Adrenodoxin and Adrenodoxin reductase

Adrenal ferredoxin (also adrenodoxin (ADX), adrenodoxin, mitochondrial, hepatoredoxin, ferredoxin-1 (FDX1)) is a protein that in humans is encoded by the FDX1 gene.

• Mittal S, Zhu YZ, Vickery LE (Sep 1988). “Molecular cloning and sequence analysis of human placental ferredoxin”. Arch Biochem Biophys. 264 (2): 383–91. doi:10.1016/0003-9861(88)90303-7. PMID 2969697.
• “Entrez Gene: FDX1 ferredoxin 1”.

In addition to the expressed gene at this chromosomal locus (11q22), there are pseudogenes located on chromosomes 20 and 21.

Function

Adrenodoxin is a small iron-sulfur protein that can accept and carry a single electron. Adrenodoxin functions as an electron transfer protein in the mitochondrial cytochrome P450 systems.

• Hanukoglu I, Jefcoate CR (Apr 1980). “Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin” (PDF). The Journal of Biological Chemistry. 255 (7): 3057–61. doi:10.1016/S0021-9258(19)85851-9. PMID 6766943.

The first enzyme in this system is adrenodoxin reductase that carries an FAD. FAD can be reduced by two electrons donated from coenzyme NADPH.

• Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.

These two electrons are transferred one a time to adrenodoxin. Adrenodoxin in return reduces mitochondrial cytochrome P450.

• Hanukoglu I, Jefcoate CR (Apr 1980). “Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin” (PDF). The Journal of Biological Chemistry. 255 (7): 3057–61. doi:10.1016/S0021-9258(19)85851-9. PMID 6766943.

This particular oxidation/reduction system is involved in the synthesis of steroid hormones in steroidogenic tissues. In addition, similar systems also function in vitamin D and bile acid synthesis in the kidney and liver respectively. Adrenodoxin has been identified in a number of different tissues but all forms have been shown to be identical and are not tissue specific.

• “Entrez Gene: FDX1 ferredoxin 1”.

Adrenodoxin reductase

Adrenodoxin reductase (Enzyme Nomenclature name: adrenodoxin-NADP+ reductase, EC 1.18.1.6), was first isolated from bovine adrenal cortex where it functions as the first enzyme in the mitochondrial P450 systems that catalyze essential steps in steroid hormone biosynthesis.

• Omura T, Sanders E, Estabrook RW, Cooper DY, Rosenthal O (December 1966). “Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase”. Archives of Biochemistry and Biophysics. 117 (3): 660–673. doi:10.1016/0003-9861(66)90108-1.
• Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.

Examination of complete genome sequences revealed that adrenodoxin reductase gene is present in most metazoans and prokaryotes.

• Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.

Nomenclature

The name of the enzyme was coined based on its function to reduce a [2Fe-2S] (2 iron, 2 sulfur) electron-transfer protein that was named adrenodoxin. Later, in some studies, the enzyme was also referred to as a “ferredoxin reductase”, as adrenodoxin is a ferredoxin. In the human gene nomenclature, the standard name is ferredoxin reductase and the symbol is FDXR, with ADXR specified as a synonym.

The assignment of the name “ferredoxin reductase” has been criticized as a misnomer because determination of the structure of adrenodoxin reductase revealed that it is completely different from that of plant ferredoxin reductase and there is no homology between these two enzymes.

• Hanukoglu I (1996). “Electron transfer proteins of cytochrome P450 systems”. Physiological Functions of Cytochrome P450 in Relation to Structure and Regulation (PDF). Adv. Mol. Cell Biol. Advances in Molecular and Cell Biology. Vol. 14. pp. 29–55. doi:10.1016/S1569-2558(08)60339-2. ISBN 9780762301133.
• Ziegler GA, Vonrhein C, Hanukoglu I, Schulz GE (Jun 1999). “The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis”. Journal of Molecular Biology. 289 (4): 981–90. doi:10.1006/jmbi.1999.2807. PMID 10369776.
• Ziegler GA, Schulz GE (2000). “Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family”. Biochemistry. 39 (36): 10986–95. doi:10.1021/bi000079k. PMID 10998235.

