Adrenodoxin reductase
| Ferredoxin reductase | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbols | FDXR ; ADXR | ||||||||||||
| External IDs | OMIM: 103270 MGI: 104724 HomoloGene: 3033 GeneCards: FDXR Gene | ||||||||||||
| EC number | 1.18.1.6 | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| More reference expression data | |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 2232 | 14149 | |||||||||||
| Ensembl | ENSG00000161513 | ENSMUSG00000018861 | |||||||||||
| UniProt | P22570 | Q61578 | |||||||||||
| RefSeq (mRNA) | NM_001258012 | NM_007997 | |||||||||||
| RefSeq (protein) | NP_001244941 | NP_032023 | |||||||||||
| Location (UCSC) | Chr 17: 72.86 – 72.87 Mb | Chr 11: 115.27 – 115.28 Mb | |||||||||||
| PubMed search | |||||||||||||
NADPH:adrenodoxin oxidoreductase, mitochondrial also known as adrenodoxin reductase is an enzyme that in humans is encoded by the FDXR gene, also known as ADXR. It catalyzes the following reaction:
- NADPH + 2 oxidized adrenodoxin —→ 2 reduced adrenodoxin + NADP+ + H+
In both bovine and human genomes there is only a single copy of this gene.[1]
ADXR gene is expressed in all tissues that have mitochondrial P450s. The highest levels of the enzyme is found in the adrenal cortex, granulosa cells of the ovary and leydig cells of the testis that specialize in steroid hormone synthesis.[2] In addition the enzyme is also expressed in the liver, the kidney and the placenta.
Function
Adrenodoxin reductase is a mitochondrial flavoprotein as it carries a FAD type coenzyme. The enzyme functions as the first electron transfer protein of mitochondrial P450 systems such as P450scc. The FAD coenzyme receives two electrons from NADPH and transfers them one at a time to the electron transfer protein adrenodoxin.[3] Adrenodoxin functions as a mobile shuttle that transfers electrons between ADXR and mitochondrial P450s.[4]
Adrenodoxin reductase has been also called a ferredoxin-NADP+ reductase. But, determination of the sequence and structure of the enzyme revealed that it is completely different from ferredoxin reductase.[5][6]
References
- ↑ Hanukoglu, I.; Gutfinger, T.; Haniu, M.; Shively, JE. (Dec 1987). "Isolation of a cDNA for adrenodoxin reductase (ferredoxin-NADP+ reductase). Implications for mitochondrial cytochrome P-450 systems.". Eur J Biochem 169 (3): 449–55. doi:10.1111/j.1432-1033.1987.tb13632.x. PMID 3691502.
- ↑ Hanukoglu I, Hanukoglu Z (May 1986). "Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation.". Eur J Biochem 157 (1): 27–31. doi:10.1111/j.1432-1033.1986.tb09633.x. PMID 3011431.
- ↑ Lambeth JD, Kamin H (July 1976). "Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH". J. Biol. Chem. 251 (14): 4299–306. PMID 6475.
- ↑ Hanukoglu I, Jefcoate CR (Apr 1980). "Mitochondrial cytochrome P-450sec. Mechanism of electron transport by adrenodoxin." (PDF). J Biol Chem 255 (7): 3057–61. PMID 6766943.
- ↑ Hanukoglu I, Gutfinger T (March 1989). "cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases". Eur. J. Biochem. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
- ↑ Ziegler GA, Vonrhein C, Hanukoglu I, Schulz GE (June 1999). "The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis". J. Mol. Biol. 289 (4): 981–90. doi:10.1006/jmbi.1999.2807. PMID 10369776.
Further reading
- Sparkes RS, Klisak I, Miller WL (1991). "Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25". DNA Cell Biol. 10 (5): 359–65. doi:10.1089/dna.1991.10.359. PMID 1863359.
- Coghlan VM, Vickery LE (1991). "Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc". J. Biol. Chem. 266 (28): 18606–12. PMID 1917982.
- Lin D, Shi YF, Miller WL (1990). "Cloning and sequence of the human adrenodoxin reductase gene". Proc. Natl. Acad. Sci. U.S.A. 87 (21): 8516–20. doi:10.1073/pnas.87.21.8516. PMC 54987. PMID 2236061.
- Usanov SA, Chernogolov AA, Honkakoski P et al. (1990). "[Cholesterol-hydroxylating cytochrome P-450 from bovine adrenal cortex mitochondria and human placenta: immunochemical properties and structural characteristics]". Biokhimiia 55 (5): 865–77. PMID 2393675.
- Sasano H, Sasano N, Okamoto M, Nonaka Y (1989). "Immunohistochemical demonstration of adrenodoxin reductase in bovine and human adrenals". Pathol. Res. Pract. 184 (5): 473–9. doi:10.1016/s0344-0338(89)80137-2. PMID 2748461.
- Usanov SA, Honkakoski P, Lang MA et al. (1989). "Comparison of the immunochemical properties of human placental and bovine adrenal cholesterol side-chain cleavage enzyme complex". Biochim. Biophys. Acta 998 (2): 189–95. doi:10.1016/0167-4838(89)90272-0. PMID 2790061.
- Solish SB, Picado-Leonard J, Morel Y et al. (1988). "Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues". Proc. Natl. Acad. Sci. U.S.A. 85 (19): 7104–8. doi:10.1073/pnas.85.19.7104. PMC 282132. PMID 2845396.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Müller JJ, Lapko A, Bourenkov G et al. (2001). "Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis". J. Biol. Chem. 276 (4): 2786–9. doi:10.1074/jbc.M008501200. PMID 11053423.
- Gonzalez MI, Robins DM (2001). "Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that facilitates recruitment of SRC-1". J. Biol. Chem. 276 (9): 6420–8. doi:10.1074/jbc.M008689200. PMID 11096094.
- Tuckey RC, Headlam MJ (2002). "Placental cytochrome P450scc (CYP11A1): comparison of catalytic properties between conditions of limiting and saturating adrenodoxin reductase". J. Steroid Biochem. Mol. Biol. 81 (2): 153–8. doi:10.1016/S0960-0760(02)00058-4. PMID 12137805.
- Liu G, Chen X (2002). "The ferredoxin reductase gene is regulated by the p53 family and sensitizes cells to oxidative stress-induced apoptosis". Oncogene 21 (47): 7195–204. doi:10.1038/sj.onc.1205862. PMID 12370809.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Araya Z, Hosseinpour F, Bodin K, Wikvall K (2003). "Metabolism of 25-hydroxyvitamin D3 by microsomal and mitochondrial vitamin D3 25-hydroxylases (CYP2D25 and CYP27A1): a novel reaction by CYP27A1". Biochim. Biophys. Acta 1632 (1–3): 40–7. doi:10.1016/S1388-1981(03)00062-3. PMID 12782149.
- Thiboutot D, Jabara S, McAllister JM et al. (2003). "Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1)". J. Invest. Dermatol. 120 (6): 905–14. doi:10.1046/j.1523-1747.2003.12244.x. PMID 12787114.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Kimura K, Wakamatsu A, Suzuki Y et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.