Fatty acyl chains

Phase transitions have been characterized in a number of different pure and mixed lipid systems. Table 9.1 shows a comparison of the transition temperatures observed for several different phosphatidylcholines with different fatty acyl chain compositions. General characteristics of bilayer phase transitions include the following ... 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

The addition of double bonds to fatty acids in eukaryotes does not occur until the fatty acyl chain has reached its full length (usually 16 to 18 carbons). Dehydrogenation of stearoyl-CoA occurs in the middle of the chain despite the absence of any useful functional group on the chain to facilitate activation ... 

Fatty acid oxidation in mitochondria leads to the generation of large quantities of ATP by a process called P Oxidation that cleaves acetyl-CoA units sequentially from fatty acyl chains. The acetyl-CoA is oxidized in the citric acid cycle, generating further ATP. 

It has been proposed that the a-tocopheroxyl radical can be recycled back to tocopherol by ascorbate producing the ascorbyl radical (Packer etal., 1979 Scarpa et al., 1984). The location of a-tocopherol, with its phytyl tail in the membrane parallel to the fatty acyl chains of the phospholipids and its phenolic hydroxyl group at the memisrane-water interface near the polar headgroups of the phospholipid bilayer, enables ascorbate to donate hydrogen atoms to the tocopheroxyl radical. The suitability for ascorbate and tocopherol as chain-breaking antioxidants is exemplified (Buettner,... 

Effect of Cholesterol. Cholesterol inclusion into the lipid bilayers composed of DPPC or DSPC, eliminates apparent Tc and reduces permeability at and above the usual Tc. On the other hand, cholesterol inclusion increases packing of fluid bilayer composed of lipids with unsaturated fatty acyl chains. Since cholesterol rich liposomes are stable in plasma, cholesterol is commonly used as a liposomal component. 

The fate of injected liposomes is drastically altered by administration route, dose and size, lipid composition, surface modification, and encapsulated drugs. Liposomes encapsulating drugs are often administered iv, therefore, the stability of liposomes in plasma is important. When liposomes composed of PC with unsaturated fatty acyl chains are incubated in the presence of serum, an efflux of internal solute from the liposomes is observed. This increase in permeability is caused by the transfer of phospholipids to high density lipoprotein (HDL) in serum (55). To reduce the efflux of liposomal contents, cholesterol is added as a liposomal component... 

Figure 35 13C CPMAS NMR spectra of [l- 3C]Val- and [3- 3C]Ala-labelled bR reconstituted in DMPC bilayer (1 50 mole ratio) at various temperatures from 40 (A) to —10 °C (D). The methylene peak-position of the fatty acyl chain of the lipid at 32 and 30 ppm is a good indicator of the gel and liquid-crystalline phase, respectively. From Ref. 206 with...

FIGURE 2-7 Putative model of apoE in rHDL. Two molecules of apoE of a total of about four molecules per discoidal particle are depicted to circumscribe the periphery of a bilayer of phospholipids. The helical axes are orientated perpendicular to the phospholipid fatty acyl chains. Adapted from [36] with permission. 

Excitable membranes maintain and rapidly modulate substantial transmembrane ion gradients in response to stimuli 576 Specific lipid messengers are cleaved from reservoir phospholipids by phospholipases upon activation by various stimuli 576 Phospholipids in synaptic membranes are an important target in seizures, head injury, neurodegenerative diseases and cerebral ischemia 576 Some molecular species of phospholipids in excitable membranes are reservoirs of bioactive lipids that act as messengers 576 Mammalian phospholipids generally contain polyunsaturated fatty acyl chains almost exclusively esterified to the second carbon of glycerol 577... 

Phospholipase A2 catalyzes cleavage of the fatty acyl chain from the second carbon of the glycerol backbone of phospholipids 577 Calcium-ion-dependent phospholipase A2 with a preference... 

Seelig J. and Seelig A. (1974). Dynamic structure of fatty acyl chains in a phospholipid bilayer measured by DMR, Biochemistry, 13, 4839-4845. 

Fig. 2.—Chemical structure of lipid A of the Escherichia coli Re mutant strain F515. The hydroxyl group at position 6 constitutes the attachment site of Kdo. The numbers in circles indicate the number of carbon atoms present in the fatty acyl chains. The 14 0(3-OH) residues possess the (Reconfiguration. The glycosylic phosphate group may be substituted by a phosphate group (see Table I) (46,65,69).

The properties of membranes commonly studied by fluorescence techniques include motional, structural, and organizational aspects. Motional aspects include the rate of motion of fatty acyl chains, the head-group region of the phospholipids, and other lipid components and membrane proteins. The structural aspects of membranes would cover the orientational aspects of the lipid components. Organizational aspects include the distribution of lipids both laterally, in the plane of the membrane (e.g., phase separations), and across the membrane bilayer (phospholipid asymmetry) and distances from the surface or depth in the bilayer. Finally, there are properties of membranes pertaining to the surface such as the surface charge and dielectric properties. Fluorescence techniques have been widely used in the studies of membranes mainly since the time scale of the fluorescence lifetime coincides with the time scale of interest for lipid motion and since there are a wide number of fluorescence probes available which can be used to yield very specific information on membrane properties. 

