The Functions of Membranes

As already mentioned, three important functions take place in or on membranes (in addition to the structural role of membranes as the boundaries and containers of all cells and of the organelles within eukaryotic cells). The first of these functions is transport. Membranes are semipermeable barriers to the flow of substances into and out of cells and organelles. Transport through the membrane can involve the lipid bilayer as well as the membrane proteins. The other two 

How does transport through membranes take place  

Glucose passes into an erythrocyte via glucose permease by facilitated diffusion. Glucose flows using its concentration gradient via passive transport. (Adapted from Lehninger, Principles of Biochemistry, Third Edition, by David L. Nelson and Michael M. Cox. 1982, 1992, 2000 by Worth Publishers. Used with permission ofW. H. Freeman and Company.) 

The plots for facilitated diffusion are similar to plots of enzyme-catalyzed reactions (Chapter 6), and they display saturation behavior. The value v stands for velocity of transport. 5 is the concentration of the substrate being transported. 

Under normal circumstances, the concentration of K+ is higher inside a cell than in extracellular fluids (but the concentration ofNa is lower inside the cell than out The energy required 

---

There are other ways in which the lateral organization (and asymmetry) of lipids in biological membranes can be altered. Eor example, cholesterol can intercalate between the phospholipid fatty acid chains, its polar hydroxyl group associated with the polar head groups. In this manner, patches of cholesterol and phospholipids can form in an otherwise homogeneous sea of pure phospholipid. This lateral asymmetry can in turn affect the function of membrane proteins and enzymes. The lateral distribution of lipids in a membrane can also be affected by proteins in the membrane. Certain integral membrane proteins prefer associations with specific lipids. Proteins may select unsaturated lipid chains over saturated chains or may prefer a specific head group over others. 

Before the first indication of the existence of cannabinoid receptors, the prevailing theory on the mechanism of cannabinoid activity was that cannabinoids exert their effects by nonspecific interactions with cell membrane lipids (Makriyannis, 1990). Such interactions can increase the membrane fluidity, perturb the lipid bilayer and concomitantly alter the function of membrane-associated proteins (Loh, 1980). A plethora of experimental evidence suggests that cannabinoids interact with membrane lipids and modify the properties of membranes. However, the relevance of these phenomena to biological activities is still only, at best, correlative. An important conundrum associated with the membrane theories of cannabinoid activity is uncertainty over whether cannabinoids can achieve in vivo membrane concentrations comparable to the relatively high concentrations used in in vitro biophysical studies (Makriyannis, 1995). It may be possible that local high concentrations are attainable under certain physiological circumstances, and, if so, some of the cannabinoid activities may indeed be mediated through membrane perturbation. 

An important question arises about the effects of phospholipid composition and the function of membrane-bound enzymes. The phospholipid composition and cholesterol content in cell membranes of cultured cells can be modified, either by supplementing the medium with specific lipids or by incubation with different types of liposomes. Direct effects of phospholipid structure have been observed on the activity of the Ca2+-ATPase (due to changes in the phosphorylation and nucleotide binding domains) [37]. Evidence of a relationship between lipid structure and membrane functions also comes from studies with the insulin receptor [38]. Lipid alteration had no influence on insulin binding, but modified the kinetics of receptor autophosphorylation. 

Only ADP is phosphorylated to form ATP in glycolysis, oxidative phosphorylation, and photophosphorylation. ATP provides the energy, directly or indirectly, to drive most biosynthetic reactions. The functions of membranes such as active transport and osmotic relations, which regulate the volume of cells, are energy dependent. The structural organization, contraction, and orientation of chromosomes and microtubules of the spindle apparatus during mitosis depend on ATP energy. The intracellular concentrations and stoichiometric relations of ATP, ADP, and AMP also modulate cellular metabolism. 

Lipids (fats) are the other important components of cell membranes. Along with cholesterol, also a component of the cell membrane, they have acquired a bad name, but they arc nonetheless essential to the function of membranes as selective barriers to the movement of molecules. 

The functionalization of membrane surface could be achieved by the grafting of functional groups created by luminous gas. Such a treatment has been used to attach amino groups to polymer surfaces. The luminous gas of ammonia, a mixture of... 

