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MetaCyc Enzyme: bile acid CoA ligase

Gene: Slc27a5 Accession Number: G-10920 (MetaCyc)

Synonyms: Acsb, Fatp5, Vlacsr, very long-chain acyl-CoA synthetase-related protein, fatty acid transport protein 5, solute carrier family 27 member 5

Species: Rattus norvegicus

Summary:
The rat liver enzyme was purified from rat liver microsomes. The apparent molecular mass was determined by SDS-PAGE. Gel filtratin chromatography suggested that the enzyme forms an aggregate with other proteins [Wheeler97]. The enzyme has been localized to the endoplasmic reticulum membrane [Schepers89, Prydz88].

Active, recombinant, His-tagged enzyme was expressed in Sf9 insect cells [Falany02].

Locations: endoplasmic reticulum membrane

Map Position: [72,924,630 -> 72,935,223]

Molecular Weight of Polypeptide: 76.266 kD (from nucleotide sequence), 65.0 kD (experimental) [Wheeler97 ]

Unification Links: Entrez-gene:79111 , Mint:MINT-4569701 , Pride:Q9ES38 , Protein Model Portal:Q9ES38 , String:10116.ENSRNOP00000026574 , UniProt:Q9ES38

Relationship Links: InterPro:IN-FAMILY:IPR000873 , InterPro:IN-FAMILY:IPR020845 , InterPro:IN-FAMILY:IPR025110 , Pfam:IN-FAMILY:PF00501 , Pfam:IN-FAMILY:PF13193 , Prosite:IN-FAMILY:PS00455

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005789 - endoplasmic reticulum membrane [Schepers89]

Credits:
Created 21-Oct-2008 by Fulcher CA , SRI International


Enzymatic reaction of: (25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA ligase (bile acid CoA ligase)

EC Number: 6.2.1.28

ATP + (25R)-3α,7α-dihydroxy-5-β-cholestanate + coenzyme A <=> AMP + (25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA + diphosphate

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: bile acid biosynthesis, neutral pathway

Summary:
EC 6.2.1.28 appears to be the same enzyme as EC 6.2.1.7, using both dihydroxy and trihydroxy substrates [Wheeler97].


Enzymatic reaction of: (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA ligase (bile acid CoA ligase)

Synonyms: bile acyl-CoA synthetase, 3α,7α,12α-trihydroxy-5β-cholestanoate-CoA ligase, bile acid coenzyme A ligase, 3α,7α,12α-trihydroxy-5β-cholestanoyl-coenzyme A ligase, trihydroxycoprostanoyl-CoA synthetase, cholate-CoA ligase, choloyl-CoA synthetase, cholate:CoA ligase (AMP-forming), choloyl coenzyme A synthetase, cholic thiokinase, cholate thiokinase, cholic acid:CoA ligase, THCA-CoA ligase, cholyl-CoA synthetase, 3α,7α,12α-trihydroxy-5β-cholestanoyl coenzyme A synthetase, 3α,7α,12α-trihydroxy-5β-cholestanoate-CoA synthetase, 3α,7α,12α-trihydroxy-5β-cholestanate, 3α,7α,12α-trihydroxy-5β-cholestanate:CoA ligase (AMP-forming)

(25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + ATP + coenzyme A <=> (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA + AMP + diphosphate

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.

Alternative Substrates for (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate: chenodeoxycholate [Wheeler97 ]

In Pathways: bile acid biosynthesis, neutral pathway

Summary:
This enzyme converts bile acids to their CoA thioesters. When the purified, native enzyme from rat liver was assayed using chenodeoxycholate as a substrate, a pH optimum of 8.5 was determined. The Km values for chenodeoxycholate and ATP were 548 and 18 μM, respectively [Wheeler97].

In studies of the recombinant enzyme expressed in Sf9 cells, norcholate did not inhibit in a dose-dependent manner. The unsaturated fatty acids myristate, palmitate and stearate did not inhibit [Falany02].

Cofactors or Prosthetic Groups: Mg2+ [Wheeler97]

Inhibitors (Unknown Mechanism): palmitoleate [Falany02] , oleate [Falany02] , 3,7,12-trihydroxycoprostanate [Falany02] , cholate [Wheeler97, Falany02] , deoxycholate [Wheeler97, Falany02] , lithocholate [Wheeler97, Falany02]


References

Falany02: Falany CN, Xie X, Wheeler JB, Wang J, Smith M, He D, Barnes S (2002). "Molecular cloning and expression of rat liver bile acid CoA ligase." J Lipid Res 43(12);2062-71. PMID: 12454267

Prydz88: Prydz K, Kase BF, Bjorkhem I, Pedersen JI (1988). "Subcellular localization of 3 alpha, 7 alpha-dihydroxy- and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-coenzyme A ligase(s) in rat liver." J Lipid Res 29(8);997-1004. PMID: 3183523

Schepers89: Schepers L, Casteels M, Verheyden K, Parmentier G, Asselberghs S, Eyssen HJ, Mannaerts GP (1989). "Subcellular distribution and characteristics of trihydroxycoprostanoyl-CoA synthetase in rat liver." Biochem J 257(1);221-9. PMID: 2521999

Wheeler97: Wheeler JB, Shaw DR, Barnes S (1997). "Purification and characterization of a rat liver bile acid coenzyme A ligase from rat liver microsomes." Arch Biochem Biophys 348(1);15-24. PMID: 9390170


Report Errors or Provide Feedback
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 Mon Dec 22, 2014, biocyc14.