Editing Ferredoxin (section)

== Bioenergetics of ferredoxins ==
Ferredoxins typically carry out a single electron transfer.

: {{chem|Fd|ox|''0''}} + {{e-}} <chem><=></chem> {{chem|Fd|red|-}}

However a few bacterial ferredoxins (of the 2[4Fe4S] type) have two iron sulfur clusters and can carry out two electron transfer reactions. Depending on the sequence of the protein, the two transfers can have nearly identical reduction potentials or they may be significantly different.<ref name="MaioccoArcinas2019">{{cite journal | vauthors = Maiocco SJ, Arcinas AJ, Booker SJ, Elliott SJ | title = Parsing redox potentials of five ferredoxins found within Thermotoga maritima | journal = Protein Science | volume = 28 | issue = 1 | pages = 257–266 | date = January 2019 | pmid = 30418685 | doi = 10.1002/pro.3547 | pmc = 6295886 | doi-access = free }}</ref><ref name="Gao-SheridanPershad1998">{{cite journal | vauthors = Gao-Sheridan HS, Pershad HR, Armstrong FA, Burgess BK | title = Discovery of a novel ferredoxin from Azotobacter vinelandii containing two [4Fe-4S] clusters with widely differing and very negative reduction potentials | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5514–9 | date = March 1998 | pmid = 9488675 | doi = 10.1074/jbc.273.10.5514 | doi-access = free }}</ref>

: {{chem|Fd|ox|''0''}} + {{e-}} <chem><=></chem> {{chem|Fd|red|-}}

: {{chem|Fd|red|-}} + {{e-}} <chem><=></chem> {{chem|Fd|red|2-}}

Ferredoxins are one of the most reducing biological electron carriers. They typically have a [[reduction potential|mid point potential]] of -420 mV.<ref name=Buckel2018>{{cite journal | vauthors = Buckel W, Thauer RK | title = Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic Respiration With Protons (Ech) or NAD<sup>+</sup> (Rnf) as Electron Acceptors: A Historical Review | journal = Frontiers in Microbiology | volume = 9 | pages = 401 | year = 2018 | pmid = 29593673 | pmc = 5861303 | doi = 10.3389/fmicb.2018.00401 | doi-access = free }}</ref> The reduction potential of a substance in the cell will differ from its midpoint potential depending on the concentrations of its reduced and oxidized forms. For a one electron reaction, the potential changes by [[Nernst equation|around 60 mV]] for each power of ten change in the ratio of the concentration. For example, if the ferredoxin pool is around 95% reduced, the reduction potential will be around -500 mV.<ref name=Huwiler2019>{{cite journal | vauthors = Huwiler SG, Löffler C, Anselmann SE, Stärk HJ, von Bergen M, Flechsler J, Rachel R, Boll M | title = One-megadalton metalloenzyme complex in ''Geobacter metallireducens'' involved in benzene ring reduction beyond the biological redox window | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 6 | pages = 2259–2264 | date = February 2019 | pmid = 30674680 | pmc = 6369795 | doi = 10.1073/pnas.1819636116 | bibcode = 2019PNAS..116.2259H | doi-access = free }}</ref> In comparison, [[Table of standard reduction potentials for half-reactions important in biochemistry|other biological reactions]] mostly have less reducing potentials: for example the primary biosynthetic reductant of the cell, [[NADPH]] has a cellular redox potential of -370 mV ({{chem|E|0}} = -320 mV).

Depending on the sequence of the supporting protein ferredoxins have  reduction potential from around -500 mV<ref name=Buckel2018/><ref name=Li2016>{{cite journal | doi = 10.1016/j.electacta.2016.02.119 | title = The Catalytic Bias of 2-Oxoacid:ferredoxin Oxidoreductase in CO2: Evolution and reduction through a ferredoxin-mediated electrocatalytic assay | year = 2016 | vauthors = Li B, Elliott SJ | journal = Electrochimica Acta | volume = 199 | pages = 349–356 | doi-access =free  }}</ref> to -340 mV.<ref name=Thamer2003>{{cite journal | vauthors = Thamer W, Cirpus I, Hans M, Pierik AJ, Selmer T, Bill E, Linder D, Buckel W | title = A two [4Fe-4S]-cluster-containing ferredoxin as an alternative electron donor for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans | journal = Archives of Microbiology | volume = 179 | issue = 3 | pages = 197–204 | date = March 2003 | pmid = 12610725 | doi = 10.1007/s00203-003-0517-8 | bibcode = 2003ArMic.179..197T | s2cid = 23621034 }}</ref> A single cell can have multiple types of ferredoxins where each type is tuned to optimally carry out different reactions.<ref name=Hanke2004/>