With more proteins with a ferroxodin-reducing activity discovered in both families as well as novel families, this enzyme activity is now seen as an example of convergent evolution.

• Aliverti A, Pandini V, Pennati A, de Rosa M, Zanetti G (June 2008). “Structural and functional diversity of ferredoxin-NADP(+) reductases”. Archives of Biochemistry and Biophysics. 474 (2): 283–91. doi:10.1016/j.abb.2008.02.014. hdl:2434/41439. PMID 18307973.
• Spaans SK, Weusthuis RA, van der Oost J, Kengen SW (2015). “NADPH-generating systems in bacteria and archaea”. Frontiers in Microbiology. 6: 742. doi:10.3389/fmicb.2015.00742. PMC 4518329. PMID 26284036.

Function

Adrenodoxin reductase is a flavoprotein as it carries a FAD type coenzyme. The enzyme functions as the first electron transfer protein of mitochondrial P450 systems such as P450scc.

• Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.

The FAD coenzyme receives two electrons from NADPH and transfers them one at a time to the electron transfer protein adrenodoxin.

• Lambeth JD, Kamin H (Jul 1976). “Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH”. The Journal of Biological Chemistry. 251 (14): 4299–306. doi:10.1016/S0021-9258(17)33296-9. PMID 6475.

Adrenodoxin functions as a mobile shuttle that transfers electrons between ADXR and mitochondrial P450s.

• Hanukoglu I, Jefcoate CR (Apr 1980). “Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin” (PDF). The Journal of Biological Chemistry. 255 (7): 3057–61. doi:10.1016/S0021-9258(19)85851-9. PMID 6766943.

It catalyzes the following reaction:NADPH + 2 oxidized adrenodoxin —→ 2 reduced adrenodoxin + NADP⁺ + H⁺

Gene structure

The cDNA for adrenodoxin reductase was first cloned in 1987.

• 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”. European Journal of Biochemistry. 169 (3): 449–455. doi:10.1111/j.1432-1033.1987.tb13632.x. PMID 3691502.

In both bovine and human genomes there is only a single copy of the gene.

• 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”. European Journal of Biochemistry. 169 (3): 449–455. doi:10.1111/j.1432-1033.1987.tb13632.x. PMID 3691502.
• Solish SB, Picado-Leonard J, Morel Y, Kuhn RW, Mohandas TK, Hanukoglu I, Miller WL (Oct 1988). “Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen—-q25 are expressed in steroidogenic tissues”. Proceedings of the National Academy of Sciences of the United States of America. 85 (19): 7104–7108. Bibcode:1988PNAS…85.7104S. doi:10.1073/pnas.85.19.7104. PMC 282132. PMID 2845396.

Sites of expression

ADXR gene is expressed in all tissues that have mitochondrial P450s. The highest levels of the enzyme are found in the adrenal cortex, granulosa cells of the ovary and leydig cells of the testis that specialize in steroid hormone synthesis.

• Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.
• 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”. European Journal of Biochemistry. 157 (1): 27–31. doi:10.1111/j.1432-1033.1986.tb09633.x. PMID 3011431.

Immmunofluorescent staining shows that enzyme is localized in mitochondria.

• Hanukoglu I, Suh BS, Himmelhoch S, Amsterdam A (October 1990). “Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells”. The Journal of Cell Biology. 111 (4): 1373–81. doi:10.1083/jcb.111.4.1373. PMC 2116250. PMID 2170421.

The enzyme is also expressed in the liver, the kidney and the placenta.

Enzyme structure

Adrenodoxin reductase has two domains that bind NADPH and FAD separately.

• Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.

The FAD and NADP binding sites of the enzyme were predicted by sequence analysis of the enzyme.

• Hanukoglu I, Gutfinger T (Mar 1989). “cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases”. European Journal of Biochemistry. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.

