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MetaCyc Enzyme: peroxisomal acyl-coenzyme A oxidase 2

Gene: Acox2 Accession Number: G-10922 (MetaCyc)

Synonyms: Thcox

Species: Rattus norvegicus

Subunit composition of peroxisomal acyl-coenzyme A oxidase 2 = [Acox2]2
         (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA dehydrogenase subunit = Acox2

Summary:
The native apparent molecular mass was determined by gel filtration chromatography [Van94].

The native enzyme has been purified from rat liver [Van94].

Three acyl-coenzyme A oxidase isozymes with different substrate specificities have been described in rat liver peroxisomes [Schepers90, Ikegawa98], whereas two isozymes have been described in humans [Baumgart96].

Recombinant rabbit liver enzyme has been expressed and its activity demonstrated [Pedersen97a].
The subunit apparent molecular mass was determined by SDS-PAGE [Van94].

Gene Citations: [Baumgart96a]

Locations: peroxisome

Map Position: [18,645,349 -> 18,677,855]

Molecular Weight of Polypeptide: 68.6 kD (experimental) [Van94 ]

Molecular Weight of Multimer: 120.0 kD (experimental) [Van94]

Unification Links: Entrez-gene:252898 , PhosphoSite:P97562 , Pride:P97562 , Protein Model Portal:P97562 , String:10116.ENSRNOP00000010260 , UniProt:P97562

Relationship Links: InterPro:IN-FAMILY:IPR002655 , InterPro:IN-FAMILY:IPR006091 , InterPro:IN-FAMILY:IPR009075 , InterPro:IN-FAMILY:IPR009100 , InterPro:IN-FAMILY:IPR012258 , InterPro:IN-FAMILY:IPR013786 , Panther:IN-FAMILY:PTHR10909:SF11 , Pfam:IN-FAMILY:PF01756 , Pfam:IN-FAMILY:PF02770

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005777 - peroxisome [Van94]

Credits:
Created 23-Oct-2008 by Fulcher CA , SRI International


Enzymatic reaction of: (25S)-3α,7α-dihydroxy-5β-cholestanoyl-CoA dehydrogenase (peroxisomal acyl-coenzyme A oxidase 2)

(25S)-3α,7α-dihydroxy-5β-cholestanoyl-CoA + an oxidized electron acceptor <=> (24E)-3α,7α-dihydroxy-5β-cholest-24-enoyl-CoA + a reduced electron acceptor

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: bile acid biosynthesis, neutral pathway


Enzymatic reaction of: (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA dehydrogenase (peroxisomal acyl-coenzyme A oxidase 2)

Synonyms: THCA-CoA oxidase, 3α,7α,12α-trihydroxy-5-beta-cholestanoyl-CoA oxidase, trihydroxycoprostanoyl-CoA oxidase, trihydroxycholestanoyl-CoA oxidase

EC Number: 1.17.99.-

(25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA + an oxidized electron acceptor <=> (24E)-3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA + a reduced electron acceptor

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: bile acid biosynthesis, neutral pathway

Summary:
This enzyme catalyzes dehydrogenation of (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA, which has an asymetric center at C-25, to produce (24E)-3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA [Ikegawa98]. It prefers the S-isomer of this substrate [Ikegawa98, Van96a]. It is the first step of peroxisomal β-oxidation of the side chain of (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA, an intermediate in bile acid biosynthesis (in [Ikegawa98]).

The mechanism of this reaction and any participating cofactors have not been described.

The enzyme also uses 2-methyl-branched fatty acyl-CoA esters as substrates. The presence of albumin in the assay mixture was required for assay [Van94].

Although this enzyme has been associated with EC 1.17.99.3, the EC comments for EC 1.17.99.3 suggested a mammalian hydroxylase enzyme reaction that involves dehydrogenation followed by hydration. They also described an amphibian enzyme reaction that involves direct hydroxylation. However, in mammalian liver peroxisomes, dehydrogenation of (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA to (24E)-3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA is accomplished by the peroxisomal oxidase described here (or its ortholog in other species), whereas hydration of (24E)-3α,7α,12α-trihydroxy-5β-cholest-24-enoyl-CoA to (24R,25R)-3α,7α,12α,24-tetrahydroxy-5β-cholestanoyl CoA and its subsequent dehydrogenation to 3α,7α,12α-trihydroxy-24-oxo-5-β-cholestanoyl CoA are catalyzed by a different peroxisomal gene product, D-bifunctional protein (in [Russell03, Ferdinandusse05, Cuebas02]). Therefore, EC 1.17.99.3 was not used here.

