Lipoic acid incorporation
Lipoic acid is an essential cofactor of dehydrogenase enzymes, mainly the E2 subunit of pyruvate dehydrogenase, branched-chain keto-acid dehydrogenase and 2-oxoglutarate dehydrogenase complexes. Lipoic acid is an organic sulphur compound derived from the 8-carbon fatty acid, octanoic acid. In most eukaryotes, lipoic acid is synthesised in mitochondrion and it is consistent with the localisation of above mentioned three complexes in mitochondria. In apicomplexan parasites, pyruvate dehydrogenase complex is localised in the plastid organelle, apicoplast. The apicoplast is lost in Cryptosporidium species and all the pathways associated with apicoplast in other Apicomplexa including the pyruvate dehydrogenase complex is absent. The only mitochondrial dehydrogenase complex present in C. muris is 2-oxoglutarate dehydrogenase of TCA cycle. The work by Crawford et al in Toxoplasma gondii demonstrated that apicoplast synthesises lipoic acid de novo, whereas mitochondria salvages it from host . The identification of lipoic acid salvage enzyme in Cryptosporidium muris genome suggests that the salvage pathway is also present in C. muris. This enzyme is absent in Cryptosporidium parvum and Cryptosporidium hominis and this is consistent with the absence of TCA cycle in these organisms.
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