Translocators kinetic properties

Finally for effects where both the translocation and kinetic properties are important one can merge both models. This can be done by including the transport corrections in the kinetic model described here. In this case different transport rate functions result in different influx coefficients and, hence, different kinetic properties of the proteasome. This modeling approach is especially important for the... 

In this account we will review the structural and functional properties of the respiratory chain components, as they are known from studies with intact mitochondria, vesicles of the inner mitochondrial membrane (submitochondrial particles), or isolated complexes. The latter may additionally be reconstituted into liposomal membranes. To some extent we will also review the knowledge on the integrated functions of the respiratory chain with main emphasis on proton translocation and essential thermodynamic and kinetic properties. 

For most mitochondrial transport systems inhibitors are available and these have been very useful in studies with isolated mitochondria, not only in the study of their kinetic properties but also for the isolation of some of the translocator proteins. In addition, some of the inhibitors can be used in studying the role of mitochondrial transport systems in metabolic processes as they occur in the intact cell. Fig. 1 gives a list of inhibitors commonly used. For a more complete list the reader is referred to [2,3,5-7]. 

It must be realised that the kinetic properties of the translocators may vary from species to species and even from tissue to tissue in the same species. One example is the relatively high capacity of the tricarboxylate translocator in liver compared to that in heart [1,19], which is related to the absence of extramitochondrial fatty, acid synthesis in heart. Another example is the high activity of the dicarboxylate translocator in liver compared to that in heart [19] which is related to the absence of gluconeogenesis in heart. 

An important question is whether mitochondrial pyruvate transport can regulate pyruvate metabolism. One way to approach this problem is to carry out careful titrations of pyruvate-dependent processes with the transport inhibitors. So far, such experiments have not been done. Inspection of the kinetic properties of the pyruvate translocator, however, shows that limitation of pyruvate metabolism by its transport into the mitochondria is possible. For liver the average reported is 70 nmol/min/mg mitochondrial protein, which is 900 jumol/g dry weight of liver tissue/h (Table 1). The maximum rate of glucose synthesis from lactate in hepato-cytes is about 430 jumol/g dry weight/h [86], so that flux through the pyruvate translocator under these conditions is 2 X 430 = 860 jumol/g dry weight/h, which is close to its In the presence of lactate plus ethanol mitochondrial pyruvate... 

Characterize the translocator (kinetics, regulation, cofactors, electrical properties)... 

The mapping of the time-evolution equation for the translocation kinetics to the Fokker-Planck equation allows immediate deduction of the various properties of polymer translocation, directly from the equations presented in Chapter 6. The inputs in obtaining the results are the free energy landscapes derived in Chapter 5 and the diffusion constants km. We give below the key results for polymer translocation by copying the general solutions presented in Chapter 6. We shall take the diffusion coefficient of the monomer km to be uniform (ko) in the following sections. 

Most of the early work on membranes was based on experiments with erythrocytes. These cells were first described by Swammerdam in 1658 with a more detailed account being given by van Leeuwenhoek (1673). The existence of a cell (plasma) membrane with properties distinct from those of protoplasm followed from the work of Hamburger (1898) who showed that when placed in an isotonic solution of sodium chloride, erythrocytes behaved as osmometers with a semipermeable membrane. Hemolysis became a convenient indication of the penetration of solutes and water into the cell. From 1900 until the early 1960s studies on cell membranes fell into two main categories increasingly sophisticated kinetic analyses of solute translocation, and rather less satisfactory examinations of membrane composition and organization. 

The use of nanoparticles for oral appHca-tion is an intensively studied concept for the delivery of poorly soluble drugs, as discussed above. Particle uptake has been known for more than 50 years via M-cells as specialized phagocytic enterocytes, but also via lymphoid tissue and normal intestinal enterocytes [75, 76]. The kinetics of particle uptake and translocation depend on biopharmaceutical parameters like accessibility through the mucus and contact with the enterocytes, as well as on the physical properties of the particle like its size, particle charge, surfactant coating and, sometimes, targeting devices. 

Ohta S, Tsuboi M, Yoshida M and Kagawa Y (1980) Inter subunit interaction in proton translocating adenosine triphosphatase as revealed by hydrogen exchange kinetics. Biochemistry 19t 2160-2164. Pullman ME and Monroy GC (1963) A naturally occuring inhibitor of mitochondrial adenosine triphosphtase, J. Biol. Chem. 238, 3762-3769. Rott R and Nelson N (1981) Purification and immunological properties of proton ATPase complexes from yeast and rat liver mitochondria, J. Biol. Chem. 256, 9224-9228. 

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