Electron transport chain (Incomplete pathway)

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 the genomes of Plasmodium falciparum and Toxoplasma gondii and Cryptosporidium species. 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 P. falciparum genome. These alternative NADH dehydrogenases of mitochondrial membrane are insensitive to rotenone, an inhibitor of complex I [1]. The presence of oxidation of exogenous NADH and its insensitivity to rotenone has been experimentally shown in P. falciparum and Plasmodium yoelii yoelii. This confirms the presence of alternative NADH dehydrogenase in these species [2, 3, 4]. The analysis of Cryptosporidium genomes has showed that they also possess NAD(P)H dehydrogenase which are orthologous to the Plasmodium alternative NAD(P)H dehydrogenase.

 

The analysis of the genomes of Cryptosporidium parvum and Cryptosporidium hominis showed the absence of succinate dehydrogenase complex II as opposed to Cryptosporidium muris where this complex is present. The complex III and complex IV are absent in the genomes of all three Cryptosporidium species. The absence of any beneficial effect with atovaquone treatment for mice infected with C. parvum suggested the absence of classical electron transport chain [5]. However, another study showed that inhibition of intracellular growth was observed with 20 out of 30 naphthoquinones tested [6]. These Cryptosporidium species possess a single gene alternative ubiquinol oxidase (AOX). The cloning and expression of C. parvum AOX gene and the inhibition of growth with inhibitors SHAM and 8-hydroxyquinoline has confirmed the presence of alternative oxidase function in Cryptosporidium species [7]. The ATP synthase complex is absent in C. parvum and C. hominis except two subunits (F1-alpha and beta subunits. The genes for these subunits are shorter than those of C. muris and are non-functional. The absence of TCA cycle and complete electron transport chain shows that these species are completely dependent on glycolysis for energy generation.

 

Enzyme EC Number Gene id
Glycerol-3-phosphate dehydrogenase 1.1.1.8 Chro.20028
Alternative oxidase (ubiquinol oxidase) 1.10.3.11 Chro.30354
Malalte:quinone oxidoreductase 1.1.5.4 Chro.80050
NAD(P)H dehydrogenase 1.6.5.3 Chro.70218
ATP synthase beta chain 3.6.3.14 Chro.20148 (non functional)
ATP synthase alpha chain 3.6.3.14 Chro.60082 (non functional)