The fluorescence lifetime is sensitive to the environment of the fluorophore, and in membranes this usually means the surrounding fatty acyl chains or the membrane protein interfacial region (see summary in Table 5.3). Generally, the lifetime of membrane-bound fluorophores is rather less sensitive to the types of subtle alterations which are encountered in membranes as compared to the fluorescence anisotropy parameters. The gel-to-liquid crystalline phase transition is a notable exception where most fluorophores show an alteration in lifetime properties. Although, again, the anisotropy (see below) is the most sensitive parameter in this regard, the fluorescence lifetime has been used with considerable success in the study of phase transitions and lateral phase separations. Fluorophores used to yield information on the... 

Another factor affecting the lifetime of a membrane fluorophore probe is its proximity to the surface. The lifetimes of the DPH, DPH-phosphatidyl-choline (DPH-PC), and trimethylammonium-DPH (TMA-DPH) probes decrease in the order DPH > DPH-PC > TMA-DPH, as the probe locates nearer to the surface of the lipid bilayer.(7) The same is found for the anthroyl-stearate probes.(8) More recently, it has been shown that with TMA-DPH, the lifetime appears to be fairly sensitive to the differences in lipid bilayer packing induced by differing degrees of unsaturation in the phospholipid fatty acyl chains.(9) This aspect of the use of TMA-DPH and possibly other probes remains to be further exploited. 

The motional characteristics of interest are typically those governed by the phospholipid fatty acyl chains and head-group region and the neutral lipid or protein components of membranes. Rotational motion can be subdivided into a structural component, the order or degree of orientational constraint,... 

Table 5.3. Alteration of Membrane Lipid Properties and the Resultant Approximate Directions of Changes of Fluorescence Parameters of a Typical Membrane Fluorophore Probe of the Fatty Acyl Chain Region0...

The fluorophore should be stable under the conditions of measurement. Some fluorophores (e.g., parinaric acid), for example, may be incorporated into phospholipids in natural membranes.(67) Conversely, phospholipids with the fluorophore attached to one of the fatty acyl chains (e.g., DPH-PC) may be cleaved by the action of phospholipases. Also, DPH is susceptible to photobleaching so that a low excitation intensity has to be used. Parinaric acids are liable to oxidize and therefore have to be kept under argon. 

Figure 7. Relationship of oxidation and degree of polyunsaturation. Polyunsaturation is measured as the methylene bridge index (MBI), which is a more precise measure of extent of unsaturation and oxidizability than the double bond index. It is the mean number of 6is-allylic methylene bridge positions per fatty acid (or fatty acyl chain) in a lipid ensemble. The rate of lipid radical formation measures formation of an oxidative product, while O2 consumption (% O2 lost per sec) is a measure of utilization of a reactant. (Drawn using our data abstracted from Wagner, B.A., Buettner, G.R., and Bums, C.P. 1994, Biochemistry 33 4449-4453).

During the reaction, acetate, or the growing fatty acyl chain is initially esteri-fied to the sulfhydryl group of a cysteine residue of the enzyme. 

Tail group-Fatty acyl chains Rj and R 2 (Cl 4—18 in length) ... 

The physical properties of the fatty acids, and of compounds that contain them, are largely determined by the length and degree of unsaturation of the hydrocarbon chain. The nonpolar hydrocarbon chain accounts for the poor solubility of fatty acids in water. Laurie acid (12 0, Mx 200), for example, has a solubility in water of 0.063 mg/g—much less than that of glucose (Mt 180), which is 1,100 mg/g. The longer the fatty acyl chain and the fewer the double bonds, the lower is the solubility... 

FIGURE 11-3 Fluid mosaic model for membrane structure. The fatty acyl chains in the interior of the membrane form a fluid, hydrophobic region. Integral proteins float in this sea of lipid, held by hydrophobic interactions with their nonpolar amino acid side chains. Both proteins and lipids are free to move laterally in the plane of the... 

Membranes are composed of lipids and proteins in varying combinations particular to each species, cell type, and organelle. The fluid mosaic model describes features common to all biological membranes. The lipid bilayer is the basic structural unit. Fatty acyl chains of phospholipids and the steroid nucleus of sterols are oriented toward the interior of the bilayer their hydrophobic interactions stabilize the bilayer but give it flexibility. 

Length of a Fatty Acid Molecule The carbon carbon bond distance for single-bonded carbons such as those in a saturated fatty acyl chain is about 1.5 A. Estimate the length of a single molecule of palmitate in its fully extended form. If two molecules of palmitate were placed end to end, how would their total length compare with the thickness of the lipid bilayer in a biological membrane ... 

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