Compartmental membrane transport

Substrate availability to the cell is affected by the supply of raw materials from the environment. The plasma membranes of cells incorporate special and often specific transport proteins (translocases) or pores that permit the entry of substrates into the cell interior. Furthermore pathways in eukaryotic cells are often compartmentalized within cytoplasmic organelles by intracellular membranes. Thus we find particular pathways associated with the mitochondria, the lysosomes, the peroxisomes, the endoplasmic reticulum for example. Substrate utilization is limited therefore by its localization at the site of need within the cell and a particular substrate will be effectively concentrated within a particular organelle. The existence of membrane transport mechanisms is crucial in substrate delivery to, and availability at, the site of use. 

Examples of such intra cellular membrane transport mechanisms include the transfer of pyruvate, the symport (exchange) mechanism of ADP and ATP and the malate-oxaloacetate shuttle, all of which operate across the mitochondrial membranes. Compartmentalization also allows the physical separation of metabolically opposed pathways. For example, in eukaryotes, the synthesis of fatty acids (anabolic) occurs in the cytosol whilst [3 oxidation (catabolic) occurs within the mitochondria. 

Investigations in other laboratories have also supported the hypothesis that carotenoid biosynthesis may be compartmentalized and transport associated. In prelimin investigations, lipid globules and cytoplasmic membranes were isolated by differential centrifugation (Peschek R, person communication, 1992). The purity of... 

Another property of cell membranes in addition to compartmentalization is their ability to fuse. This is important for intracellular vesicle transport between intracellular organelles as well as, for example, for the fusion of enveloped viruses with target cell membranes. 

Other processes that lead to nonlinear compartmental models are processes dealing with transport of materials across cell membranes that represent the transfers between compartments. The amounts of various metabolites in the extracellular and intracellular spaces separated by membranes may be sufficiently distinct kinetically to act like compartments. It should be mentioned here that Michaelis-Menten kinetics also apply to the transfer of many solutes across cell membranes. This transfer is called facilitated diffusion or in some cases active transport (cf. Chapter 2). In facilitated diffusion, the substrate combines with a membrane component called a carrier to form a carrier-substrate complex. The carrier-substrate complex undergoes a change in conformation that allows dissociation and release of the unchanged substrate on the opposite side of the membrane. In active transport processes not only is there a carrier to facilitate crossing of the membrane, but the carrier mechanism is somehow coupled to energy dissipation so as to move the transported material up its concentration gradient. 

The best known functions of the ER require a high membrane surface and/or a separate, specific microenvironment within the organelle. Although many enzymes hosted by the ER use its membranous structure only as a scaffold, others are compartmentalized within the ER i.e., their active site is localized in the lumen. The activity of these enzymes usually is dependent on the special composition of the luminal compartment. The enzymes often receive their substrates and cofactors from or release their products to the cytosol therefore, the transport of these compounds across the ER membrane is indispensable. This article focuses on this latter group of the ER enzymes, the functioning of which makes the ER a separate metabolic compartment of the eukaryotic cell. 

Compartmentation. The metabolic patterns of eukaryotic cells are markedly affected by the presence of compartments (Figure 30 3). The fates of certain molecules depend on whether they are in the cytosol or in mitochondria, and so their flow across the inner mitochondrial membrane is often regulated. For example, fatty acids are transported into mitochondria for degradation only when energy is required, whereas fatty acids in the cytosol are esterified or exported. 

The phosphoinositides are postulated to be localized in the plasma membrane (Mauco et aL, 1987) because of die agonist-induced hydrolysis of PIPj, but there are reason to believe that the phosphoinositides and their enzymes are compartmentalized (Vickers and Mustard, 1986 Nahaseta/., 1989 Kanoh era/., 1990 Suzuki era/., 1991 Grondin era/., 1991) and, as already mentioned, only 55 % of the phosphoinositides are metabolically active (Frnlich et aL, 1992) in human platelets. PIP and PIPj are in addition to be bound to PKC and plasmamembrane Ca -transport ATPase, also found to be associated with actin-binding proteins in the cytoskeleton (profilin and gelsolin), and probably involved... 

Membrane, with appropriate permeability characteristics, as well as, physicochemical properties, is used in bioartificial organs as selective barriers to compartmentalize isolated cells while allowing the transport of nutrients and metabolites to cells and the transport of catabohtes and specific metabolic products to blood. Moreover, the membrane avoids the contact between immune system components with xenogenic cells to prevent immunological response and rejection of xenograft. 

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