Eukaryotes cytochrome biosynthesis

In order to identify a eukaryotic iron transporter, we chose to work with the yeast Saccharomyces cerevisiae because of its tractable genetic system and the simplicity and redundancy of its iron transporters. S. cerevisiae employs two main methods to obtain iron from the environment. One, they possess a siderophore-dependent iron transport system [10]. While S. cerevisiae is able to use siderophores secreted by other microorganisms, it does not make or secrete siderophores [11]. Two, in laboratory conditions S. cerevisiae must rely on elemental iron transport which depends on cell surface ferrireductases to convert extracellular ferric chelates to ferrous iron [12]. Two yeast ferrireductase genes FREl and FRE2 are transcriptionally induced by iron need and have been shown to play a role in iron transport [13, 14]. The ferrireductases possess multiple transmembrane domains and potential FAD and NADPH binding domains. These ferrireductases use intracellular NADPH as an electron donor for the conversion of ferric iron to ferrous (Figure 4-1) [15]. The ferrireductases also require heme biosynthesis for function and bind two heme molecules in a maimer similar to the B-type cytochromes [16],... 

Heme A is an obligatory cofactor in all eukaryotic and most bacterial cytochrome c oxidase enzymes (CcO). Because of its importance to CcO and aerobic metabolism, considerable effort has recently been invested in understanding the mechanism and regulation of heme A biosynthesis. The activity of heme A synthase is strictly dependent on O2, and yet there is no incorporation of O2 into the products. Heme A synthase is now known to utilize a unique electron-transfer mechanism when oxidizing heme O to heme A. Interestingly, the heme A biosynthetic pathway is regulated at least partly via a heme-dependent process in which heme A synthase is positively regulated by intracellular heme levels via Hapl. 

Coenzymes such as NAD, NADP and coenzyme A are concentrated in the aqueous phase of the matrix. The matrix also contains the protein synthesizing system of the M. Vertebrate M. contain Ribosomes (see) of size 50-55S, whereas the M. of other eukaryotic organisms contain 70S ribosomes. The DNA of M. is circular, histone-free, and attains a length (in mammals) of 5 pm. It contains cistrons for ribosomal RNA and tRNA, and the genes for ATPases, for 2 of the 3 subunits of cytochrome 6, and for 4 of the 7 subunits of cytochrome oxidase. The biosynthesis of all the other mitochondrial constituents appears to be under the genetic control of the cell nucleus. The genetic code and tRNA complement of M. are different from those of the cytoplasm (see Genetic code). 

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