Mitochondria cytochrome

The link with the final electron acceptor, O2, is the enzyme cytochrome c oxidase which spans the inner membrane of the mitochondrion. It consists of cytochromes a and a3 along with two, or possibly three, Cu atoms. The details of its action are not fully established but the overall reaction catalysed by the enzyme is ... 

Mitochondrial DNA is inherited maternally. What makes mitochondrial diseases particularly interesting from a genetic point of view is that the mitochondrion has its own DNA (mtDNA) and its own transcription and translation processes. The mtDNA encodes only 13 polypeptides nuclear DNA (nDNA) controls the synthesis of 90-95% of all mitochondrial proteins. All known mito-chondrially encoded polypeptides are located in the inner mitochondrial membrane as subunits of the respiratory chain complexes (Fig. 42-3), including seven subunits of complex I the apoprotein of cytochrome b the three larger subunits of cytochrome c oxidase, also termed complex IV and two subunits of ATPase, also termed complex V. 

As mentioned, although complexes I through V are all integrated into the inner membrane of the mitochondrion, they are not usually in contact with one another, since the electrons are transferred by ubiquinone and cytochrome c. With its long apolar side chain, ubiquinone is freely mobile within the membrane. Cytochrome c is water-soluble and is located on the outside of the inner membrane. 

Oxidizible substrates from glycolysis, fatty acid or protein catabolism enter the mitochondrion in the form of acetyl-CoA, or as other intermediaries of the Krebs cycle, which resides within the mitochondrial matrix. Reducing equivalents in the form of NADH and FADH pass electrons to complex I (NADH-ubiquinone oxidore-ductase) or complex II (succinate dehydrogenase) of the electron transport chain, respectively. Electrons pass from complex I and II to complex III (ubiquinol-cyto-chrome c oxidoreductase) and then to complex IV (cytochrome c oxidase) which accumulates four electrons and then tetravalently reduces O2 to water. Protons are pumped into the inner membrane space at complexes I, II and IV and then diffuse down their concentration gradient through complex V (FoFi-ATPase), where their potential energy is captured in the form of ATP. In this way, ATP formation is coupled to electron transport and the formation of water, a process termed oxidative phosphorylation (OXPHOS). 

In this model, cellular stress mediates the release of cytochrome C from the mitochondrion. The proapoptotic proteins Bax and BH3 proteins support the release of cytochrome C, while the antiapoptotic Bcl2 protein has an inhibitory effect. Cytosolic cytochrome C binds to the cofactor Apaf 1, which then associates via its CARD motif with procaspase 9 to a complex termed apopto-some. In this complex, procaspase 9 is processed to the mature caspase which subsequently activates downstream effector caspases and commits the cell to death. 

Because of the difficulty of isolating the electron transport chain from the rest of the mitochondrion, it is easiest to measure ratios of components (Table 18-3). Cytochromes a, a3, b, cv and c vary from a 1 1 to a 3 1 ratio while flavins, ubiquinone, and nonheme iron occur in relatively larger amounts. The much larger... 

What are the molar concentrations of the electron carriers in mitochondrial membranes In one experiment, cytochrome b was found in rat liver mitochondria to the extent of 0.28 pmol/g of protein. If we take a total mitochondrion as about 22% protein, the average concentration of the cytochrome would be 0.06 mM. Since all the cytochromes are concentrated in the inner membranes, which may account for 10% or less of the volume of the mitochondrion, the concentration of cytochromes may approach 1 mM in these membranes. This is sufficient to ensure rapid reactions with substrates. 

Baker s yeast contains at least four lactate dehydrogenases, three of which are located in the mitochondrion and one in the cytoplasm (Table 1). Electron flow in the mitochondrial enzymes is linked to cytochromes rather than nicotinamides. Their apparent physiological function is the reversible interconversion of pyruvate and lactate, and it is not clear whether any of these four enzymes accept ketones other than pyruvate, which would limit their importance in organic synthesis. 

Degree of Reduction of Electron Carriers in the Respiratory Chain The degree of reduction of each carrier in the respiratory chain is determined by conditions in the mitochondrion. For example, when NADH and 02 are abundant, the steady-state degree of reduction of the carriers decreases as electrons pass from the substrate to 02. When electron transfer is blocked, the carriers before the block become more reduced and those beyond the block become more oxidized (see Fig. 19-6). For each of the conditions below, predict the state of oxidation of ubiquinone and cytochromes b, clt c, and a + a3. 

