This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: alternative oxidase pathway
|Superclasses:||Generation of Precursor Metabolites and Energy → Electron Transfer|
|Generation of Precursor Metabolites and Energy → Respiration → Aerobic Respiration|
Like fermentation, respiration is a process by which electrons are passed from an electron donor to a terminal electron acceptor. However, in respiration the electrons do not pass directly from the donor to the acceptor. Instead, they pass a number of membrane-bound electron carriers that function as a transport chain, passing the electrons from one to another in steps that follow the electrochemical gradients between the electron donor and the acceptor.
Each oxidized member of the electron transfer chain (which can be a flavoprotein, an electron-transfer-related quinone, a cytochrome, or other type of electron carrier) can be reduced by the reduced form of the preceding member, and the electrons flow through the chain all the way to the terminal acceptor, which could be oxygen in the case of aerobic respiration, or another type of molecule in anaerobic respiration.
Known terminal acceptors include organic compounds (fumarate, dimethyl sulfoxide, or trimethylamine N-oxide), or inorganic compounds (nitrate, nitrite, nitrous oxide, chlorate, perchlorate, oxidized manganese ions, ferric iron, gold, selenate, arsenate, sulfate and elemental sulfur).
During the process of electron transfer, a proton gradient is formed across the membrane due to three potential processes:
1. The use of some of the energy associated with the electron transfer for active pumping of protons out of the cell.
2. Exporting protons out of the cell during electron-to-hydrogen transfers.
3. Scalar reactions that consume protons inside the cell, or produce them outside the cell, without actually moving a proton from one compartment to another.
Upon passage of protons back into the cytoplasm, they drive multisubunit ATP synthase enzymes that generate ATP.
About This Pathway
The alternative terminal oxidase pathway is found in the mitochondrial respiratory chain of plants (also known as the electron transport chain, or ETC), as well as some fungi and protists [Saisho97, Ito97, Vanlerberghe95, Veiga00, Dinant01], but is absent from animal mitochondria. Unlike the cytochrome respiratory pathway (see aerobic respiration I (cytochrome c)), the alternative pathway is not coupled to synthesis of ATP and is not inhibited by cyanide. It is however inhibited by substituted hydroxamic acids such as salicylhydroxamic acid (SHAM) and n-propyl-gallate.
Alternative oxidase (AOX) activity was first described as oxygen consumption in the presence of cyanide from the study of lily pollen and was later found in high levels in the thermogenic inflorescences of the unusual group of plants belonging to the family Araceae. In this family AOX allows rapid, uncoupled respiration, leading to a characteristic heating of the inflorescence [Meeuse75]. This process, also known as thermogenesis, uses the heat produced during flowering to volatize a compound that attracts pollinating insects. In other, more typical plant species, AOX activity has been proposed to be involved in response to oxidative stress [Moller01]. There, AOX would be used to minimize the formation of reactive oxygen species by preventing the overreduction of the ETC.
The pathway has drawn special interest as a target for anti-parasite therapeutics since it was shown to play a key role in the respiration of the trypanosome, better known as the causative agent of African sleeping sickness [Chaudhuri]. The alternative pathway branches from the cytochrome pathway in the inner mitochondrial membrane at the ubiquinone pool and passes electrons to a single terminal oxidase, the alternative oxidase. This protein reduces molecular oxygen to water in a single four-electron transfer step. The electron transport through the alternative oxidase from ubiquinone to water does not contribute to the transmembrane potential and wastes two of the three coupling sites that are part of the cytochrome pathway. Some energy production is nevertheless achieved through the phosphorylating potential of NADH dehydrogenase (NADH-ubiquinone oxidoreductase) [Vanlerberghe97].
Unification Links: AraCyc:PWY-4302
Berthold02: Berthold DA, Voevodskaya N, Stenmark P, Graslund A, Nordlund P (2002). "EPR studies of the mitochondrial alternative oxidase. Evidence for a diiron carboxylate center." J Biol Chem 277(46);43608-14. PMID: 12215444
Chaudhuri: Chaudhuri M, Ajayi W, Temple S, Hill GC "Identification and partial purification of a stage-specific 33 kDa mitochondrial protein as the alternative oxidase of the Trypanosoma brucei brucei bloodstream trypomastigotes." J Eukaryot Microbiol 42(5);467-72. PMID: 7581322
Dinant01: Dinant M, Baurain D, Coosemans N, Joris B, Matagne RF (2001). "Characterization of two genes encoding the mitochondrial alternative oxidase in Chlamydomonas reinhardtii." Curr Genet 39(2);101-8. PMID: 11405094
Franz07: Franz B, Lichtenberg H, Hormes J, Modrow H, Dahl C, Prange A (2007). "Utilization of solid "elemental" sulfur by the phototrophic purple sulfur bacterium Allochromatium vinosum: a sulfur K-edge X-ray absorption spectroscopy study." Microbiology 153(Pt 4);1268-74. PMID: 17379736
Ito97: Ito Y, Saisho D, Nakazono M, Tsutsumi N, Hirai A (1997). "Transcript levels of tandem-arranged alternative oxidase genes in rice are increased by low temperature." Gene 203(2);121-9. PMID: 9426242
Moller01: Moller I.M. "Plant mitochondria and oxidative stress: Electron Transport, NADPH Turnover, and Metabolism of Reactive Oxygen Species." Annual Review of Plant Physiology and Plant Molecular Biology (2001) 52 : 561-591.