B. diminuta/ca. Another advantage and necessity of membrane filters is the fact that these are integrity testable. Therefore, flaws or defects can be detected, which is critical, due to the function of membrane filters, mainly in separating microorganisms from pharmaceutical solutions. 

The mechanisms through which cholesterol can influence the functioning of membranes is summarized as follows ... 

To understand the function of membrane-active peptides, it is important to know the structure and orientation of the peptide in the membrane. As is evident from Figure 18.1, it is possible to distinguish between, for example, carpet and pore mechanisms of action by determining the peptide s orientation in the membrane. Various techniques, such as electron spin resonance (ESR) [35], infrared (IR) spectroscopy [36-38], circular dichroism (CD) [35, 39,40], and solid-state NMR (SSNMR) [4-7] are used to investigate membrane-active peptides in a quasi-native lipid bilayer environment. In the following sections, methods to determine peptide structure and orientation are presented. 

Central nervous system (CNS) depression caused by acute inhalation exposure to volatile aliphatic and aromatic petroleum hydrocarbons is generally thought to occur when the lipophilic parent hydrocarbon dissolves in nerve cell membranes and disrupts the function of membrane proteins by disrupting their lipid environment or by directly altering protein conformation. Oxidative metabolism of CNS-depressing hydrocarbons reduces their lipophilicity and represents a process that counteracts CNS-depression toxicity. More detailed information on this mechanism of toxicity can be found in ATSDR profiles on toluene (ATSDR 1994), ethylbenzene (ATSDR 1999a), and xylene (ATSDR 1995d). 

Chloramphenicol - L-T reo chloramphenicol, an isomer which does not inhibit mitochondrial protein synthesis, did exert an effect on bone marrow in rats.147 Previous studies had related the two effects. A resistance factor elaborated by Pseudomonas aeruginosa K-102 was thought to control the function of membrane permeability of the cells.11 8... 

Of course, there are many membranes into which anions may enter and cations are excluded. Some important examples will be discussed in the following presentation. It turns out that basic principles of the functioning of membranes in electro analysis can be illustrated very well using the example of the glass membrane which is involved in the pH electrode. This is discussed in detail in the following section. Then, the functioning of liquid membranes is considered in the next section. 

Figure 1. Retained solute as the function of membrane refection and volumetric condensation...

A question of some importance is whether cholesterol in biomembranes can affect the function of membrane proteins. Several systems have now been examined and a number of conflicting ideas have been put forward. Let us first consider what is known about intrinsic protein-cholesterol interactions. 

Lipids are not covalently bound in membranes but rather interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. The fluidity, supermolecular-phase propensity, lateral pressure and surface charge of the bilayer matrix is largely determined by the collective properties of the complex mixture of individual lipid species, some of which are shown in Fig. 8.1. Lipids also interact with and bind to proteins in stiochiometric amounts affecting protein structure and function. The broad range of lipid properties coupled with the dynamic organization of lipids in membranes multiplies their functional diversity in modulating the environment and therefore the function of membrane proteins. 

There is much more awareness of the possible effect of the electric fields normal to the plane of the membrane on the structure and on the function of membrane proteins. However, no such relation was experimentally documented. There is an appreciable amount of information on the potential dependence of channel conductance, which is assumed to be caused by shifts of charged groups within the channel (41). These shifts correspond to small changes in conformation that could not be detected by methods sensitive to the secondary structure of the proteins. In the present and in some previous reports (7, 8), we have shown that membrane potentials of comparable magnitude to the physiological membrane potentials are sufficient to modulate the secondary structure of membrane proteins. The effect may be direct or indirect. The indirect effect shifts part of the molecular fraction immersed... 

Azoles inhibit 14-a-sterol demethylase, a microsomal CYP that is essential for ergosterol biosynthesis (Figure 48-1). This results in the accumulation of 14-a-methylsterols that disrupt the packing of acyl chains of phospholipids and impair the functions of membrane-bound enzymes such as ATPase and those of the electron transport system, resulting in inhibited fungal growth. 

---