Biological membrane complexity

Most of the attention regarding amino acid complexation has been centred on animal fluids. There is considerable evidence, for example, that amino add complexes are involved in the (active) transport of metal ions across various biological membranes. Complexation of the trace elements is also considered essential in reducing concentrations of the free or hydrated metal ions and hence preventing the formation of unwanted hydroxy species and limiting the toxicity of the metal ions. 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

Just how fast can proteins move in a biological membrane Many membrane proteins can move laterally across a membrane at a rate of a few microns per minute. On the other hand, some integral membrane proteins are much more restricted in their lateral movement, with diffusion rates of about 10 nm/sec or even slower. These latter proteins are often found to be anchored to the cytoskeleton (Chapter 17), a complex latticelike structure that maintains the cell s shape and assists in the controlled movement of various substances through the ceil. 

FIGURE 22.20 The molecular architecture of PSI. PsaA and PsaB constitute the reaction center dimer, an integral membrane complex P700 is located at the lumenal side of this dimer. PsaC, which bears Fe-S centers and Fb, and PsaD, the interaction site for ferre-doxin, are on the stromal side of the thylakoid membrane. PsaF, which provides the plasto-cyaiiin interaction site, is on the lumenal side. (Adapted from Golbeck, J. H., 1992. Amiual Review of Plant Physiology and. Plant Molecular Biology 43 293-324.)... 

In terms of evolutionary biology, the complex mitotic process of higher animals and plants has evolved through a progression of steps from simple prokaryotic fission sequences. In prokaryotic cells, the two copies of replicated chromosomes become attached to specialized regions of the cell membrane and are separated by the slow intrusion of the membrane between them. In many primitive eukaryotes, the nuclear membrane participates in a similar process and remains intact the spindle microtubules are extranuclear but may indent the nuclear membrane to form parallel channels. In yeasts and diatoms, the nuclear membrane also remains intact, an intranuclear polar spindle forms and attaches at each pole to the nuclear envelope, and a single kinetochore microtubule moves each chromosome to a pole. In the cells of higher animals and plants, the mitotic spindle starts to form outside of the nucleus, the nuclear envelope breaks down, and the spindle microtubules are captured by chromosomes (Kubai, 1975 Heath, 1980 Alberts et al., 1989). 

Various types of research are carried out on ITIESs nowadays. These studies are modeled on electrochemical techniques, theories, and systems. Studies of ion transfer across ITIESs are especially interesting and important because these are the only studies on ITIESs. Many complex ion transfers assisted by some chemical reactions have been studied, to say nothing of single ion transfers. In the world of nature, many types of ion transfer play important roles such as selective ion transfer through biological membranes. Therefore, there are quite a few studies that get ideas from those systems, while many interests from analytical applications motivate those too. Since the ion transfer at an ITIES is closely related with the fields of solvent extraction and ion-selective electrodes, these studies mainly deal with facilitated ion transfer by various kinds of ionophores. Since crown ethers as ionophores show interesting selectivity, a lot of derivatives are synthesized and their selectivities are evaluated in solvent extraction, ion-selective systems, etc. Of course electrochemical studies on ITIESs are also suitable for the systems of ion transfer facilitated by crown ethers and have thrown new light on the mechanisms of selectivity exhibited by crown ethers. 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

Intact biological membranes are far more complex systems than even the lipid extracts (see Fig. 6). In hardly any case do the lipid components exceed 50% of the dry weight, as membranes intrinsically contain numerous proteins and various glycoconjugates. This diversity is most pronounced in the plasma membrane (irrespective of the genera) which is effectively amalgamated with the non-lipidic... 

Mercury (Hg) can occur in a large number of physical and chemical forms with a variety of properties, thus determining complex distribution, bioavailability, and toxicity patterns [1]. The most important chemical forms are elemental Hg (Hg°), ionic Hg (Hg2+ and Hg22+), and alkylmercury compounds. Because of their capability to permeate through biological membranes and to bioaccumulate and to biomagnificate through the trophic chain, alkylmercury compounds are the most toxic mercury species found in the aquatic environment [2]. 

Macrocyclic compounds with ion-chelating properties occur naturally and often function as ionophores, translocating ions across biological membranes many of these compounds are small cyclic polypeptides. Some natural carboxylic polyethers are selective for Li+ and are, therefore, ionophores for Li+. Monensin, shown in Figure Id, is a natural ionophore for Na+ but it will also complex with Li+ and it has been shown to mediate the transport of Li+ across phospholipid bilayers [21]. It has been proposed that synthetic Li+-specific ionophores have a potential role as adjuvants in lithium therapy, the aim being to reduce the amount of... 

