Mitochondria and oxidative

Central core disease (CCD) is an autosomal dominant, non-progressive myopathy characterized by hypotonia and proximal muscle weakness in infancy. CCD is named after detection of characteristic central cores that lack both mitochondria and oxidative enzyme... 

The electron transport chain gets its substrates from the NADH and FADH2 supplied by the TCA cycle. Since the TCA cycle and electron transport are both mitochondrial, the NADH generated by the TCA cycle can feed directly into oxidative phosphorylation. NADH that is generated outside the mitochondria (for example, in aerobic glycolysis) is not transported directly into the mitochondria and oxidized—that would be too easy. 

In elderly people, where ageing has resulted in loss of mitochondria and oxidative capacity in the muscles. 

Oxidation of fatty acids occurs in three well-defined steps namely, activation, transport into mitochondria, and oxidation to acetyl-CoA. 

In sum, it is apparent that mitochondria and oxidative stress are closely related and together, through different pathways, contribute to the neurodegenerative... 

J. Lee, S. Giordano, and J. Zhang, Autophagy, mitochondria and oxidative stress crosstalk and redox signalling. Biochem. J., 441 (2012) 523-40. 

MoUer, I.M. (2001). Plant mitochondria and oxidatives tress. Electron transport, NADPH turnover and metabohsm of reactive oxygen species. Annual Review of Plant Physiology and Plant Molecular Biology, 52, 561-591. 

I realize that I will have to skip the chapter on the mitochondria and oxidative phosphorylation which has been developed to such a high degree by Packer and others. This chapter is well known to everybody. Its further interpretation may have been facilitated by the finding that the bacterial membrane (inner membrane) functions in many ways like the mitochondrial membrane and that it can perform active transport. Mitchell s electrochemical model of oxidative phosphorylation has been greatly strengthened by studies on active transport of nutrients in bacterial strains, some of which have defective membrane ATPases. Heppel and his coworkers have provided us with some important guidelines based on experiments carried out by themselves as well as by other laboratories. 

Moller IM. 2001. Plant mitochondria and oxidative stress electron transport, NADPH turnover, and metabolism of reactive oxygen species. Anrm Rev Plant Physiol Plant Mol Biol 52 561-591. 

M. F. Beal. Mitochondria and oxidative damage in amyotrophic lateral sclerosis. FunctNeurol. 16 (4 Suppl) 161-169,2001. 

Finally, citrate can be exported from the mitochondria and then broken down by ATP-citrate lyase to yield oxaloacetate and acetyl-CoA, a precursor of fatty acids (Figure 20.23). Oxaloacetate produced in this reaction is rapidly reduced to malate, which can then be processed in either of two ways it may be transported into mitochondria, where it is reoxidized to oxaloacetate, or it may be oxidatively decarboxylated to pyruvate by malic enzyme, with subse-... 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

Several additional points should be made. First, although oxygen esters usually have lower group-transfer potentials than thiol esters, the O—acyl bonds in acylcarnitines have high group-transfer potentials, and the transesterification reactions mediated by the acyl transferases have equilibrium constants close to 1. Second, note that eukaryotic cells maintain separate pools of CoA in the mitochondria and in the cytosol. The cytosolic pool is utilized principally in fatty acid biosynthesis (Chapter 25), and the mitochondrial pool is important in the oxidation of fatty acids and pyruvate, as well as some amino acids. 

The fatty acids released on triacylglycerol hydrolysis are transported to mitochondria and degraded to acetyl CoA, while the glycerol is carried to the liver for further metabolism. In the liver, glycerol is first phosphorylated by reaction with ATP. Oxidation by NAD+ then yields dihydroxyacetone phosphate (DHAP), which enters the carbohydrate metabolic pathway. We ll discuss this carbohydrate pathway in more detail in Section 29.5. 

Skeletal muscle contains three types of fiber fast-twitch oxidative glycolytic (type 2A), fast-twitch glycolytic (type 2B), and slow-rwitch oxidative fibers (type 1). The proportion of each fiber type varies in different muscles. Different fiber types contain different isoforms of myosin, although there is no evidence that their mitochondria differ qualitatively. It has been reported that there are differences between subsarcolemmal mitochondria and those deeper in the same fiber but this has been questioned (see Sherratt et al., 1988 for references). 

If the glycolytic flux is slow much of the pyruvate formed enters the mitochondria and is oxidized by the citrate cycle and reducing equivalents (2H) from NADH are oxidized indirectly (see below). When the flux is fast there is net production of... 

The metabolism of amino acids is complex and is described in standard text books. These are usually converted by aminotransferases to the corresponding 2-oxoacids which are partly oxidized in the matrix of muscle mitochondria and partly exported to the liver. Glutamate and aspartate yield 2-oxoglutarate and oxaloacetate, respectively, which enter the citrate cycle directly, and other 2-... 

Rieske proteins are constituents of the be complexes that are hydro-quinone-oxidizing multisubunit membrane proteins. All be complexes, that is, bci complexes in mitochondria and bacteria, b f complexes in chloroplasts, and corresponding complexes in menaquinone-oxidizing bacteria, contain three subunits cytochrome b (cytochrome 6e in b f complexes), cytochrome Ci (cytochrome f in b(,f complexes), and the Rieske iron sulfur protein. Cytochrome 6 is a membrane protein, whereas the Rieske protein, cytochrome Ci, and cytochrome f consist of water-soluble catalytic domains that are bound to cytochrome b through a membrane anchor. In Rieske proteins, the membrane anchor can be identified as an N-terminal hydrophobic sequence (13). 

The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) and reduce coenzymes that upon reoxidation are linked to the formation of ATP. 

The reduced coenzymes are oxidized by the respiratory chain linked to formation of ATP. Thus, the cycle is the major route for the generation of ATP and is located in the matrix of mitochondria adjacent to the enzymes of the respiratory chain and oxidative phosphorylation. 

Erythrocytes Transport of O2 1 Glycolysis, pentose phosphate pathway. No mitochondria and therefore no p-oxidation or citric acid cycle. Glucose Lactate 1 (Hemoglobin) ... 

MAO is bound to the outer membrane of mitochondria and is responsible for the oxidative deamination of noradrenaline. There are two isoforms of this enzyme, MAO-A... 

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

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