Specialized transport processes

Lipid-soluble substances traverse the membrane by dissolving in the lipoid phase, and the lipid-insoluble substances penetrate only when they are small enough to pass through the pores. The absorption of large lipid-insoluble substances such as sugars and amino acids is accomplished by specialized transport processes. 

The cell body contains the nucleus and is the site of synthesis of virtually all neuronal proteins and membranes. Some proteins are synthesized in dendrites, but none are made In axons or axon terminals. Special transport processes Involving microtubules move proteins and membranes from their sites of synthesis in the cell body down the length of the axon to the terminals (Chapter 20). 

Figure 7.4 Mechanisms of drug flux across a polarized monolayer including passive diffusion, carrier mediated processes and specialized transport processes.

The axons of neurons appear to have special transport processes for moving molecules into and out of the cell body (soma). The presence of special transport mechanisms in these cells is essential for their function, since neurons vary greatly in size, with some extending over 1 m, while protein synthesis occurs predominantly in the soma. Transport rates for different solutes occur in two categories slow (1-lOmm/day) and fast (100-400mm/day), and occur in the anterograde (away from the cell body) and retrograde (toward the cell body) directions. The speed of the slow processes is consistent with rates of diffusion, but the fast processes require additional mechanisms [9, 128]. 

When a specialized transport process is involved, this may be characterized by performing a sequence of studies at different constant levels of non-tracer mother substance while determining the transport rate for tracer, which has a linear transport at each one of these constant levels. The linear transport rate, PS, is influenced by the concentration of the mother substance in a particular way, namely that there is competition between the non-tracer and tracer substances for transport a high concentration of non-tracer mother substance reduced the value of PSp. obtained via the modeling analysis (Bassingthwaighte, 1982),... 

Ceramic, Metal, and Liquid Membranes. The discussion so far implies that membrane materials are organic polymers and, in fact, the vast majority of membranes used commercially are polymer based. However, interest in membranes formed from less conventional materials has increased. Ceramic membranes, a special class of microporous membranes, are being used in ultrafHtration and microfiltration appHcations, for which solvent resistance and thermal stabHity are required. Dense metal membranes, particularly palladium membranes, are being considered for the separation of hydrogen from gas mixtures, and supported or emulsified Hquid films are being developed for coupled and facHitated transport processes. 

The ABC-transporter superfamily represents a large group of transmembrane proteins. Members of this family are mainly involved in ATP-dependent transport processes across cellular membranes. These proteins are of special interest from a pharmacological point of... 

Since many essential nutrients (e.g., monosaccharides, amino acids, and vitamins) are water-soluble, they have low oil/water partition coefficients, which would suggest poor absorption from the GIT. However, to ensure adequate uptake of these materials from food, the intestine has developed specialized absorption mechanisms that depend on membrane participation and require the compound to have a specific chemical structure. Since these processes are discussed in Chapter 4, we will not dwell on them here. This carrier transport mechanism is illustrated in Fig. 9C. Absorption by a specialized carrier mechanism (from the rat intestine) has been shown to exist for several agents used in cancer chemotherapy (5-fluorouracil and 5-bromouracil) [37,38], which may be considered false nutrients in that their chemical structures are very similar to essential nutrients for which the intestine has a specialized transport mechanism. It would be instructive to examine some studies concerned with riboflavin and ascorbic acid absorption in humans, as these illustrate how one may treat urine data to explore the mechanism of absorption. If a compound is... 

The size and extent of many neurons presents a special set of challenges. Since protein synthesis for the entire neuron takes place in the cell body, which may represent only 0.1% of the total cell volume, growth and maintenance of neuronal processes requires timely, efficient delivery of material to axonal and dendritic domains. The idea that materials must be transferred from cell body to axon was suggested by Ramon y Cajal and other pioneers during the early part of this century. For many years, the existence of such transport processes could only be inferred. 

The norepinephrine transporter (NET) and the vesicular monoamine transporter (VMAT) are presynaptic components of the sympathetic neurons. NET is a Na+ /Cl -dependent transport protein and responsible for the neurotransmitter uptake from the synaptic cleft into the cytoplasm of the neurons. This transport process, called uptake-1, reduces the amount and, thus, the effect of NE released into the synaptic cleft. NE is stored in the cytoplasm of the neurons in specialized vesicles by the H+-dependent transport protein VMAT. Two isoforms VMAT1 and VMAT2, are known. VMAT is localized in the vesicle membranes, and the vesicular storage protects NE from metabolism by monoamine oxidase (MAO), which is localized on the surface membrane of the mitochondria. Vice versa, nerve depolarisation causes NE release from the vesicles into the synaptic cleft by Ca+-mediated exocytose (Fig. 12) [79,132-136],... 

---