Electron transport chain

A continuous supply of energy in the form of ATP is essential to the maintenance of life. In most eukaryotes, it is achieved by oxygen-dependent energy production and mitochondrial electron transport chain plays central role in ATP production. In higher eukaryotes, electron transport chain comprises four integral membrane protein complexes namely, NADH:ubiquinone oxidoreductase (complex I), succinate:ubiquinone oxidoreductase (complex II), ubiquinol:cytochrome c oxidoreductase/ cytochrome bc1 complex (complex III) and cytochrome oxidase (complex IV).  The electrons are transferred from NADH and succinate to oxygen through these series of enzymatic complexes of the inner mitochondrial membrane and oxygen is reduced to water. This releases energy and generates a proton gradient across mitochondrial membrane by pumping protons into intermembrane space. The energy of oxidation of hydrogen is used to phosphorylate ADP into ATP. This ATP generation is catalysed by ATP synthase complex (complex V).


The conventional NADH:ubiquinone oxidoreductase multiprotein complex is absent in apicomplexan genomes. However, an alternative single gene NAD(P)H dehydrogenase enzyme homologous to the peripheral membrane NADH dehydrogenase in yeast, plants and fungi was identified in Plasmodium falciparum genome. This enzyme is rotenone insensitive [1, 2, 3, 4]. The orthologs of this enzyme are present in the Piroplasma species such as Theileria parva, Theileria annulata and Babesia bovis. The analysis of Piroplasma genomes shows the presence of only two sub units of succinate dehydrogenase (flavoprotein subunit and iron-sulphur protein subunits). The orthologs of the membrane anchor subunits have not been identified in these genomes. It was also the case with P. falciparum and Toxoplasma gondii genomes. Purification and molecular characterisation of the succinate dehydrogenase in P. falciparum has identified the above mentioned two subunits (flavoprotein subunit and iron-sulphur protein subunits)  and demonstrated significant activity. It is also suggested that this enzyme may be a peripheral complex [4, 5, 6].


The complex III of P. falciparum and T. gondii are similar to mammalian enzymes. The mammalian complex III inhibitors such as myxothiazol and antimycin A can inhibit Plasmodium complex III activity [4]. The differences in the ubiquinol binding regions of Plasmodium cytochrome b to mammalian protein has enabled the use of atovaquone as anti-malarial. Its action in complex III was confirmed by the study showing the resistance to atovoquone in malarial parasites with mutations in ubiquinol binding domains of cytochrome b [7]. The use of related drugs to treat East Coast Fever, an infection of T. parva [8] may suggest the conservation of ubiquinol binding domain of cytochrome b across Apicomplexa including these Piroplasma species. The genes for the two subunits of Cox2, the accessory protein Cox4 and the assembly proteins Cox10, Cox11, Cox12, Cox15, Cox17 and Cox19 are present in the nuclear genomes of these Piroplasma species. The Cox1 and Cox3 are present in the mitochondrial genomes of these species.


The Theileria and Babesia genomes possess the genes for all the F1 subunits and the Fo-c subunit (proteolipid subunit) of ATP synthase complex. The genes for Fo-a and Fo-b are not identified in these species as is the case with P. falciparum and T. gondii. It has been demonstrated in intra-erythrocytic stages of P. falciparum that electron transport chain does not play a role in ATP synthesis and it is only important for regeneration of ubiquinone as an electron acceptor for dihydroorotate dehydrogenase. It has also been proposed that the hydrolysis of ATP by matrix localised ATP synthase and transport of ADP for ATP will generate net negative charge and establishes membrane potential [9]. The presence of pyrimidine biosynthesis in Piroplasma suggests the role of this pathway in regeneration of ubiquinone. The role of this pathway in energy generation is yet to be confirmed in these species.


Enzyme EC Number Gene id Mitochondrial Complex
Glycerol-3-phosphate dehydrogenase BBOV_IV004480  
Glycerol-3-phosphate dehydrogenase BBOV_III000930  
Malate:quinone oxidoreductase BBOV_III000580  
Ubiquinol cytochrome c oxidoreductase bc1 complex hinge protein BBOV_II002140 Cytochrome bc1 complex (Complex III)
Ubiquinol cytochrome c oxidoreductase bc1 complex Fe-S subunit BBOV_III009930 Cytochrome bc1 complex (Complex III)
Ubiquinol cytochrome c oxidoreductase bc1 complex 14kDa subunit BBOV_IV009120 Cytochrome bc1 complex (Complex III)
Flavoprotein subunit of succinate dehydrogenase BBOV_IV007210 Succinate dehydrogenase (ubiquinone) complex (Complex II)
Dihydroorotate dehydrogenase BBOV_II007190  
Iron-sulfur centres of succinate dehydrogenase BBOV_IV005280 Succinate dehydrogenase (ubiquinone) complex (Complex II)
NAD(P)H dehydrogenase BBOV_I004980  
Cox12 BBOV_I001580 Cytochrome c oxidase (Complex IV)
Cox10 BBOV_II003260 Cytochrome c oxidase (Complex IV)
Cox17 BBOV_III000120 Cytochrome c oxidase (Complex IV)
Cox15 BBOV_III002290 Cytochrome c oxidase (Complex IV)
Cox4 BBOV_III010970 Cytochrome c oxidase (Complex IV)
Cox2 BBOV_IV000710 Cytochrome c oxidase (Complex IV)
Cox11 BBOV_IV000820 Cytochrome c oxidase (Complex IV)
Cox19 BBOV_IV008710 Cytochrome c oxidase (Complex IV)
Cox19 BBOV_IV008720 Cytochrome c oxidase (Complex IV)
Cox2 BBOV_IV010440 Cytochrome c oxidase (Complex IV)
Cox1 BBOV_VI000010 (Mitochondrial genome) Cytochrome c oxidase (Complex IV)
Cox3 BBOV_VI000020 (Mitochondrial genome) Cytochrome c oxidase (Complex IV)
ATP synthase alpha chain BBOV_III002130 ATP synthase (Complex V)
ATP synthase delta subunit BBOV_III004400 ATP synthase (Complex V)
ATP synthase lipid-binding protein (Fo-c subunit) BBOV_III004620 ATP synthase (Complex V)
ATP synthase gamma chain BBOV_IV005350 ATP synthase (Complex V)
ATP synthase beta chain BBOV_IV005830 ATP synthase (Complex V)
ATP synthase epsilon chain BBOV_IV007710 ATP synthase (Complex V)
ATP synthase subunit O BBOV_IV008470 ATP synthase (Complex V)
ATP synthase Fo-a subunit Missing in annotation ATP synthase (Complex V)
ATP synthase Fo-b subunit Missing in annotation ATP synthase (Complex V)
Cytochrome c1 none BBOV_II002550 Cytochrome bc1 complex (Complex III)
Cytochrome c none BBOV_III005520  
Cytochrome c none BBOV_III008130  
Cytochrome b none BBOV_VI000060 (Mitochondrial genome) Cytochrome bc1 complex (Complex III)


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Sources and fates of metabolites


Substrate Source pathways Product Fate pathways
Malate Tricarboxylic acid (TCA) cycle Oxaloacetate Tricarboxylic acid (TCA) cycle
L-dihydroorotate Pyrimidine metabolism Orotate Pyrimidine metabolism
Succinate Tricarboxylic acid (TCA) cycle Fumarate Tricarboxylic acid (TCA) cycle