Transport carrier molecules

The primary functions of albumin are to help maintain the osmotic (oncotic) transmural pressure differential that ensures proper mass exchange between blood and interstitial fluid at the capillary level and to serve as a transport carrier molecule for several hormones and other small biochemical constituents (such as some metal ions). The primary function of the globulin class of proteins is to act as transport carrier molecules (mostly of the a and p class) for large biochemical substances, such as fats (lipoproteins) and certain carbohydrates (muco- and glycoproteins) and heavy metals (mineraloproteins), and to work together with leukocytes in the body s immune system. The latter function is primarily the responsibflity of the y class of immunoglobulins, which have antibody activity. The primary function of fibrinogen is to work with thrombocytes in the formation of a blood clot — a process also aided by one of the most abundant of the lesser proteins, prothrombin (MW 62,000). 

Cell membranes are lipophilic and designed to be barriers against large anionic molecules, although there is a natural mechanism for intercellular transport of anionic oligonucleotides. In order to enhance membrane transport, antisense oligonucleotides are frequentiy modified by covalent attachment of carrier molecules or lipophilic groups. 

Several authors " have suggested that in some systems voids, far from acting as diffusion barriers, may actually assist transport by permitting a dissociation-recombination mechanism. The presence of elements which could give rise to carrier molecules, e.g. carbon or hydrogen , and thus to the behaviour illustrated in Fig. 1.87, would particularly favour this mechanism. The oxidant side of the pore functions as a sink for vacancies diffusing from the oxide/gas interface by a reaction which yields gas of sufficiently high chemical potential to oxidise the metal side of the pore. The vacancies created by this reaction then travel to the metal/oxide interface where they are accommodated by plastic flow, or they may form additional voids by the mechanisms already discussed. The reaction sequence at the various interfaces (Fig. 1.87b) for the oxidation of iron (prior to the formation of Fe Oj) would be... 

Certain solutes, eg, glucose, enter cells by facilitated diffusion, along a downhill gradient from high to low concentration. Specific carrier molecules, or transporters, are involved in such processes. 

In the process of mediated transport, carrier proteins embedded within the plasma membrane assist in the transport of larger polar molecules into or out of the cell. When a given substance attaches to a specific binding site on the carrier protein, the protein undergoes a conformational change such that this site with the bound substance moves from one side of the plasma membrane to the other. The substance is then released. Mediated transport displays three important characteristics influencing its function ... 

Glucose and galactose enter the absorptive cells by way of secondary active transport. Cotransport carrier molecules associated with the disaccharidases in the brush border transport the monosaccharide and a Na+ ion from the lumen of the small intestine into the absorptive cell. This process is referred to as "secondary" because the cotransport carriers operate passively and do not require energy. However, they do require a concentration gradient for the transport of Na+ ions into the cell. This gradient is established by the active transport of Na+ ions out of the absorptive cell at the basolateral surface. Fructose enters the absorptive cells by way of facilitated diffusion. All monosaccharide molecules exit the absorptive cells by way of facilitated diffusion and enter the blood capillaries. 

At this point, the acyl-CoA is still in the cytosol of the muscle cell. Entry of the acyl-CoA into the mitochondrial matrix requires two translocase enzymes, carnitine acyl transferase I and carnitine acyl transferase II (CAT I and CAT II), and a carrier molecule called carnitine the carnitine shuttles between the two membranes. The process of transporting fatty acyl-CoA into mitochondria is shown in Figure 7.15. 

Hydrophilic or water-soluble drugs do not cross membranes. They stay in the bloodstream for durations that are normally short, lasting on the order of seconds, and mediate responses of short duration. In contrast, hydrophobic drugs require carrier molecules for transport through the bloodstream. Hydro-phobic drugs remain in the bloodstream and can persist for hours and days, providing much longer effects. 

When deficient in iron, bacteria and fungi produce and excrete to the extracellular medium low molecular weight, specific iron-carrier molecules, called siderophores. These siderophores bind ferric ions, to form soluble complexes. The complexed ferric ions are transported into the cell through high-affinity and energy-dependent receptor proteins located on the outer membrane. In Gram-negative bacteria, such as E. coli, the most studied system, siderophore-iron complexes are transported initially to the periplasm. 

Inhibition of whole chain electron transport can result from (a) Interaction of the inhibitor with a redox component of the pathway or (b) interaction with carrier systems that transport substrate molecules across the inner membrane. The latter interaction could be direct or indirect. Because electron transport associated with the oxidation of malate, succinate, and exogenous NADH were all inhibited, but to differing extents, a specific Interaction with a single redox component of the inner mitochondrial membrane does not seem to be involved. 