Cofactors or Prosthetic Groups: FAD [Van94]


References

Baumgart96: Baumgart E, Vanhooren JC, Fransen M, Marynen P, Puype M, Vandekerckhove J, Leunissen JA, Fahimi HD, Mannaerts GP, van Veldhoven PP (1996). "Molecular characterization of the human peroxisomal branched-chain acyl-CoA oxidase: cDNA cloning, chromosomal assignment, tissue distribution, and evidence for the absence of the protein in Zellweger syndrome." Proc Natl Acad Sci U S A 93(24);13748-53. PMID: 8943006

Baumgart96a: Baumgart E, Vanhooren JC, Fransen M, Van Leuven F, Fahimi HD, Van Veldhoven PP, Mannaerts GP (1996). "Molecular cloning and further characterization of rat peroxisomal trihydroxycoprostanoyl-CoA oxidase." Biochem J 320 ( Pt 1);115-21. PMID: 8947475

Cuebas02: Cuebas DA, Phillips C, Schmitz W, Conzelmann E, Novikov DK (2002). "The role of alpha-methylacyl-CoA racemase in bile acid synthesis." Biochem J 363(Pt 3);801-7. PMID: 11964182

Ferdinandusse05: Ferdinandusse S, Denis S, Overmars H, Van Eeckhoudt L, Van Veldhoven PP, Duran M, Wanders RJ, Baes M (2005). "Developmental changes of bile acid composition and conjugation in L- and D-bifunctional protein single and double knockout mice." J Biol Chem 280(19);18658-66. PMID: 15769750

Ikegawa98: Ikegawa S, Goto T, Mano N, Goto J (1998). "Substrate specificity of THCA-CoA oxidases from rat liver light mitochondrial fractions on dehydrogenation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid CoA thioester." Steroids 63(11);603-7. PMID: 9830687

Pedersen97a: Pedersen JI, Eggertsen G, Hellman U, Andersson U, Bjorkhem I (1997). "Molecular cloning and expression of cDNA encoding 3alpha,7alpha,12alpha-trihydroxy-5beta-chole stanoyl-CoA oxidase from rabbit liver." J Biol Chem 272(29);18481-9. PMID: 9218493

Prydz86: Prydz K, Kase BF, Bjorkhem I, Pedersen JI (1986). "Formation of chenodeoxycholic acid from 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid by rat liver peroxisomes." J Lipid Res 27(6);622-8. PMID: 3746130

Russell03: Russell DW (2003). "The enzymes, regulation, and genetics of bile acid synthesis." Annu Rev Biochem 72;137-74. PMID: 12543708

Schepers90: Schepers L, Van Veldhoven PP, Casteels M, Eyssen HJ, Mannaerts GP (1990). "Presence of three acyl-CoA oxidases in rat liver peroxisomes. An inducible fatty acyl-CoA oxidase, a noninducible fatty acyl-CoA oxidase, and a noninducible trihydroxycoprostanoyl-CoA oxidase." J Biol Chem 265(9);5242-6. PMID: 2156865

Van94: Van Veldhoven PP, Van Rompuy P, Vanhooren JC, Mannaerts GP (1994). "Purification and further characterization of peroxisomal trihydroxycoprostanoyl-CoA oxidase from rat liver." Biochem J 304 ( Pt 1);195-200. PMID: 7998933

Van96a: Van Veldhoven PP, Croes K, Asselberghs S, Herdewijn P, Mannaerts GP (1996). "Peroxisomal beta-oxidation of 2-methyl-branched acyl-CoA esters: stereospecific recognition of the 2S-methyl compounds by trihydroxycoprostanoyl-CoA oxidase and pristanoyl-CoA oxidase." FEBS Lett 388(1);80-4. PMID: 8654595


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 Sat Dec 20, 2014, biocyc12.