Mitochondrial membrane exchange across

The resistance of cells to lysis by antibodies and complement can be removed by treating the cells with neuraminidase. Glycoproteins have been shown to participate in binding Ca + ions to, and in transporting Ca + ions across, mitochondrial membranes. Removal of sialic acid residues from the surface of cultured heart cells increased the ability of the cells to exchange Ca " ions, but that of K+ ions was unaffected. Glycoproteins on the surface of human KB cells are involved in binding adenovirus. ... 

SELvrrN, M. J., A. P. Dawson, M. Stockdale, and R. Cains Chloridehydroxide exchange across mitochondrial, erythrocyte and artificial hpid membranes mediated by trialkyl- and triphenyltin compoimds. Eur. J. Biochem. 14, 120 (1970). 

Because the inner mitochondrial membrane is impermeable to protons and other ions, special exchange transporters span the membrane to allow passage of ions such as OH, Pf, ATP , ADP, and metabo-htes, without discharging the electrochemical gradient across the membrane. 

Examples of such intra cellular membrane transport mechanisms include the transfer of pyruvate, the symport (exchange) mechanism of ADP and ATP and the malate-oxaloacetate shuttle, all of which operate across the mitochondrial membranes. Compartmentalization also allows the physical separation of metabolically opposed pathways. For example, in eukaryotes, the synthesis of fatty acids (anabolic) occurs in the cytosol whilst [3 oxidation (catabolic) occurs within the mitochondria. 

The transport systems of the inner mitochondrial membrane use various mechanisms. Metabolites or ions can be transported alone (uniport, U), together with a second substance (symport, S), or in exchange for another molecule (antiport. A). Active transport—i. e., transport coupled to ATP hydrolysis—does not play an important role in mitochondria. The driving force is usually the proton gradient across the inner membrane (blue star) or the general membrane potential (red star see p. 126). 

It is very difficult to measure the flux of protons across the membrane either out of the mitochondria into the cytoplasm or from the cytoplasm through the ATP synthase into the mitochondria. Therefore, estimates of the stoichiometry have often been indirect. One argument is based on thermodynamics. If Ap attains values no more negative than -160 mV and Rp within mitochondria reaches at least 104 M 1, we must couple AGh of -15.4 kj/ mol to AG of formation of ATP of +57.3 kj/ mol. To do this four H+ must be translocated per ATP formed. Recent experimental measurements with chloroplast ATP synthase188 also favor four H+. It is often proposed that one of these protons is used to pump ADP into the mitochondria via the ATP-ADP exchange carrier (Section D). Furthermore, if Rp reaches 106 M 1 in the cytoplasm, it must exceed 104 M 1 in the mitochondrial matrix. 

Carnitine acyltransferase I, which is located on the outer mitochondrial membrane, transfers the fatty acyl group from fatty acyl-CoA to the hydroxyl (OH) group of carnitine. The acyl-carnitine then moves across the intermembrane space to a translocase enzyme, which, in turn, moves the acyl-carnitine to carnitine acyltransferase II, which exchanges the carnitine for Coenzyme A. 

Acylcamitine then moves across the mitochondrial membrane via an antiport, which also transports carnitine in the opposite direction. In the mitochondria, carnitine is once more exchanged with CoA, which is a reversal of Equation (19.6), yielding acyl-CoA. Free carnitine is then returned to the extramitochondrial space by the antiport. The carnitine shuttle is shown in Figure 19.5. Carnitine is synthesized in the organism from lysine. The symptoms of carnitine deficiency are muscle weakness, cardiac myopathy, and hypertriglyceridemia. These are observed in certain genetic disorders, alcoholism, hemo-... 

Citrulline is exchanged for ornithine across the inner mitochondrial membrane by ORNT-1. Ornithine is produced in the cytosol as the final step in the urea cycle and must be returned to the mitochondrial matrix for transcarbamoyla-tion by OTC. A second ornithine-citrulline antiporter (ORNT-2) is also expressed in the liver mitochondria and may attenuate the severity of disease in patients with HHH (Hyperammonemia, Hyperornithinemia, Homocitrullinuria) disease due to ORNT-1 deficiency. This disorder typically manifests later in life with intermittent hyperammonemic encephalopathy and protein aversion. Intramitochondrial ornithine deficiency causes both hyperammonemia and hyperornithinemia due to a lack of substrate for OTC. Homocitrullinuria occurs due to the use of lysine by OTC as an alternate substrate. The diagnosis is confirmed by mutation analysis. 

Translocation systems of the inner mitochondrial membrane are listed in Table 14-5. Anion translocators are responsible for electroneutral movement of dicarboxylates, tricarboxylates, a-ketoglutarate, glutamate, pyruvate, and inorganic phosphate. Specific electrogenic translocator systems exchange ATP for ADP, and glutamate for aspartate, across the membrane. The metabolic function of the translocators is to provide appropriate substrates (e.g., pyruvate and fatty acids) for mitochondrial oxidation that is coupled to ATP synthesis from ADP and Pj. 

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