While the FAD-binding site has a consensus sequence (Gly-x-Gly-x-x-Gly) that is similar to other Rossmann folds in FAD and NAD binding sites, the NADPH binding site consensus sequence differs from the FAD-binding site by the substitution of an alanine instead of the last Gly (Gly-x-Gly-x-x-Ala).

• Hanukoglu I, Gutfinger T (Mar 1989). “cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases”. European Journal of Biochemistry. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
• Hanukoglu I (2015). “Proteopedia: Rossmann fold: A beta-alpha-beta fold at dinucleotide binding sites”. Biochem Mol Biol Educ. 43 (3): 206–209. doi:10.1002/bmb.20849. PMID 25704928. S2CID 11857160.
• Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.

The location of these FAD and NADP binding sites were confirmed by the crystal structure of the enzyme.

• Ziegler GA, Schulz GE (2000). “Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family”. Biochemistry. 39 (36): 10986–95. doi:10.1021/bi000079k. PMID 10998235.

References

1. GRCh38: Ensembl release 89: ENSG00000137714 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032051 – Ensembl, May 2017
3. “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
4. “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Mittal S, Zhu YZ, Vickery LE (Sep 1988). “Molecular cloning and sequence analysis of human placental ferredoxin”. Arch Biochem Biophys. 264 (2): 383–91. doi:10.1016/0003-9861(88)90303-7. PMID 2969697.
6. “Entrez Gene: FDX1 ferredoxin 1”.
7. Hanukoglu I, Jefcoate CR (Apr 1980). “Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin” (PDF). The Journal of Biological Chemistry. 255 (7): 3057–61. doi:10.1016/S0021-9258(19)85851-9. PMID 6766943.
8. Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.
9. GRCh38: Ensembl release 89: ENSG00000161513 – Ensembl, May 2017
10. GRCm38: Ensembl release 89: ENSMUSG00000018861 – Ensembl, May 2017
11. “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
12. “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
13. Omura T, Sanders E, Estabrook RW, Cooper DY, Rosenthal O (December 1966). “Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase”. Archives of Biochemistry and Biophysics. 117 (3): 660–673. doi:10.1016/0003-9861(66)90108-1.
14. Hanukoglu I (Dec 1992). “Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis”. The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.
15. Hanukoglu I (2017). “Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme”. Journal of Molecular Evolution. 85 (5): 205–218. Bibcode:2017JMolE..85..205H. doi:10.1007/s00239-017-9821-9. PMID 29177972. S2CID 7120148.
16. Hanukoglu I (1996). “Electron transfer proteins of cytochrome P450 systems”. Physiological Functions of Cytochrome P450 in Relation to Structure and Regulation (PDF). Adv. Mol. Cell Biol. Advances in Molecular and Cell Biology. Vol. 14. pp. 29–55. doi:10.1016/S1569-2558(08)60339-2. ISBN 9780762301133.
17. Ziegler GA, Vonrhein C, Hanukoglu I, Schulz GE (Jun 1999). “The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis”. Journal of Molecular Biology. 289 (4): 981–90. doi:10.1006/jmbi.1999.2807. PMID 10369776.
18. Ziegler GA, Schulz GE (2000). “Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family”. Biochemistry. 39 (36): 10986–95. doi:10.1021/bi000079k. PMID 10998235.
19. Aliverti A, Pandini V, Pennati A, de Rosa M, Zanetti G (June 2008). “Structural and functional diversity of ferredoxin-NADP(+) reductases”. Archives of Biochemistry and Biophysics. 474 (2): 283–91. doi:10.1016/j.abb.2008.02.014. hdl:2434/41439. PMID 18307973.
20. Spaans SK, Weusthuis RA, van der Oost J, Kengen SW (2015). “NADPH-generating systems in bacteria and archaea”. Frontiers in Microbiology. 6: 742. doi:10.3389/fmicb.2015.00742. PMC 4518329. PMID 26284036.
21. Lambeth JD, Kamin H (Jul 1976). “Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH”. The Journal of Biological Chemistry. 251 (14): 4299–306. doi:10.1016/S0021-9258(17)33296-9. PMID 6475.
22. Hanukoglu I, Jefcoate CR (Apr 1980). “Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin” (PDF). The Journal of Biological Chemistry. 255 (7): 3057–61. doi:10.1016/S0021-9258(19)85851-9. PMID 6766943.
23. 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”. European Journal of Biochemistry. 169 (3): 449–455. doi:10.1111/j.1432-1033.1987.tb13632.x. PMID 3691502.
24. Solish SB, Picado-Leonard J, Morel Y, Kuhn RW, Mohandas TK, Hanukoglu I, Miller WL (Oct 1988). “Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen—-q25 are expressed in steroidogenic tissues”. Proceedings of the National Academy of Sciences of the United States of America. 85 (19): 7104–7108. Bibcode:1988PNAS…85.7104S. doi:10.1073/pnas.85.19.7104. PMC 282132. PMID 2845396.
25. 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”. European Journal of Biochemistry. 157 (1): 27–31. doi:10.1111/j.1432-1033.1986.tb09633.x. PMID 3011431.
26. Hanukoglu I, Suh BS, Himmelhoch S, Amsterdam A (October 1990). “Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells”. The Journal of Cell Biology. 111 (4): 1373–81. doi:10.1083/jcb.111.4.1373. PMC 2116250. PMID 2170421.
27. Hanukoglu I, Gutfinger T (Mar 1989). “cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases”. European Journal of Biochemistry. 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
28. Hanukoglu I (2015). “Proteopedia: Rossmann fold: A beta-alpha-beta fold at dinucleotide binding sites”. Biochem Mol Biol Educ. 43 (3): 206–209. doi:10.1002/bmb.20849. PMID 25704928. S2CID 11857160.

