Biomembrane active transport

The volume of distribution of a peptide or protein drug is determined largely by its physico-chemical properties (e. g., charge, lipophilicity), protein binding, and dependency on active transport processes. Due to their large size - and therefore limited mobility through biomembranes - most therapeutic proteins have small volumes of distribution, typically limited to the volumes of the extracellular space [26, 51]. 

Genes of protoberberine biosynthesis are abundantly expressed in rhizomes of Thalictrum flavum, but were also active in roots and other organs (Samanani et al. 2005). In roots, transcripts were localized in the immature endodermis and root pericycle. In rhizomes transcripts were found in the protoderm of leaf primordial. As known from other plants, these data show that the sites of synthesis are not identical with the sites of accumulation. In many instances, a long-distance transport must occur. If this is the case, alkaloids have to pass several biomembranes. ABC-transporters and H+-alkaloid antiporters can be involved (see Chapter 1). 

Transport of molecules across biomembranes can be classified mechanistically into the following types 1) active transport via carriers, 2) passive transport, which comprises a) simple diffusion and b) facditated diffusion, and 3) endocytosis/transcytosis. 

Membran systems are known to play an important role in functioning biological objects (in mass transfer processes, passive and active transport of substance, regulation of an endocellular metabolism, in bio-energetics, etc.). Unique properties of biomembranes are caused by their structure, in particular, presence of bimolecular focused layers of lipids. At the same time, one of the main disadvantages of modelling lipid membran systems (monolayers, flat bilayers, liposomes), is their low stability in time and to action of external factors. 

The permeation of most drugs through cellular membranes is by the process of passive diffusion, a nonsaturable process that follows first-order kinetics. Concentration gradient and lipid solubility of the drug are important determinants of the rate of diffusion. Only a few drug molecules are substrates for active transport processes (eg, tubular secretion of beta-lactam antibiotics) these are saturable at high concentrations. Only very small ions (eg, Li+) or drugs (eg, ethanol) may penetrate biomembranes via aqueous pores. 

Active transport a process in which solute molecules or ions move across a biomembrane against a concentration gradient. Since thermodynamic work... 

Facilitated diffusion passive transport, the movement of specific compounds across a biomembrane from higher to lower concentration, but at a rate greater than simple diffusion. F. d. is saturable, meaning that above a certain concentration, the rate is not dependent on the substrate concentration. Furthermore, it is stereospecific and susceptible to competitive inhibition. Together, these properties indicate that the process is mediated by a carrier or pore protein in the membrane. F.d. differs from Active transport (see) in not requiring energy. A class of substances called lonophores (see) mimic the carriers of F.d. by making membranes permeable to certain ions. Antibiotics that act in this way are called transport antibiotics. 

With the above-mentioned background, it is informative to describe an application of the N- P equation as applied to the nerve axon, which is surrounded by a plasma membrane. One of the main functions of the plasma membrane is to control the passage of ions and molecules into and out of the cell. For most biomembranes, the intracellular [K+]i greatly exceeds extracellular [K+]o, and the opposite is true for the extracellular [Na+]o and [Cl ]o. These concentration differences are due to the active transport system embedded in the lipid bilayer of the plasma membrane [3]. 

Owing to complex structural and environmental factors associated with biomembranes, numerous investigators used different techniques and carried out studies on model systems in order to understand the fundamental life processes. These include ion accumulation or active transport, conduction of nerve impulses, energy transduction, protein synthesis, permeability barrier of ions and molecules, immunological reactions, phagocytosis and pinocytosis, and so on, in physical and chemical terms [3]. Under separate headings below, different model systems will be described. 

The transport of specific ions is a common function of a biomembrane. It is observed in an active transport of ions through the cell wall, a proton transport in oxidative phosphorylation, a selective transport of K and Na through the protoplasmic membrane, etc. To develop synthetic membrane having such functions is an important objective of polymer chemistry. 

In general, the functions linked to biomembranes (electron transfer, energy coupling, active transport, hormone action etc.) are known in better detail than the structures to which they are associated. 

Active Ion Transport as a Consequence of Stationary State Situations at Asymmetric Biomembranes... 

Although the author of this review is far from being an expert in the field of biomembrane research, some literature studied so far seems to indicate that the molecular mechanisms of the active ion transport are still not known 107). 

Except the special case of large particles and proteins that enter the cell by endocy-tosis [19], the transport of molecules across biomembranes can be divided into two categories [20] active and passive transport. 

It has been recognised for some time (see for example reference 1), that surfactants can increase the rate and extent of transport of solute molecules through biological membranes by fluidisation of the membrane. It is only recently, however, that sufficient work has been carried out to allow some analysis of structure-action relationships. In this overview an attempt is made, by reference to our own work and to work in the literature, to define those structural features in polyoxyethylene alkyl and aryl ethers which give rise to biological activity, especially as it is manifested in interactions with biomembranes and subsequent increase in the transport of drug molecules. 

Photosynthesis can be affected in many ways. Metals can influence biosynthesis of biomembranes and photosynthetic pigments, especially chlorophyll. They may inactivate enzymes by oxidising SH-groups necessary for catalytic activity or by substitution for other divalent cations in metalloenzymes. They finally can also interact with the photosynthetic electron transport and with the related photophosphorylation. 

There are several mechanisms for explaining how biological membranes can transport charged or uncharged substrates against their thermodynamic forces. It is widely accepted that cross-transports by a protein are discrete events. Biomembranes contain enzymes, pores, charges or membrane potentials, and catalytic activities associated with the transport of substrates. It is well established that the electrostatic interactions between the membrane and a charged... 

Disrupted calcium homoeostasis Normal concentrations of ionized calcium in the cytosol (0.05-0.2 pM), in the overall liver cell (0.5-2.0 pM) and in the extracellular space (1.0 pM) maintain the function of numerous Ca-dependent enzymes and structural elements of the liver cell. Calcium homoeostasis is maintained by the regulatory functioning of all Ca transportation systems, energy supply in the form of ATP and intactness of the biomembranes. Defective calcium homoeostasis can cause an increase in calcium in the cytosol, which in turn activates calcium-dependent enzymes, alters the metabolic functions of the cell and disrupts the gap junctions and tight junctions. These biochemical changes result in various forms of hepatocellular degeneration and ultimately in cell death, (s. fig. 21.12)... 

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