[Pathophysiology of hypertension. c. Electron transport. 1) Biological transport in the kidney].
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The simplest biological transport system so far extensively investigated is that of monosaccharides in human erythrocytes. Despite its simplicity there is still considerable doubt and divergence of opinion concerning its mechanism. Some confusion may arise as a result of the comparison of diverse data obtained by different workers using a variety of experimental techniques. To minimize this problem, an attempt is made here to repeat, under standard conditions and with as much care as possible, five of the more definitive types of experiments previously performed on this system. It is hoped that the result of this effort is an internally consistent set of data with which the quantitative predictions of various proposed mechanisms may be compared as a primary criterion for their acceptability.
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It is shown by thermodynamic arguments and by semiquantitative considerations that the contribution of thermal migration to biological transport is likely to be small.
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Biological systems are known to be highly transparent to 700- to 1,100-nm near-infrared (NIR) light. It is shown here that the strong optical absorbance of single-walled carbon nanotubes (SWNTs) in this special spectral window, an intrinsic property of SWNTs, can be used for optical stimulation of nanotubes inside living cells to afford multifunctional nanotube biological transporters. For oligonucleotides transported inside living cells by nanotubes, the oligos can translocate into cell nucleus upon endosomal rupture triggered by NIR laser pulses. Continuous NIR radiation can cause cell death because of excessive local heating of SWNT in vitro. Selective cancer cell destruction can be achieved by functionalization of SWNT with a folate moiety, selective internalization of SWNTs inside cells labeled with folate receptor tumor markers, and NIR-triggered cell death, without harming receptor-free normal cells. Thus, the transporting capabilities of carbon nanotubes combined with suitable functionalization chemistry and their intrinsic optical properties can lead to new classes of novel nanomaterials for drug delivery and cancer therapy.
We discuss the generic time behavior of reaction-diffusion processes capable of modeling various types of biological transport processes, such as ligand migration in proteins and gating fluctuations in ion channel proteins. The main observable in these two cases, the fraction of unbound ligands and the probability of finding the channel in the closed state, respectively, exhibits an algebraic t-1/2 decay at intermediate times, followed by an exponential cutoff. We provide a simple framework for understanding these observations and explain their ubiquity by showing that these qualitative results are independent of space dimension. We also derive an experimental criterion to distinguish between a one-dimensional process and one whose effective dimension is higher.
A thermodynamically constrained method of flux ratio analysis, based upon a previously developed thermodynamic rate ratio equation has been developed. In this paper it is demonstrated that, for a complex reaction, application of the thermodynamic rate ratio equation may provide a useful tool for the interpretation of unidirectional flux data thought to be mediated by the reaction, provided that: (i) a clearly defined mechanism for the reaction has been proposed; (ii) a set of partial reaction components may be defined for the reaction from the proposed mechanism, with the rate ratio of at least one of these components being amenable to experimental measurement. This paper defines the conditions for which the rate ratio of a component reaction may be measured, and illustrates the basic principles underlying this approach to flux ratio analysis by direct application to a number of hypothetical mechanisms for biological transport phenomena.
A novel method for defining the steady-state unidirectional rates of complex reactions has previously been developed (Wagg, 1988 Ph.D. Thesis, Monash University, Australia). This methodology is based upon the method of Wagg (1987, J. theor. Biol. 128, 375-385) for defining the steady-state unidirectional fluxes of chemical species through branched chemical, osmotic and chemiosmotic reactions. It offers a number of distinct advantages over existing approaches to steady-state rate analysis: it is relatively simple to apply to complex reactions and is readily amenable to computer-based application. The method is demonstrated by direct application to a number of hypothetical models for biological transport phenomena.
Kinetic equations are derived for reversible inhibition of both active and facilitated transport systems for seven common experimental arrangements. It is shown that the unique features of transport kinetics may be exploited to give new kinds of information. It is also shown that that the familiar rules of enzyme kinetics, though often applied to transport, can be seriously misleading. The analysis leads to the following general conclusions: (1) A competitive mechanism frequently gives rise to non-competitive kinetics, depending on the experimental design, but a non-competitive mechanism never produces competitive kinetics. (2) Inhibition studies on exchange diffusion at equilibrium in non-active systems or in the final steady state in active systems are the only unambiguous kinetic tests to distinguish competitive from non-competitive mechanisms. (3) Substrate analogs that are bound to the carrier and transported are readily distinguished by inhibition kinetics from those not transported, even though both may rapidly enter the cell by another route. (4) Even in non-active systems competitive inhibitors commonly have far different affinities for the substrate sites on the two membranes faces: where sufficient non-polarity allows their penetration into the cell, inhibition kinetics readily establish such sideness in their action. (5) Inhibition kinetics of the mixed competitive and non-competitive type result from moderately asymmetrical binding of inhibitor at the substrate site. (6) Asymmetry is a necessary feature of active transport: hence studies of inhibition kinetics should provide important insights into its mechanism.