For the alkali metal cations, the stability (14) and permeability (43) sequences for dicyclohexyl-18-crown-6 have been found to be the same (K+ > Rb+ > Cs+ > Na+ > Li+). Thus, a direct relationship exists between the ability of a macrocyclic compound to complex a particular cation (as measured by the log K value for complex formation) and its influence on the biological transport of that cation. Furthermore, it would appear that the biological ion-transport mechanism may in part be due to the complexation properties of the macrocyclic carrier molecules. This subject with respect to cyclic antibiotics has been treated extensively by Si wow and co-workers (2). 

Leukocyte Adhesion Deficiency Type 2. Patients with this condition have a defect in the transport or production of the carrier molecule for the carbohydrate L-fucose (guanosine disphosphate L-fucose). The lack of fucose affects the ability of neutrophils to interact with ligands on endothelial cells such as P-selectins and E-selectins (81). Patients are susceptible to recurrent infections similar to those afflicting patients with type 1 leukocyte adhesion deficiency, have periodontal problems, and, in addition, may exhibit growth retardation and neurologic defects. Treatment with oral fucose has been known to be effective in reducing the frequency of infections (80). 

Bacitracin inhibits the dephosphorylation of this lipid carrier, a step essential to the carrier molecule s ability to accept cell wall constituents for transport. 

A silane-based CVD reactor suitable for performing high-temperatnre anneals in an Si- rich ambient was used for these experiments [86]. The samples were placed on a SiC-coated graphite susceptor and an RF induction coil used to heat the susceptor to temperatures on the order of 1,600-1,800°C. Silane and argon were the two process gases used, where Ar not only serves as a dilutant gas but also as a carrier gas to transport silane molecules to the crystal surface. All the implant annealing experiments were performed at atmospheric pressure. 

In general, the specific constituents of milk are synthesized from small molecules absorbed from the blood. These precursors are absorbed across the basal membrane but very little is known about the mechanism by which they are transported across the membrane. Since the membrane is rich in lipids, and precursors are mostly polar with poor solubility in lipid, it is unlikely that the precursors enter the cell by simple diffusion. It is likely, in common with other tissues, that there are specialized carrier systems to transport small molecules across the membrane such carriers are probably proteins. 

There are, however, various types of active transport systems, involving protein carriers and known as uniports, symports, and antiports as indicated in Figure 3.7. Thus, symports and antiports involve the transport of two different molecules in either the same or a different direction. Uniports are carrier proteins, which actively or passively (see section "Facilitated Diffusion") transport one molecule through the membrane. Active transport requires a source of energy, usually ATP, which is hydrolyzed by the carrier protein, or the cotransport of ions such as Na+ or H+ down their electrochemical gradients. The transport proteins usually seem to traverse the lipid bilayer and appear to function like membrane-bound enzymes. Thus, the protein carrier has a specific binding site for the solute or solutes to be transferred. For example, with the Na+/K+ ATPase antiport, the solute (Na+) binds to the carrier on one side of... 

Thus, a specific carrier molecule is involved, but the process relies on a concentration gradient, as does passive diffusion. The transport of glucose out of intestinal cells into the bloodstream occurs via facilitated diffusion and uses a uniport. 

Transporters Carrier proteins which transport molecules across a cell membrane. 

FIGURE 2—10. A transport carrier is used to shuttle molecules into cells that otherwise would not be able to get into the cell through the membrane. 

In order to accomplish selective shuttling of certain molecules across an otherwise impermeable membrane, other molecules known as transport carriers work to bind that molecule needing a trip inside the cell (Figs. 2—11 and 2—20 through 2—22). The transport carrier is thus itself a type of receptor. In order for some transport carriers to concentrate the shuttling molecules within the cell, they require energy. 

One example of molecular transport requiring energy is the reuptake of neurotransmitter into its presynaptic neuron, as already mentioned above. In this case, the energy comes from linkage to an enzyme known as sodium-potassium ATPase (Fig. 2—9). An active transport pump is the term for this type of organization of two neurotransmitters, namely a transport carrier and an energy-providing system, which function as a team to accomplish transport of a molecule into the cell (Fig. 2—11). 

FIGURE 2—20. The transport carrier for neurotransmitter reuptake is like a box car with reserved seats for molecules for neurotransmitter. Here the transport carrier is empty. Its tires are flat, and it is unable to transport neurotransmitter. 

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