Active transport kinetics

Wilson, F.A. and Dietschy, J.M. (1974). The intestinal unstirred layer—its surface area and effect on active transport kinetics. Biochem. Biophys. Acta. 363 112-126. 

From a thermodynamic and kinetic perspective, there are only three types of membrane transport processes passive diffusion, faeilitated diffusion, and active transport. To be thoroughly appreciated, membrane transport phenomena must be considered in terms of thermodynamics. Some of the important kinetic considerations also will be discussed. 

Depending upon the mechanism that is employed by the organism to accumulate the solute, internalisation fluxes can vary both in direction and order of magnitude. The kinetics of passive transport will be examined in Section 6.1.1. Trace element internalisation via ion channels or carrier-mediated transport, subsequent to the specific binding of a solute to a transport site, will be addressed in Section 6.1.2. Finally, since several substances (e.g. Na+, Ca2+, Zn2+, some sugars and amino acids) can be concentrated in the cell against their electrochemical gradient (active transport systems), the kinetic implications of an active transport mechanism will be examined in Section 6.1.3. Further explanations of the mechanisms themselves can be obtained in Chapters 6 and 7 of this volume [24,245]. 

Characteristically, within certain concentration limits, if a chemical is absorbed by passive diffusion, then the concentration of toxicant in the gut and the rate of absorption are linearly related. However, if absorption is mediated by active transport, the relationship between concentration and rate of absorption conforms to Michaelis-Menten kinetics and a Lineweaver-Burk plot (i.e., reciprocal of rate of absorption plotted against reciprocal of concentration), which graphs as a straight line. 

Major developments in transport kinetics followed from the work of Gardos who, in 1954, succeeded in restoring K+ uptake in red cell ghosts if ATP was added to the medium. Hoffman (1962) showed that in the presence of inosine, the ghosts extruded Na+. Three components of efflux were distinguished active transport, passive transport, and... 

In cases where the depuration of HOCs from BMOs involves enzyme-mediated biotransformations (Eq. 7.4) or active transport mechanisms, and environmental concentrations are high (e.g. near a point source), depuration rates have been shown to follow Michaelis-Menten kinetics (Spade and Hamelink, 1985). Michaelis-Menten kinetics is elicited when an enzyme or active transport system is saturated with a chemical. This type of kinetics is characterized by lower values of keS at sites with high HOC concentrations. If k s are unchanged at high concentration sites, Michaelis-Menten kinetics will result in elevated BAFs. However, if chemical concentrations become toxic, finfish likely avoid the area and sessile organisms such as mussels may close their valves for extended periods (Huckins et al., 2004). 

The transport mechanisms that operate in distribution and elimination processes of drugs, drug-carrier conjugates and pro-drugs include convective transport (for example, by blood flow), passive diffusion, facilitated diffusion and active transport by carrier proteins, and, in the case of macromolecules, endocytosis. The kinetics of the particular transport processes depend on the mechanism involved. For example, convective transport is governed by fluid flow and passive diffusion is governed by the concentration gradient, whereas facilitated diffusion, active transport and endocytosis obey saturable MichaeUs-Menten kinetics. 

Carrier-mediated passage of a molecular entity across a membrane (or other barrier). Facilitated transport follows saturation kinetics ie, the rate of transport at elevated concentrations of the transportable substrate reaches a maximum that reflects the concentration of carriers/transporters. In this respect, the kinetics resemble the Michaelis-Menten behavior of enzyme-catalyzed reactions. Facilitated diffusion systems are often stereo-specific, and they are subject to competitive inhibition. Facilitated transport systems are also distinguished from active transport systems which work against a concentration barrier and require a source of free energy. Simple diffusion often occurs in parallel to facilitated diffusion, and one must correct facilitated transport for the basal rate. This is usually evident when a plot of transport rate versus substrate concentration reaches a limiting nonzero rate at saturating substrate While the term passive transport has been used synonymously with facilitated transport, others have suggested that this term may be confused with or mistaken for simple diffusion. See Membrane Transport Kinetics... 

The model active transport system described by Dr. Thomas is based on an asymmetric arrangement of two enzymes. A model active transport system was also described by Blumenthal et al. several years ago based on a single enzyme immobilized between asymmetric boundaries [Blumenthal, Caplan, and Kedem, Biophys. J., 7, 735 (1967)]. In the latter case the phenomenological coefficients were measured, and it was possible to demonstrate Onsager symmetry and the correlation between the thermodynamic coefficients and the kinetic constants. 

Transport is a three-phase process, whereas homogeneous chemical and phase-transfer [2.87, 2.88] catalyses are single phase and two-phase respectively. Carrier design is the major feature of the organic chemistry of membrane transport since the carrier determines the nature of the substrate, the physico-chemical features (rate, selectivity) and the type of process (facilitated diffusion, coupling to gradients and flows of other species, active transport). Since they may in principle be modified at will, synthetic carriers offer the possibility to monitor the transport process via the structure of the ligand and to analyse the effect of various structural units on the thermodynamic and kinetic parameters that determine transport rates and selectivity. 

In view of the substantial requirement of bacteria for Mg2+, it is not surprising that selective, active transport processes are available for its uptake.178 The bacterium E. coli has two kinetically... 

This mechanism is important for compounds that lack sufficient lipid solubility to move rapidly across the membrane by simple diffusion. A membrane-associated protein is usually involved, specificity, competitive inhibition, and the saturation phenomenon and their kinetics are best described by Michaelis-Menton enzyme kinetic models. Membrane penetration by this mechanism is more rapid than simple diffusion and, in the case of active transport, may proceed beyond the point where concentrations are equal on both... 

Batchelor M, Schenk JO (1998) Protein kinase A activity may kinetically upregulate the striatal transporter for dopamine. J Neurosci 18 10304-9 Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg s Arch Pharmacol 317 36 13 Bean AJ, During MJ, Roth RH (1990) Effects of dopamine autoreceptor stimulation on the release of colocalized transmitters in vivo release of dopamine and neurotensin from rat prefrontal cortex. Neurosci Lett 108 143-8... 

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