Adrenal ferredoxin explained

Adrenal ferredoxin (also adrenodoxin (ADX), adrenodoxin, mitochondrial, hepatoredoxin, ferredoxin-1 (FDX1)) is a protein that in humans is encoded by the FDX1 gene.^{[1] [2]} 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.^[3] The first enzyme in this system is adrenodoxin reductase that carries an FAD. FAD can be reduced by two electrons donated from coenzyme NADPH.^[4] These two electrons are transferred one a time to adrenodoxin. Adrenodoxin in return reduces mitochondrial cytochrome P450. 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.

Further reading

• Grinberg AV, Hannemann F, Schiffler B . Adrenodoxin: structure, stability, and electron transfer properties . Proteins . 40 . 4 . 590–612 . 2000 . 10899784 . 10.1002/1097-0134(20000901)40:4<590::AID-PROT50>3.0.CO;2-P . 113757 . etal.
• Wada A, Waterman MR . 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 . 1992 . 10.1016/S0021-9258(18)50028-4 . 1429635 . free .
• Sparkes RS, Klisak I, Miller WL . 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 . 1991 . 1863359 . 10.1089/dna.1991.10.359 .
• Skjeldal L, Markley JL, Coghlan VM, Vickery LE . 1H NMR spectra of vertebrate [2Fe-2S] ferredoxins. Hyperfine resonances suggest different electron delocalization patterns from plant ferredoxins . Biochemistry . 30 . 37 . 9078–83 . 1991 . 1909889 . 10.1021/bi00101a024 .
• Coghlan VM, Vickery LE . Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc . J. Biol. Chem. . 266 . 28 . 18606–12 . 1991 . 10.1016/S0021-9258(18)55106-1 . 1917982 . free .
• Chang CY, Wu DA, Mohandas TK, Chung BC . Structure, sequence, chromosomal location, and evolution of the human ferredoxin gene family . DNA Cell Biol. . 9 . 3 . 205–12 . 1990 . 2340092 . 10.1089/dna.1990.9.205 .
• Chang CY, Wu DA, Lai CC . Cloning and structure of the human adrenodoxin gene . DNA . 7 . 9 . 609–15 . 1989 . 3229285 . 10.1089/dna.1988.7.609 . etal.
• Voutilainen R, Picado-Leonard J, DiBlasio AM, Miller WL . Hormonal and developmental regulation of adrenodoxin messenger ribonucleic acid in steroidogenic tissues . J. Clin. Endocrinol. Metab. . 66 . 2 . 383–8 . 1988 . 3339111 . 10.1210/jcem-66-2-383 .
• Picado-Leonard J, Voutilainen R, Kao LC . Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells . J. Biol. Chem. . 263 . 7 . 3240–4 . 1988 . 10.1016/S0021-9258(18)69061-1 . 3343244 . etal. free .
• Martsev SP, Chashchin VL, Akhrem AA .

  be:Афанасій Андрэевіч Ахрэм

  . [Reconstruction and study of a multi-enzyme system by 11 beta-hydroxylase steroids] . Biokhimiia . 50 . 2 . 243–57 . 1985 . 3872685 .
• Geren LM, Millett F . Fluorescence energy transfer studies of the interaction between adrenodoxin and cytochrome c . J. Biol. Chem. . 256 . 20 . 10485–9 . 1981 . 10.1016/S0021-9258(19)68647-3 . 6270113 . free .
• Pikuleva IA, Cao C, Waterman MR . 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 . 1999 . 9890963 . 10.1074/jbc.274.4.2045 . free.
• Kostic M, Pochapsky SS, Obenauer J . Comparison of functional domains in vertebrate-type ferredoxins . Biochemistry . 41 . 19 . 5978–89 . 2002 . 11993992 . 10.1021/bi0200256 . etal.
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Johnson D, Norman S, Tuckey RC, Martin LL . Electrochemical behaviour of human adrenodoxin on a pyrolytic graphite electrode . Bioelectrochemistry. 59 . 1–2 . 41–7 . 2004 . 12699818 . 10.1016/s1567-5394(02)00188-3.
• Araya Z, Hosseinpour F, Bodin K, Wikvall K . 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 . 2003 . 12782149 . 10.1016/S1388-1981(03)00062-3.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Derouet-Hümbert E, Roemer K, Bureik M . Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria . Biol. Chem. . 386 . 5 . 453–61 . 2005 . 15927889 . 10.1515/BC.2005.054 . 37533711 .

Notes and References

1. Mittal S, Zhu YZ, Vickery LE . Molecular cloning and sequence analysis of human placental ferredoxin . Arch Biochem Biophys . 264 . 2 . 383–91 . Sep 1988 . 2969697 . 10.1016/0003-9861(88)90303-7 .
2. Web site: Entrez Gene: FDX1 ferredoxin 1.
3. Hanukoglu I, Jefcoate CR . Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin . The Journal of Biological Chemistry . 255 . 7 . 3057–61 . Apr 1980 . 10.1016/S0021-9258(19)85851-9 . 6766943 . free .
4. Hanukoglu I . Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme . Journal of Molecular Evolution . 85 . 5 . 205–218 . 2017 . 29177972 . 10.1007/s00239-017-9821-9 . 2017JMolE..85..205H . 7120148 .