsu MH, Chirala SS, Wakil SJ (1996). "Human fatty-acid synthase gene. Evidence for the presence of two promoters and their functional interaction." J Biol Chem 271(23);13584-92. PMID: 8662758

Jayakumar94: Jayakumar A, Chirala SS, Chinault AC, Baldini A, Abu-Elheiga L, Wakil SJ (1994). "Isolation and chromosomal mapping of genomic clones encoding the human fatty acid synthase gene." Genomics 23(2);420-4. PMID: 7835891

Jayakumar95: Jayakumar A, Tai MH, Huang WY, al-Feel W, Hsu M, Abu-Elheiga L, Chirala SS, Wakil SJ (1995). "Human fatty acid synthase: properties and molecular cloning." Proc Natl Acad Sci U S A 92(19);8695-9. PMID: 7567999

Joseph02: Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, Collins JL, Osborne TF, Tontonoz P (2002). "Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors." J Biol Chem 277(13);11019-25. PMID: 11790787

Kuhajda94: Kuhajda FP, Jenner K, Wood FD, Hennigar RA, Jacobs LB, Dick JD, Pasternack GR (1994). "Fatty acid synthesis: a potential selective target for antineoplastic therapy." Proc Natl Acad Sci U S A 91(14);6379-83. PMID: 8022791

Ming02: Ming D, Kong Y, Wakil SJ, Brink J, Ma J (2002). "Domain movements in human fatty acid synthase by quantized elastic deformational model." Proc Natl Acad Sci U S A 99(12);7895-9. PMID: 12060737

Semenkovich95: Semenkovich CF, Coleman T, Fiedorek FT (1995). "Human fatty acid synthase mRNA: tissue distribution, genetic mapping, and kinetics of decay after glucose deprivation." J Lipid Res 36(7);1507-21. PMID: 7595075

Smith79: Smith S, Stern A (1979). "Subunit structure of the mammalian fatty acid synthetase: further evidence for a homodimer." Arch Biochem Biophys 197(2);379-87. PMID: 116597

Smith85: Smith S, Stern A, Randhawa ZI, Knudsen J (1985). "Mammalian fatty acid synthetase is a structurally and functionally symmetrical dimer." Eur J Biochem 152(3);547-55. PMID: 3840436

Wakil89: Wakil SJ (1989). "Fatty acid synthase, a proficient multifunctional enzyme." Biochemistry 28(11);4523-30. PMID: 2669958

Wang02b: Wang Y, Zhang X, Tan W, Fu J, Zhang W (2002). "[Significance of fatty acid synthase expression in non-small cell lung cancer]." Zhonghua Zhong Liu Za Zhi 24(3);271-3. PMID: 12515624

Ye00: Ye Q, Chung LW, Li S, Zhau HE (2000). "Identification of a novel FAS/ER-alpha fusion transcript expressed in human cancer cells." Biochim Biophys Acta 1493(3);373-7. PMID: 11018265


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC14B.