=== Reduction of ferredoxin ===
The highly reducing ferredoxins are reduced either by using another strong reducing agent, or by using some source of energy to "boost" electrons from less reducing sources to the ferredoxin.<ref name="BoydAmenabar2020">{{cite journal | vauthors = Boyd ES, Amenabar MJ, Poudel S, Templeton AS | title = Bioenergetic constraints on the origin of autotrophic metabolism | journal = Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences | volume = 378 | issue = 2165 | pages = 20190151 | date = February 2020 | pmid = 31902344 | doi = 10.1098/rsta.2019.0151 | pmc = 7015307 | bibcode = 2020RSPTA.37890151B | doi-access = free }}</ref>

==== Direct reduction ====
Reactions that reduce Fd include the oxidation of aldehydes to acids like the [[Glyceraldehyde-3-phosphate dehydrogenase (ferredoxin)|glyceraldehyde to glycerate]] reaction (-580 mV), the [[carbon monoxide dehydrogenase]] reaction (-520 mV), and the 2-oxoacid:Fd Oxidoreductase reactions (-500 mV)<ref name=Gibson2016>{{cite journal | vauthors = Gibson MI, Chen PY, Drennan CL | title = A structural phylogeny for understanding 2-oxoacid oxidoreductase function | journal = Current Opinion in Structural Biology | volume = 41 | pages = 54–61 | date = December 2016 | pmid = 27315560 | pmc = 5381805 | doi = 10.1016/j.sbi.2016.05.011 }}</ref><ref name=Li2016/> like the reaction carried out by [[pyruvate synthase]].<ref name=Huwiler2019/>

==== Membrane potential coupled reduction ====
Ferredoxin can also be reduced by using NADH (-320 mV) or {{chem|H|2}} (-414 mV), but these processes are coupled to the consumption of the [[membrane potential]] to power the "boosting" of electrons to the higher energy state.<ref name=Buckel2018/> The [[Rnf complex]] is a widespread membrane protein in [[bacteria]] that [[Reversible reaction|reversibly]] [[Electron transfer|transfers electrons]] between NADH and ferredoxin while pumping {{chem|Na|+}} or {{chem|H|+}} ions across the [[cell membrane]]. The [[chemiosmotic potential]] of the membrane is consumed to power the unfavorable reduction of {{chem|Fd|ox}} by NADH. This reaction is an essential source of {{chem|Fd|-|red}} in many [[autotroph]]ic organisms. If the [[Cell (biology)|cell]] is growing on [[Substrate (biology)|substrates]] that provide excess {{chem|Fd|-|red}}, the Rnf complex can transfer these electrons to {{chem|NAD|+}} and store the resultant energy in the membrane potential.<ref name="WestphalWiechmann2018">{{cite journal | vauthors = Westphal L, Wiechmann A, Baker J, Minton NP, Müller V | title = The Rnf Complex is an Energy-Coupled Transhydrogenase Essential to Reversibly Link Cellular NADH and Ferredoxin Pools in the Acetogen Acetobacterium woodii | journal = Journal of Bacteriology | volume = 200 | issue = 21 | date = November 2018 | pmid = 30126940 | doi = 10.1128/JB.00357-18 | pmc = 6182241 | doi-access = free }}</ref> The energy converting [[hydrogenase]]s (Ech) are a family of [[enzyme]]s that reversibly couple the transfer of electrons between {{chem|Fd}} and {{chem|H|2}} while pumping {{chem|H|+}} ions across the membrane to balance the energy difference.<ref name="SchoelmerichMüller2019">{{cite journal | vauthors = Schoelmerich MC, Müller V | title = Energy-converting hydrogenases: the link between H<sub>2</sub> metabolism and energy conservation | journal = Cellular and Molecular Life Sciences | volume = 77 | issue = 8 | pages = 1461–1481 | date = April 2020 | pmid = 31630229 | doi = 10.1007/s00018-019-03329-5 | s2cid = 204786346 | pmc = 11636919 }}</ref>

