Matrix of mitochondria

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. 

Lambeth, D.O. Mehus, J.G. Ivey, M.A. Milavetz, B.L Characterization and cloning of a nucleoside-diphosphate kinase targeted to matrix of mitochondria in pigeon. J. Biol. Chem., 272, 24604-24611 (1997)... 

Fe- and Mn-containing superoxide dismutases have, moreover, been isolated. They show striking sequence homologies. (Fe)-SOD has mainly been found in prokaryotes. (Mn)-SOD occurs in prokaryotes, (20,000), in the matrix of mitochondria, although encoded by the nucleus, and also in the cytosol of e.g. liver cells (human, chicken in contrast with rat)... 

Matrix of the mitochondrion This gel-like solution in the interior of mitochondria is fifty percent protein. These molecules include the enzymes responsible for the oxidation of pyruvate, amino acids, fatty acids (by p-oxidation), and those of the tricarboxylic acid (TCA) cycle. The synthesis of urea and heme occur partially in the matrix of mitochondria. In addition, the matrix contains NAD+and FAD (the oxidized forms of the two coenzymes that are required as hydrogen acceptors) and ADP and Pj, which are used to produce ATP. [Note The matrix also contains mitochondrial RNA and DNA (mtRNA and mtDNA) and mitochondrial ribosomes.]... 

The formation of carbamoyl phosphate (NH2COOPO3-) takes place in the matrix of mitochondria ... 

The answer is c. (Murray, pp 307—346. Scriver, pp 1909-1964. Sack, pp 121-138. Wilson, pp 287-317.) The steps of the urea cycle are divided between the mitochondrial matrix and cytosol of liver cells in mammals. The formation of ammonia, its reaction with carbon dioxide to produce carbamoyl phosphate, and the conversion to citrulline occur in the matrix of mitochondria. Citrulline diffuses out of the mitochondria, and the next three steps of the cycle, which result in the formation of urea, all take place in the cytosol. Peroxisomes have single membranes, in contrast to the double membranes of mitochondria. They house catalase and enzymes for medium- to long-chain fatty acid oxidation. 

There are four kinds of SODs. In mammalian systems three isozymes are known. Table 1 indicates the general properties of the mammalian isozymes. The fourth enzyme, Fe-SOD, is structurally homologous to Mn-SOD (P3,P4,S14) and is only found in bacteria. Cu,Zn-SOD and extracellular (EC) SOD are located in the cytosol and extracellular fluid, respectively, whereas Mn-SOD is mainly located in the matrix of mitochondria (M5,S13,T9,W5,W6,W9). Cu,Zn-SOD and EC SOD contain Cu and Zn in their molecules, whereas Mn-SOD contains the Mn atom. The Cu,Zn-SOD is sensitive to cyanide and H202, whereas Mn-SOD is resistant to these reagents (F4,W5). The difference in the cyanide sensitivity of the two isozymes makes it possible to distinguish the enzymatic activities of the SODs. 

Urea synthesis, which occurs in hepatocytes, begins with the formation of carbamoyl phosphate in the matrix of mitochondria. The substrates for this reaction, catalyzed by carbamoyl phosphate synthetase I, are NH4 and HCO3. (The nitrogen source for carbamoyl phosphate synthetase II, the enzyme involved in pyrimidine synthesis, is glutamine.)... 

To diminish these threats, nature has created a family of metalloenzymes, the SODs. They catalyze the dismutation of superoxide to dioxygen and hydrogen peroxide (Eqs. (1) and (2)). They are differentiated by the redox-active metal copper (Cu/Zn SOD), manganese (MnSOD), iron (FeSOD), or nickel (NiSOD) superoxide dismutases and fall into three evolutionary families (Fig. 2) (10). The iron and manganese SODs are structurally similar and are found in prokaryotes and in the matrix of mitochondria (near the electron transport chain), respectively. Nickel containing SODs are known in some prokaryotes, whereas Cu/Zn are present in the cytosols of virtually all eukaryotic cells and have an independent evolutionary history. 

Small molecular complexes named ribosomes catalyze and regulate this process of protein synthesis. Mammalian ribosomes consist of ribosomal RNAs (rRNAs) and proteins and can be divided into a large (60S) and a small (40S) subunit. Together these two subunits form an SOS complex, which is responsible for the decoding of mRNAs and the formation of peptide bonds to generate polypeptides. As rRNAs catalyze, this process of peptide bond formation ribosomes are defined as ribozymes [16]. Besides the cytoplasm, ribosomes are also found in the matrix of mitochondria. 

In eukaryotes, oxidative phosphorylation occurs in mitochondria, while photophosphorylation occurs in chloroplasts to produce ATP. Oxidative phosphorylation involves the reduction of O2 to H2O with electrons donated by NADH and FADH2 in all aerobic organisms. After, carbon fuels (nutrients) are oxidized in the citric acid cycle, electrons with electron-motive force is converted into a proton-motive force. Photophosphorylation involves the oxidation of H2O to O2, with NADP as electron acceptor. Therefore, the oxidation and the phosphorylation of ADP are coupled by a proton gradient across the membrane. In both organelles, mitochondria and chloroplast electron transport chains pump protons across a membrane from a low proton concentration region to one of high concentration. The protons flow back from intermembrane to the matrix in mitochondria, and from thylakoid to stroma in chloroplast through ATP synthase to drive the synthesis of adenosine triphosphate. Therefore, the adenosine triphosphate is produced within the matrix of mitochondria and within the stroma of chloroplast. 