Further reading

Adrendoxin

• Grinberg AV, Hannemann F, Schiffler B, et al. (2000). “Adrenodoxin: structure, stability, and electron transfer properties”. Proteins. 40 (4): 590–612. doi:10.1002/1097-0134(20000901)40:4<590::AID-PROT50>3.0.CO;2-P. PMID 10899784. S2CID 113757.
• Wada A, Waterman MR (1992). “Identification by site-directed mutagenesis of two lysine residues in cholesterol side chain cleavage cytochrome P450 that are essential for adrenodoxin binding”. J. Biol. Chem. 267 (32): 22877–82. doi:10.1016/S0021-9258(18)50028-4. PMID 1429635.
• 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.
• Skjeldal L, Markley JL, Coghlan VM, Vickery LE (1991). “1H NMR spectra of vertebrate [2Fe-2S] ferredoxins. Hyperfine resonances suggest different electron delocalization patterns from plant ferredoxins”. Biochemistry. 30 (37): 9078–83. doi:10.1021/bi00101a024. PMID 1909889.
• 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. doi:10.1016/S0021-9258(18)55106-1. PMID 1917982.
• Chang CY, Wu DA, Mohandas TK, Chung BC (1990). “Structure, sequence, chromosomal location, and evolution of the human ferredoxin gene family”. DNA Cell Biol. 9 (3): 205–12. doi:10.1089/dna.1990.9.205. PMID 2340092.
• Chang CY, Wu DA, Lai CC, et al. (1989). “Cloning and structure of the human adrenodoxin gene”. DNA. 7 (9): 609–15. doi:10.1089/dna.1988.7.609. PMID 3229285.
• Voutilainen R, Picado-Leonard J, DiBlasio AM, Miller WL (1988). “Hormonal and developmental regulation of adrenodoxin messenger ribonucleic acid in steroidogenic tissues”. J. Clin. Endocrinol. Metab. 66 (2): 383–8. doi:10.1210/jcem-66-2-383. PMID 3339111.
• Picado-Leonard J, Voutilainen R, Kao LC, et al. (1988). “Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells”. J. Biol. Chem. 263 (7): 3240–4. doi:10.1016/S0021-9258(18)69061-1. PMID 3343244.
• Martsev SP, Chashchin VL, Akhrem AA [in Belarusian] (1985). “[Reconstruction and study of a multi-enzyme system by 11 beta-hydroxylase steroids]”. Biokhimiia. 50 (2): 243–57. PMID 3872685.
• Geren LM, Millett F (1981). “Fluorescence energy transfer studies of the interaction between adrenodoxin and cytochrome c”. J. Biol. Chem. 256 (20): 10485–9. doi:10.1016/S0021-9258(19)68647-3. PMID 6270113.
• Pikuleva IA, Cao C, Waterman MR (1999). “An additional electrostatic interaction between adrenodoxin and P450c27 (CYP27A1) results in tighter binding than between adrenodoxin and p450scc (CYP11A1)”. J. Biol. Chem. 274 (4): 2045–52. doi:10.1074/jbc.274.4.2045. PMID 9890963.
• Kostic M, Pochapsky SS, Obenauer J, et al. (2002). “Comparison of functional domains in vertebrate-type ferredoxins”. Biochemistry. 41 (19): 5978–89. doi:10.1021/bi0200256. PMID 11993992.
• 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. Bibcode:2002PNAS…9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Johnson D, Norman S, Tuckey RC, Martin LL (2004). “Electrochemical behaviour of human adrenodoxin on a pyrolytic graphite electrode”. Bioelectrochemistry. 59 (1–2): 41–7. doi:10.1016/s1567-5394(02)00188-3. PMID 12699818.
• 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.
• 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.
• Derouet-Hümbert E, Roemer K, Bureik M (2005). “Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria”. Biol. Chem. 386 (5): 453–61. doi:10.1515/BC.2005.054. PMID 15927889. S2CID 37533711.

