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MetaCyc Enzyme: NADPH-cytochrome P450 reductase

Gene: POR Accession Number: G-10911 (MetaCyc)

Species: Oryctolagus cuniculus

Component of: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase

Summary:
The enzyme is believed to form a stable, 1:1 complex with cytochrome P450 (in [Black82]).

The native apparent molecular mass was determined by SDS-PAGE [Black82].

Gene Citations: [Katagiri86]

Molecular Weight of Polypeptide: 76.588 kD (from nucleotide sequence), 77.0 kD (experimental) [Black82 ]

Unification Links: Protein Model Portal:P00389 , SMR:P00389 , String:9986.ENSOCUP00000020921 , UniProt:P00389

Relationship Links: Entrez-Nucleotide:PART-OF:D00101 , InterPro:IN-FAMILY:IPR001094 , InterPro:IN-FAMILY:IPR001433 , InterPro:IN-FAMILY:IPR001709 , InterPro:IN-FAMILY:IPR003097 , InterPro:IN-FAMILY:IPR008254 , InterPro:IN-FAMILY:IPR017927 , InterPro:IN-FAMILY:IPR017938 , InterPro:IN-FAMILY:IPR023173 , InterPro:IN-FAMILY:IPR023208 , Pfam:IN-FAMILY:PF00175 , Pfam:IN-FAMILY:PF00258 , Pfam:IN-FAMILY:PF00667 , Prints:IN-FAMILY:PR00369 , Prints:IN-FAMILY:PR00371 , Prosite:IN-FAMILY:PS50902 , Prosite:IN-FAMILY:PS51384

Gene-Reaction Schematic: ?

Credits:
Created 15-Oct-2008 by Fulcher CA , SRI International


Enzymatic reaction of: NADPH-cytochrome P450 reductase

EC Number: 1.6.2.4

n oxidized hemoproteins + NADPH + H+ <=> n reduced hemoproteins + 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.

Summary:
Cytochrome b5 is also reduced by this enzyme (in [Black82]).

Cofactors or Prosthetic Groups: FAD [Black82], FMN [Black82]


Subunit of: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase

Synonyms: CYP12

Species: Oryctolagus cuniculus

Subunit composition of 7α-hydroxycholest-4-en-3-one 12α-hydroxylase = [POR][CYP8B1]
         NADPH-cytochrome P450 reductase = POR (summary available)
         cytochrome P450 8B1 = CYP8B1 (summary available)

Credits:
Created 15-Oct-2008 by Fulcher CA , SRI International


Enzymatic reaction of: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase

Synonyms: 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase, sterol 12α-hydroxylase, 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase, 7α-hydroxycholest-4-en-3-one,NADPH:oxygen oxidoreductase (12α-hydroxylating)

EC Number: 1.14.13.95

7α-hydroxycholest-4-en-3-one + NADPH + H+ + oxygen <=> 7α,12α-dihydroxycholest-4-en-3-one + NADP+ + 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 physiologically favored in the direction shown.

In Pathways: bile acid biosynthesis, neutral pathway

Summary:
This enzyme requires NADPH-cytochrome P450 reductase for its activity. It was assayed using the reductase, phospholipid and a NADPH regenerating system. Inclusion of cytochrome b5 enhanced the activity [Ishida92].

The level of this enzyme activity determines the relative amounts of cholate and chenodeoxycholate (or other species-specific bile acid) produced in the liver. The 12α hydroxylation leads to cholate biosynthesis (reviewed in [Russell03] and [Norlin07]).

This enzyme also catalyzes EC 1.14.13.96 (5β-cholestane-3α,7α-diol + NAD(P)H + oxygen + H+ → 5β-cholestane-3α,7α,12α-triol + NAD(P)+ + H2O) and has broad substrate specificity, although 7α-hydroxycholest-4-en-3-one was the more efficient substrate. Recombinant enzyme was also demonstrated to have these activities [Andersson98].


References

Andersson98: Andersson U, Eggertsen G, Bjorkhem I (1998). "Rabbit liver contains one major sterol 12alpha-hydroxylase with broad substrate specificity." Biochim Biophys Acta 1389(2);150-4. PMID: 9461256

Black82: Black SD, Coon MJ (1982). "Structural features of liver microsomal NADPH-cytochrome P-450 reductase. Hydrophobic domain, hydrophilic domain, and connecting region." J Biol Chem 257(10);5929-38. PMID: 6802823

Ishida92: Ishida H, Noshiro M, Okuda K, Coon MJ (1992). "Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase." J Biol Chem 267(30);21319-23. PMID: 1400444

Katagiri86: Katagiri M, Murakami H, Yabusaki Y, Sugiyama T, Okamoto M, Yamano T, Ohkawa H (1986). "Molecular cloning and sequence analysis of full-length cDNA for rabbit liver NADPH-cytochrome P-450 reductase mRNA." J Biochem 100(4);945-54. PMID: 3029050

Norlin07: Norlin M, Wikvall K (2007). "Enzymes in the conversion of cholesterol into bile acids." Curr Mol Med 7(2);199-218. PMID: 17346171

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


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 Nov 24, 2014, biocyc14.