Transport processes mediated

I. values ranged between 1 and 20 mM. The compounds did not act as uncouplers or directly inhibit ATP synthesis. However, naringenln, some of the flavones, and the clnnamates acids inhibited th hydrolysis of ATP catalyzed by mitochondrial Mg -ATPase. The Inhibition of substrate oxidation appears to result from alterations and perturbations induced in the inner membrane as evidenced by Interference with carrier-mediated transport processes. 

Transport systems. Partitioning of various types of molecules such as allelochemlcals into the lipid bilayer of the mitochondrial inner membrane can perturb the membrane and alter the conformation, properties, and function of components of the membranes. Unfortunately, it is not always possible to demonstrate directly the existence of carrier systems, but indirect evidence can be obtained. Alterations induced to the membrane are sometimes reflected in the osmotic behavior of mitochondria. The inner membrane is relatively impermeable to many cations, including K and H, and many solutes (31). Hence, the organelles are osmotic-ally stable under certain conditions. Indications were obtained that the allelochemlcals inhibited the action of carrier-mediated transport processes associated with the mitochondrial inner membrane (as reflected in the osmotic behavior). Responses obtained with quercetin are shown in Figure 3. Mitochondria are osmotically... 

K0 is now the zero-order rate constant and is expressed in terms of mass/time. In an active carrier-mediated transport process following zero-order kinetics, the rate of drug transport is always equal to K once the system is fully loaded or saturated. At subsaturation levels, the rate is initially first order as the carriers become loaded with the toxicant, but at concentrations normally encountered in pharmacokinetics, the rate becomes constant. Thus, as dose increases, the rate of transport does not increase in proportion to dose as it does with the fractional rate constant seen in first-order process. This is illustrated in the Table 6.1 where it is assumed that the first-order rate constant is 0.1 (10% per minute) and the zero-order rate is 10 mg/min. 

Nephrotoxicity Retention of the aminoglycosides by the proximal tubular cells disrupts calcium-mediated transport processes and results in kidney damage ranging from mild renal impairment to severe acute tubular necrosis which can be irreversible. 

Fig. 4 Hypothetical carrier-mediated transport process. (From Ref. l)...

The mechanism of the action of lithium on H2O transport lies at some point along the arginine vasopressin-mediated transport process, either before or beyond the formation of cyclic adenosine monophosphate. Forrest et al. [51] suggested that lithium inter-... 

Kinetics of carrier-mediated transport processes is similar to enzyme-substrate reactions and can be described by the Michaelis-Menten equation (Eq. (9.2)), assuming that each transport system has one specific binding site for its substrates. Maximum transport velocity (Vmax) is reached when all binding sites of the respective carrier proteins are occupied by substrate molecules. Substrate turnover can be delineated by the Michaelis constant Km corresponding to the substrate concentration [S], at which half-maximum transport velocity has been reached (Figure 9.5). Km also depends on pH and temperature. In cotransport systems transferring several substrates, the transport protein has a characteristic Km for each molecule transported. 

Bile acids, which have been taken up by the liver, are transported across the hepatocyte and secreted into the bile canaliculus. Newly synthesized bile acids, in a small amount just sufftcient to balance the fraction lost by fecal excretion, join recycled bile acids for biliary secretion. Intracellular bile acid transport may be mediated by carrier proteins (B24, S42). The detailed mechanism of biliary secretion of bile acids and other organic anions into the bile canaliculus is not yet clear (B24). Possible mechanisms include vectorial vesicular transport, fticilitated diflusion, or an energy-requiring carrier-mediated transport process (B24). 

Nearly all enzymes follow what is known as Michaelis-Menten kinetics, which was encountered in Section 10.2.2 for carrier-mediated transport processes. The Michaelis-Menten equation for the rate of metabolism f mei) c.an be written as... 

Little is known about the transport of amino acids across the intestine of nematodes. In vitro studies using isolated segments of intestine from A. suum indicate that uptake of methionine, glycine, histidine and valine is stereospecific and non-linear with respect to concentration, indicative of a mediated transport process (12). Most nematodes excrete a wide range of amino acids (149), and though some of these, such as alanine and proline, are true metabolic end-products, others must be derived from ingested materials. 

The absorption of dietary zinc occurs over the duodenal and jejunal regions of the gastrointestinal tract, and mainly follows via a saturable carrier-mediated transport process (Zapsalis and Beck 1985, Lee et al. 1989). The mechanism and control of zinc absorption from the intestine has not yet been fully elucidated, although absorption of zinc is known to be regulated homeostatically, mainly under the control of pancreatic and intestinal secretion and fecal excretion. Homeostasis may involve metal-binding proteins such as metallothionein and cysteine-rich intestinal protein. Metallothionein plays an essential role in the regulation of zinc metabolism (Richard and Cousins 1975, Petering and Fowler 1986). Other unknown mechanisms may also exist, and the uptake from intestinal mucosa may involve both active and passive transport processes. 

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