Adrenodoxin reductase

• Sparkes RS, Klisak I, Miller WL (Jun 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 and Cell Biology. 10 (5): 359–65. doi:10.1089/dna.1991.10.359. PMID 1863359.
• Coghlan VM, Vickery LE (Oct 1991). “Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc”. The Journal of Biological Chemistry. 266 (28): 18606–12. doi:10.1016/S0021-9258(18)55106-1. PMID 1917982.
• Lin D, Shi YF, Miller WL (Nov 1990). “Cloning and sequence of the human adrenodoxin reductase gene”. Proceedings of the National Academy of Sciences of the United States of America. 87 (21): 8516–20. Bibcode:1990PNAS…87.8516L. doi:10.1073/pnas.87.21.8516. PMC 54987. PMID 2236061.
• Usanov SA, Chernogolov AA, Honkakoski P, Lang M, Passanen M, Raunio H, Pelkonen O (May 1990). “[Cholesterol-hydroxylating cytochrome P-450 from bovine adrenal cortex mitochondria and human placenta: immunochemical properties and structural characteristics]”. Biokhimiya. 55 (5): 865–77. PMID 2393675.
• Sasano H, Sasano N, Okamoto M, Nonaka Y (May 1989). “Immunohistochemical demonstration of adrenodoxin reductase in bovine and human adrenals”. Pathology, Research and Practice. 184 (5): 473–9. doi:10.1016/s0344-0338(89)80137-2. PMID 2748461.
• Usanov SA, Honkakoski P, Lang MA, Pasanen M, Pelkonen O, Raunio H (Oct 1989). “Comparison of the immunochemical properties of human placental and bovine adrenal cholesterol side-chain cleavage enzyme complex”. Biochimica et Biophysica Acta (BBA) – Protein Structure and Molecular Enzymology. 998 (2): 189–95. doi:10.1016/0167-4838(89)90272-0. PMID 2790061.
• Maruyama K, Sugano S (Jan 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.
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External links

• Human FDX1 genome location and FDX1 gene details page in the UCSC Genome Browser.

• Human FDXR genome location and FDXR gene details page in the UCSC Genome Browser.

Categories: 

• Genes on human chromosome 11
• Human chromosome 11 gene stubs