Competition for Transport

Second, certain nucleotide phosphonates (e.g., adefovir and cidofovir) are effective antivirals, but their use in the clinic is limited by renal toxicity. This is believed to be caused by avid uptake at the basolateral membrane of renal proximal tubule cells followed by slow transport into the urine at the apical membrane, a sequence of events that results in intracellular drug accumulation and thus toxicity. As with penicillin, the OAT family of transporters has been implicated in cidofovir uptake. Co-administration of probenecid with cidofovir has been shown to decrease renal clearance of the antiviral and reduce its nephrotoxicity, presumably through com- 

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Most commonly influenced by chemical and physical interactions between the toxicant and components of the medium. Complexation of metals or binding of organic substances can influence exposure of the organism. Can also be mediated by interactions between the matrix and the physiology and biochemistry of the organism, such as in competition for transport sites. 

If hybrids and diesels are the toughest competition for transportation fuel cells, then cellulosic ethanol is probably the tough-... 

For transporters, relatively low protein expression level and limited transport capacity makes for nonlinear, enzyme-like transport kinetics that is, the transport rate saturates with increasing substrate concentration. This phenomenon is the basis for the competitive interactions generally found for chemicals that are handled by one or more common transporters this is usually manifest as inhibition of the transport of one chemical by a structural analog. The extent to which these competitive interactions are important depends on the concentrations of the chemicals involved, their relative affinities for the common transporter, and their phar-macological/toxicological profiles (effects, effective concentrations, therapeutic index). Competition for transport is discussed below in the context of drug-drug interactions. 

Competition for Transport on a Circulating Carrier-Protein (J). Once across the serosal border, zinc must still be bound by a transport protein to carry It through the portal circulation, away from the Intestine. There Is debate as to whether this role Is played by transferrin (11) or by albumin (12,13). In either case, the presence of excess metal(s) that bind to the same site on the portal transport protein as zinc would Impede the passage of zinc Into the systemic circulation. 

Facilitated diffusion is very similar to passive diffusion with the difference that transfer across membranes is assisted by the participation of carrier proteins embedded in the membrane bilayer. Again, the direction of passage will be from the side of the membrane with high concentration of a chemical to the side with low concentration this also occurs without energy expenditure by the cell. Such a process is somewhat specific in the sense that it applies to molecules that are able to bind to a carrier protein. Absorption of nutrients such as glucose and amino acids across the epithelial membrane of the gastrointestinal tract occurs by facilitated diffusion. Since a finite number of carriers are available for transport, the process is saturable at high concentrations of the transported molecules and competition for transport may occur between molecules of similar structure. 

Altered excretion Competition for transport systems in kidney Elimination of methotrexate (cancer chemotherapy) inhibited by probenecid (for gout)... 

Probenecid acts at the luminal side of the renal tubular cell. Thus, it must use the organic acid secretory system to enter the lumen of the tubule, because it is not filtered. Drugs such as aspirin and isoniazid (as well as most (3-lactam antibiotics, and a host of other drugs that are organic acids) also use the organic acid secretory system for transport into the nephron, in their elimination. Thus, there is competition for transport, which may result in a decrease in drug elimination and subsequent increase in plasma levels of the concurrent drug, as well as a decrease in the efficacy of probenecid. 

Some relations between the flux of amino acid and other metabolic events have been demonstrated and also competition for transport between various amino acids has been observed. This suggests that there is a common step involved in the uptake mechanism for amino acids. Competition studies have shown the existence of several specific sites that control the entrance into the cell of various classes of amino acids. These studies have also shown that one generally deals with a saturation phenomenon obeying the Michaelis-Menten kinetics. 

Though specific transporters solely for Cd have not been found yet and are rather unlikely to exist, many transporters with similar affinities for Zn and Cd have been characterized (reviewed by Clemens [18,19]). Cd may enter the plant also via calcium channels [20]. Addition of Ca to the nutrient solution reduces Cd translocation into the shoots while increasing Cd accumulation in the roots [21], indicating a Ca-Cd competition for transport charmels at the xylem loading step of nutrient uptake in the roots. While Cd hyperaccumulators actively enrich Cd in their tissues (see Chapter 12 [22]), most other plants suffer from Cd phytotoxicity. 

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