Portion of the lipid molecule

The hydrocarbon portion of the lipid molecule may be saturated [Fig. 3(A)] or unsaturated [Fig. 3(B),(Q]. The moelcules may be unsubstituted or substitution of an atom or chemical group, e.g., carboxylic acid or alcohol, for a hydrogen can occur anywhere along the hydrocarbon chain [Fig. 3(D)]. 

Fig. 52.—Sites of action of phospholipases A and D on lysophosphatidylcholine. The horizontal lines indicate the portion of the lipid molecule assumed to be complexed with amylose. (Reprinted with permission from T. Gaillard, Recent Adv. Phytochem., 17 (1983) 111— 136.)...

In contrast to MDA and hydroxynonenai, other aldehyde products of lipid peroxidation are hydrophobic and remain closely associated with LDL to accumulate to mil-limolar concentrations. Aldehydes at these elevated levels react with the protein portion of the LDL molecule, apolipoprotein B (apoB). Accumulated aldehydes bind the free amino groups from lysine residues in addition to other functional groups (-OH, -SH) on the apoB polypeptide. Consequently, the protein takes on a net negative charge and complete structural rearrangement results in the formation of ox-LDL. ox-LDL is no longer recognized by the LDL receptor, and has several pro-inflammatory properties (discussed below). 

To move through the membrane (change sides or transverse diffusion), a molecule must be able to pass through the hydrophobic portion of the lipid bilayer. For ions and proteins, this means that they must lose their interactions with water (desolvation). Because this is extremely difficult, ions and proteins do not move through membranes by themselves. Small molecules such as C02, NH3 (but not NH ). and water can diffuse through membranes however, most other small molecules pass through the lipid bilayer very slowly, if at all. This permeability barrier means that cells must develop mechanisms to move molecules from one side of the membrane to the other. 

Since valinomycin transports K+ specifically, it must bind the ion rather than provide a channel, as does gramicidin. Since transport can occur only when the membrane is fluid and since valinomycin is a small molecule, this suggests that the valinomycin-K+ complex must move through the membrane i.e., it behaves as a mobile carrier. The hydrocarbon side chains of the cyclic structure can be imagined on the outside of the structure, thus making the latter compatible with the hydrocarbon portion of the lipid bilayer. The inside contains the 12 carbonyl groups of the ester and amide bonds, six of which coordinate the K+ in the space at the center of the structure (Fig. 6-19). 

Some portions of the apolipoprotein molecules are nonpolar (hydro-phobic), and these are usually oriented toward the inside (near the lipid portion) of the complex. Polar amino acid side chains in the protein portions are oriented toward the outside of the complex, where they associate with the aqueous environment, rendering the complex soluble in blood plasma. This type of structure resembles that of micelles. 

Neuraminidase isolated from the culture filtrate of Arthrobacter ureafaciens has been characterized in detail with respect to its action on glycolipids. Strong electrolytes had a reversible inhibitory effect on the action of the enzyme on brain gangliosides in accordance with Debye-Hiickel effect of ionic environment on ionic activity, and resulted in an acidic shift and a broadening of the pH optimum. Both ionic and non-ionic detergents markedly enhanced the activity of the thiol-sensitive enzyme on the gangliosides, and caused an acidic shift of the pH optimum. It was suggested that the hydrophobic ceramide moiety increases affinity of the lipid substrate to the enzyme, but inhibits hydrolysis of the substrate, possibly due to its hydrophobic interaction with hydrophobic portions of the enzyme molecule. 

Lipids are amphipathic inolecules composed of a polar, hydrophilic head connected to a nonpolar, hydrophobic hydrocarbon tail. When in an aqueous environment, lipids tend to associate noncovalently. There are two driving forces for this association the hydrophobic effect due to the nonpolar tails, and the van der Waals interactions between the hydrocarbon portions of the molecules. This behavior in water can cause lipids to spontaneously form surface monolayers, bilayers, micelles, or vesicles, depending on the structures of the head and tail of the lipid molecule. We shall direct our attention here to the cell membrane bilayer, the most important of these biological assemblies. 

The amino groups of the DAB residues in the cyclic polypeptide portion of the polymyxin molecule are necessary for the antimicrobial activity, which is reduced on acetylation [142]. Removal of the side chain from the molecule also reduces the activity by about 70% [143]. Various techniques have been used to probe the molecular interaction between polymyxin and the membrane components. Few [144] showed that polymyxin interacts with monolayers prepared from lipids and phospholipids of bacterial origin. Penetration of the mono-layers was followed by an increase in surface pressure, and polymyxin E was... 

In particular, the planar bilayer phase manifests itself in several thermotropic subphases Lp, L p, and )" that differ as to the orientational order and mobility of the lipid molecules. The common characteristic of this polymorphism is that the molecules arrange themselves into structures with a hydrophobic core by orienting their hydrophilic portions towards the water environment. 

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