The several theoretical and/or simulation methods developed for modelling the solvation phenomena can be applied to the treatment of solvent effects on chemical reactivity. A variety of systems - ranging from small molecules to very large ones, such as biomolecules [236-238], biological membranes [239] and polymers [240] -and problems - mechanism of organic reactions [25, 79, 223, 241-247], chemical reactions in supercritical fluids [216, 248-250], ultrafast spectroscopy [251-255], electrochemical processes [256, 257], proton transfer [74, 75, 231], electron transfer [76, 77, 104, 258-261], charge transfer reactions and complexes [262-264], molecular and ionic spectra and excited states [24, 265-268], solvent-induced polarizability [221, 269], reaction dynamics [28, 78, 270-276], isomerization [110, 277-279], tautomeric equilibrium [280-282], conformational changes [283], dissociation reactions [199, 200, 227], stability [284] - have been treated by these techniques. Some of these... 

The fluid mosaic model conveniently describes how the constituent molecules are ordered, and it correctly describes, in first order, some of the membrane s properties. However, it does not give explicit insight into why the biological membrane has a particular structure, and how this depends on the properties of the constituent molecules and the physicochemical conditions surrounding it. For this reason, only qualitative and no quantitative use can be made of this model as it pertains to permeation properties, for example. It is instructive to review the physicochemical principles that are responsible for typical membrane characteristics. In such a survey, it is necessary to discuss simplified cases of self-assembly first, before the complexity of the biological system may be understood. The focus of this quest for principles will therefore be more on the level of the molecular nature of the membrane, rather than viewing a... 

It is necessary to elaborate on yet another essential aspect of biological membranes, i.e. their complexity . This keyword points to the large number of different molecules that are usually found in the biological membrane. First of all, there is a large variety of lipid molecules. The lipid composition of the biological membranes varies from one species to another, and is adapted to meet the needs of organs, cells, organelles, etc. The variations in the head-tail... 

Ion pairs are outer-sphere association complexes, which have to be clearly distinguished from the organometallic complexes discussed in Section 6. Ion pair formation appears to be much less important in biological membranes as compared with octanol, because the charge of the ions at the membrane interphase can be balanced by counter charge in the electrolyte in the adjacent aqueous phase. The reactions involved in ion pair formation are depicted in Figures 5b for acids and 5c for bases, and the equilibrium constant K ix is defined as follows ... 

Copper complexes with organic acids from landfill leachates were contributing to the toxicity towards zebra fish embryos only if the molar mass of the complexes was sufficiently small to allow penetration of biological membranes [228]. Fractions of landfill leachate with M > 5000 g mol-1 had a... 

Indirect evidence of hydrophobic complex formation in biological membranes is also given by the modulation of the toxicity of catechol and chlor-ocatechol by Cu2+ [78], Whereas toxicity of higher chlorocatechols was decreased by the addition of Cu2+, it was increased in the case of catechol and monochlorocatechol. Tentative models to explain these findings include complex formation between mono-and di-deprotonated catechols and Cu2+, both in the aqueous and in the membrane phase. 

As seen above (equation (5)), the basis of the simple bioaccumulation models is that the metal forms a complex with a carrier or channel protein at the surface of the biological membrane prior to internalisation. In the case of trace metals, it is extremely difficult to determine thermodynamic stability or kinetic rate constants for the adsorption, since for living cells it is nearly impossible to experimentally isolate adsorption to the membrane internalisation sites (equation (3)) from the other processes occurring simultaneously (e.g. mass transport complexation adsorption to other nonspecific sites, Seen, (equation (31)) internalisation). 

For undersaturated ([M] < Km) systems with relatively fast internalisation kinetics (kmt > k, ), the uptake of trace metals may be limited by their adsorption. Because the transfer of metal across the biological membrane is often quite slow, adsorption limitation would be predicted to occur for strong surface ligands (small values of k ) with a corresponding value of Km (cf. equations (35) and (36)) that imposes an upper limit on the ambient concentration of the metal that can be present in order to avoid saturation of the surface ligands. More importantly, as pointed out by Hudson and Morel [7], this condition also imposes a lower limit on the carrier concentration. Since the complexation rate is proportional to the metal concentration and the total number of carriers, for very low ambient metal concentrations, a large number of carriers are required if cellular requirements are to be satisfied. 

Bioaccumulation is a complicated process that couples numerous complex and interacting factors. In order to directly relate the chemical speciation of an element to its bioavailability in natural waters, it will be necessary to first improve our mechanistic understanding of the uptake process from mass transport reactions in solution to element transfer across the biological membrane. In addition, the role(s) of complex lability and mobility, the presence of competing metal concentrations and the role(s) of natural organic ligands will need to be examined quantitatively and mechanistically. The preceding chapter... 

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