Fig. 3. The rate-limiting step of steroidogenesis under ACTH regulation. The transfer of cholesterol (C) from the outer to the inner mitochondrial membrane under ACTH regulation (step 3) makes cholesterol available to cytochrome /M50scc for conversion to pregnenolone (step 4), which diffuses out of the mitochondrion (step 5). Because of its insolubility in aqueous media, cholesterol must be transported to mitochondria, probably by SCP2, from a precursor pool (step 2). Here, cholesterol in the precursor pool is shown as being formed from cholesterol esters (CE) by cholesterol ester hydrolase (CEH) (step 1) other possible pathways are shown in Figs. 4 and 6. From Ref. 14.

Approximately 1000 proteins comprise the mitochondrion the majority are encoded on genes located on nuclear DNA. In fact, as seen in Figure 8-5, the mtDNA encodes only 13 proteins. These mtDNA-encoded proteins are the seven subunits (ND1,2,3,4,4L, 5, and 6) of the NADH-dehydrogenase (RC I) one subunit (cytochrome b) of RC III three subunits (CO I, II, and III) of cytochrome c oxidase (RC IV) and two subunits (A6 and A8) of the ATP synthase (RC V).A11 of these proteins are components of the ETC or the ATP synthase involved in OXPHOS. In addition to these 13 proteincoding genes, the mtDNA encodes 22 mitochondrial transfer ribonucleic acids (tRNAs) and two ribosomal RNA (rRNA) molecules (the large 16S rRNA and the small 12S rRNA). 

Menadione (vitamin K3),phylloquinone (vitamin Kj), and ascorbate (vitamin C) have been used to donate electrons to cytochrome c. For example, ascorbate is oxidized to dehydroascorbate as it uses its electrons to reduce cytochrome c directly. The dehydroascorbate is quickly reduced to ascorbate in the mitochondrion by NADH or FADH2. Menadione appears to improve cellular phosphate metabolism and to enhance electron transfer after a respiratory Complex I block. 

Mitochondria release not only cytochrome c but also many pro-apoptotic factors (Table 17.1). They are normally localized in the intermembrane space of mitochondria. However, except for cytochrome c and the apoptosis inducing factor (AIF), their functions in the mitochondria have not been determined or they may have no function under normal conditions. Because they are larger than 5kD, they remain inside the mitochondrion. Once the mitochondrial outer membrane is permeabi-... 

The control of the respiration process and ATP synthesis shifts as the metabolic state of the mitochondria changes. In an isolated mitochondrion, control over the respiration process in state 4 is mainly due to the proton leak through the mitochondrial inner membrane. This type of control decreases from state 4 to state 3, while the control by the adenine nucleotide and the dicarboxylate carriers, cytochrome oxidase, increases. ATP utilizing reactions and transport activities also increase. Therefore, in state 3, most of the control is due to respiratory chain and substrate transport. 

If you need more haemoglobin for tomorrow—for tomorrow And your cytochromic store s run out of steam—out of steam There s a metabolic pathway you should follow—you should follow Biosynthetic route that leads to haem—leads to haem In mitochondrion the path commences—path commences The d-amino laevulinate way— inate way Glycine decarboxylates when it condenses—it condenses On the synthetase with succinyl Co A. 

Bc1-2/Bc1-Xl proteins are localized on the outer mitochondrial membrane. They are assumed to function as ion channels, maintaining the integrity of the mitochondrion and preventing shedding of cytochrome c. 

All three respiratory complexes are typical integral membrane proteins that span the inner mitochondrial membrane. Each consists of several different subunits, the exact number of which is still under debate. The genes of some subunits of cytochrome oxidase and the />c, complex are in mitochondrial DNA (mtDNA). These proteins are synthesised inside the mitochondrion. However, most proteins of these complexes, as well as cytochrome c, are synthesised on cytoplasmic ribosomes and coded by the nuclear genome. This raises intriguing questions of how the latter are imported into the mitochondrion and inserted into the mitochondrial membrane, as well as of how mitochondrial and cytoplasmic transcription and translation are synchronised [3-5]. 

Mitochondrial cytochrome oxidase (EC 1.9.3.1) consists of three polypeptides synthesised in the mitochondrion, and several others synthesised in the cytoplasm (Table 3.3). Preparations of the mammalian enzyme have been shown to contain up to 13 different polypeptides, and there is uncertainty at present as to which are true constituents of the enzyme. The present opposing views are those of Capaldi et al. [85,96], who regard eight polypeptides as unique constituents, and Kadenbach et al. [93,94], who suggest that all 13 are true parts of the enzyme. 

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