Mitochondria Mitochondria are organelles surrounded by two membranes that differ markedly in their protein and lipid composition. The inner membrane and its interior volume, the matrix, contain many important enzymes of energy metabolism. Mitochondria are about the size of bacteria, 1 fim. Cells contain hundreds of mitochondria, which collectively occupy about one-fifth of the cell volume. Mitochondria are the power plants of eukaryotic cells where carbohydrates, fats, and amino acids are oxidized to CO9 and H9O. The energy released is trapped as high-energy phosphate bonds in ATR... 

COMPARTMENTALIZED PYRUVATE CARBOXYLASE DEPENDS ON METABOLITE CONVERSION AND TRANSPORT The second interesting feature of pyruvate carboxylase is that it is found only in the matrix of the mitochondria. By contrast, the next enzyme in the gluconeogenic pathway, PEP carboxykinase, may be localized in the cytosol or in the mitochondria or both. For example, rabbit liver PEP carboxykinase is predominantly mitochondrial, whereas the rat liver enzyme is strictly cytosolic. In human liver, PEP carboxykinase is found both in the cytosol and in the mitochondria. Pyruvate is transported into the mitochondrial matrix, where it can be converted to acetyl-CoA (for use in the TCA cycle) and then to citrate (for fatty acid synthesis see Figure 25.1). /Uternatively, it may be converted directly to 0/ A by pyruvate carboxylase and used in glu-... 

Transport signals can be of the import or the export type. Import signals are contained in proteins that are transported into the individual compartments of mitochondria (matrix, inner membrane, intramembrane compartment, outer membrane), peroxisomes (lumen, boundary membrane) and into the interior 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-... 

Figure 29-9. Reactions and intermediates of urea biosynthesis. The nitrogen-containing groups that contribute to the formation of urea are shaded. Reactions and occur in the matrix of iiver mitochondria and reactions , , and in iiver cytosoi. COj (as bicarbonate), ammonium ion, ornithine, and cit-ruiiine enter the mitochondriai matrix via specific carriers (see heavy dots) present in the inner membrane of iiver mitochondria.

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

Figure 11.6 Schematic representation of Ca2+ transport in and out of mitochondria, showing all the Ca2+ transporters and activation of matrix dehydrogenases. PTP—permeability transition pore. (From Carafoli, 2003. Copyright 2003, with permission from Elsevier.)...

The dtric acid cycle is shown in Figure 1-13-1, All the enzymes are in the matrix of the mitochondria except succinate dehydrogenase, which is in the inner membrane. 

Medium-chain acyl-CoA synthetase, which is present within the mitochondrial matrix of the liver, activates fatty acids containing from four to ten carbon atoms. Medium-chain length fatty acids are obtained mainly from triacylglycerols in dairy products. However, unlike long-chain fatty acids, they are not esterified in the epithelial cells of the intestine but enter the hepatic portal vein as fatty acids to be transported to the liver. Within the liver, they enter the mitochondria directly, where they are converted to acyl-CoA, which can be fully oxidised and/or converted into ketone bodies. The latter are released and can be taken up and oxidised by tissues. 

The tricarboxylic acid cycle not only takes up acetyl CoA from fatty acid degradation, but also supplies the material for the biosynthesis of fatty acids and isoprenoids. Acetyl CoA, which is formed in the matrix space of mitochondria by pyruvate dehydrogenase (see p. 134), is not capable of passing through the inner mitochondrial membrane. The acetyl residue is therefore condensed with oxaloacetate by mitochondrial citrate synthase to form citrate. This then leaves the mitochondria by antiport with malate (right see p. 212). In the cytoplasm, it is cleaved again by ATP-dependent citrate lyase [4] into acetyl-CoA and oxaloacetate. The oxaloacetate formed is reduced by a cytoplasmic malate dehydrogenase to malate [2], which then returns to the mitochondrion via the antiport already mentioned. Alternatively, the malate can be oxidized by malic enzyme" [5], with decarboxylation, to pyruvate. The NADPH+H formed in this process is also used for fatty acid biosynthesis. 

In isosmotlc solutions, movement of neutral amino acids such as prollne across the inner membrane into the matrix results in swelling of mitochondria (20). As shown in Figure 3C, the movement of proline is thought to occur via a uniport. The increased concentration of proline in the matrix produces an osmotic-induced swelling. Kinetics of the swelling response is shown in the 0 (control) trace. Again, quercetin inhibited this response in a concentration-dependent manner. 

The most typical ultrastructural changes in hepatocytes were sharp swelling of mitochondria with pronounced enlightenment of their matrix and reduction of cristae that are important morphological symptoms of their damage (Fig. 22.2). They were accompanied by appearance of mitochondria of odd shapes, horseshoe shaped... 

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