: {{chem|Fd|ox|''0''}} + {{chem|NADH}} + {{chem|Na|outside|+}} <chem><=></chem> {{chem|Fd|red|2-}} + {{chem| NAD|+}} + {{chem|Na|inside|+}}

: {{chem|Fd|ox|''0''}} + {{chem|H|2}} + {{chem|H|outside|+}} <chem><=></chem> {{chem|Fd|red|2-}} + {{chem| H|+}} + {{chem|H|inside|+}}

==== Electron bifurcation ====
The unfavourable reduction of Fd from a less reducing [[electron donor]] can be coupled simultaneously with the favourable reduction of an [[oxidizing agent]] through an [[electron bifurcation]] reaction.<ref name=Buckel2018/> An example of the electron bifurcation reaction is the generation of {{chem|Fd|red|-}} for [[nitrogen fixation]] in certain [[Aerobic organism|aerobic]] [[diazotroph]]s. Typically, in [[oxidative phosphorylation]] the transfer of electrons from [[NADH]] to [[ubiquinone]] (Q) is coupled to charging the proton motive force. In ''[[Azotobacter]]'' the energy released by transferring one electron from NADH to Q is used to simultaneously boost the transfer of one electron from NADH to Fd.<ref name=Ledbetter2017>{{cite journal | vauthors = Ledbetter RN, Garcia Costas AM, Lubner CE, Mulder DW, Tokmina-Lukaszewska M, Artz JH, Patterson A, Magnuson TS, Jay ZJ, Duan HD, Miller J, Plunkett MH, Hoben JP, Barney BM, Carlson RP, Miller AF, Bothner B, King PW, Peters JW, Seefeldt LC | title = The Electron Bifurcating FixABCX Protein Complex from Azotobacter vinelandii: Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis | journal = Biochemistry | volume = 56 | issue = 32 | pages = 4177–4190 | date = August 2017 | pmid = 28704608 | pmc = 7610252 | doi = 10.1021/acs.biochem.7b00389 }}</ref><ref name="PoudelColman2018">{{cite journal | vauthors = Poudel S, Colman DR, Fixen KR, Ledbetter RN, Zheng Y, Pence N, Seefeldt LC, Peters JW, Harwood CS, Boyd ES | title = Electron Transfer to Nitrogenase in Different Genomic and Metabolic Backgrounds | journal = Journal of Bacteriology | volume = 200 | issue = 10 | date = May 2018 | pmid = 29483165 | doi = 10.1128/JB.00757-17 | pmc = 5915786 | doi-access = free }}</ref>

==== Direct reduction of high potential ferredoxins ====
Some ferredoxins have a sufficiently high [[redox potential]] that they can be directly reduced by NADPH. One such ferredoxin is [[Adrenal ferredoxin|adrenoxin]] (-274 mV) which takes part in the [[biosynthesis]] of many [[mammal]]ian [[steroid]]s.<ref name="EwenRingle2012">{{cite journal | vauthors = Ewen KM, Ringle M, Bernhardt R | title = Adrenodoxin--a versatile ferredoxin | journal = IUBMB Life | volume = 64 | issue = 6 | pages = 506–12 | date = June 2012 | pmid = 22556163 | doi = 10.1002/iub.1029 | doi-access = free }}</ref> The ferredoxin Fd3 in the [[root]]s of plants that reduces [[nitrate]] and [[sulfite]] has a midpoint potential of -337 mV and is also reduced by NADPH.<ref name=Hanke2004>{{cite journal | vauthors = Hanke GT, Kimata-Ariga Y, Taniguchi I, Hase T | title = A post genomic characterization of Arabidopsis ferredoxins | journal = Plant Physiology | volume = 134 | issue = 1 | pages = 255–64 | date = January 2004 | pmid = 14684843 | pmc = 316305 | doi = 10.1104/pp.103.032755 }}</ref>