Saisho97: Saisho D, Nambara E, Naito S, Tsutsumi N, Hirai A, Nakazono M (1997). "Characterization of the gene family for alternative oxidase from Arabidopsis thaliana." Plant Mol Biol 35(5);585-96. PMID: 9349280
Vanlerberghe95: Vanlerberghe GC, Day DA, Wiskich JT, Vanlerberghe AE, McIntosh L (1995). "Alternative Oxidase Activity in Tobacco Leaf Mitochondria (Dependence on Tricarboxylic Acid Cycle-Mediated Redox Regulation and Pyruvate Activation)." Plant Physiol 109(2);353-361. PMID: 12228600
Veiga00: Veiga A, Arrabaca JD, Loureiro-Dias MC (2000). "Cyanide-resistant respiration is frequent, but confined to yeasts incapable of aerobic fermentation." FEMS Microbiol Lett 190(1);93-7. PMID: 10981696
Battchikova05: Battchikova N, Zhang P, Rudd S, Ogawa T, Aro EM (2005). "Identification of NdhL and Ssl1690 (NdhO) in NDH-1L and NDH-1M complexes of Synechocystis sp. PCC 6803." J Biol Chem 280(4);2587-95. PMID: 15548534
Braun98: Braun M, Bungert S, Friedrich T (1998). "Characterization of the overproduced NADH dehydrogenase fragment of the NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli." Biochemistry 37(7);1861-7. PMID: 9485311
Calhoun93: Calhoun MW, Gennis RB (1993). "Demonstration of separate genetic loci encoding distinct membrane-bound respiratory NADH dehydrogenases in Escherichia coli." J Bacteriol 1993;175(10);3013-9. PMID: 8387992
Crichton05: Crichton PG, Affourtit C, Albury MS, Carre JE, Moore AL (2005). "Constitutive activity of Sauromatum guttatum alternative oxidase in Schizosaccharomyces pombe implicates residues in addition to conserved cysteines in alpha-keto acid activation." FEBS Lett 579(2);331-6. PMID: 15642340
Euro09a: Euro L, Belevich G, Bloch DA, Verkhovsky MI, Wikstrom M, Verkhovskaya M (2009). "The role of the invariant glutamate 95 in the catalytic site of Complex I from Escherichia coli." Biochim Biophys Acta 1787(1);68-73. PMID: 19061856
Figueroa02: Figueroa P, Leon G, Elorza A, Holuigue L, Araya A, Jordana X (2002). "The four subunits of mitochondrial respiratory complex II are encoded by multiple nuclear genes and targeted to mitochondria in Arabidopsis thaliana." Plant Mol Biol 50(4-5);725-34. PMID: 12374303
Finel94: Finel M, Majander A (1994). "Studies on the proton-translocating NADH:ubiquinone oxidoreductases of mitochondria and Escherichia coli using the inhibitor 1,10-phenanthroline." FEBS Lett 339(1-2);142-6. PMID: 8313963
Hayashi89: Hayashi M, Miyoshi T, Takashina S, Unemoto T (1989). "Purification of NADH-ferricyanide dehydrogenase and NADH-quinone reductase from Escherichia coli membranes and their roles in the respiratory chain." Biochim Biophys Acta 977(1);62-9. PMID: 2679883
Heazlewood03: Heazlewood JL, Howell KA, Millar AH (2003). "Mitochondrial complex I from Arabidopsis and rice: orthologs of mammalian and fungal components coupled with plant-specific subunits." Biochim Biophys Acta 1604(3);159-69. PMID: 12837548
Hellwig00: Hellwig P, Scheide D, Bungert S, Mantele W, Friedrich T (2000). "FT-IR spectroscopic characterization of NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli: oxidation of FeS cluster N2 is coupled with the protonation of an aspartate or glutamate side chain." Biochemistry 39(35);10884-91. PMID: 10978175
Kita78: Kita K, Yamato I, Anraku Y (1978). "Purification and properties of cytochrome b556 in the respiratory chain of aerobically grown Escherichia coli K12." J Biol Chem 253(24);8910-5. PMID: 363711
Kita89: Kita K, Vibat CR, Meinhardt S, Guest JR, Gennis RB (1989). "One-step purification from Escherichia coli of complex II (succinate: ubiquinone oxidoreductase) associated with succinate-reducible cytochrome b556." J Biol Chem 264(5);2672-7. PMID: 2644269
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