Acyl fatty acid chains hydrophobic interactions

Saturated and unsaturated free fatty acids may have antifungal potential, which effectiveness increases with their chain length (Kamem et al., 2009). An important role on microbial cells activity is played by hydrophobic groups of saturated fatty acids. The hydrophobicity increases with increasing the chain length, thus the solubility of fatty acids in aqueous environments decreases which prevents some interactions between these hydrophobic groups and the acyl chains of the membranes phospholipids. 

N-Myristoylation is achieved by the covalent attachment of the 14-carbon saturated myristic acid (C14 0) to the N-terminal glycine residue of various proteins with formation of an irreversible amide bond (Table l). 10 This process is cotranslational and is catalyzed by a monomeric enzyme called jV-myri s toy 11ransferase. 24 Several proteins of diverse families, including tyrosine kinases of the Src family, the alanine-rich C kinase substrate (MARKS), the HIV Nef phosphoprotein, and the a-subunit of heterotrimeric G protein, carry a myr-istoylated N-terminal glycine residue which in some cases is in close proximity to a site that can be S-acylated with a fatty acid. Functional studies of these proteins have shown an important structural role for the myristoyl chain not only in terms of enhanced membrane affinity of the proteins, but also of stabilization of their three-dimensional structure in the cytosolic form. Once exposed, the myristoyl chain promotes membrane association of the protein. 5 The myristoyl moiety however, is not sufficiently hydrophobic to anchor the protein to the membrane permanently, 25,26 and in vivo this interaction is further modulated by a variety of switches that operate through covalent or noncovalent modifications of the protein. 4,5,27 In MARKS, for example, multiple phosphorylation of a positively charged domain moves the protein back to the cytosolic compartment due to the mutated electrostatic properties of the protein, a so-called myristoyl-electrostatic switch. 28 ... 

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... 

Lipid moieties can impart good stability to polymeric micelles since the presence of two fatty acid acyls increases the hydrophobic interactions between polymeric chains in the micelle core. Indeed, no dissociation into individual polymeric chain was observed upon the chromatography of serial dilutions of diacyllipid-PEO conjugates (Trubetskoy and Torchilin, 1995). 

An explanation for the fact that the fatty acids synthesized by the soluble animal and yeast systems are of relatively uniform chain length has been given by Lynen et al. [250]. It is reasoned that the probabihty of chain termination is enhanced—that is, deacylation or transfer to CoA—as the residence time of the saturated acyl group on pantetheine prosthetic group is increased. The interaction of the elongated, hence more hydrophobic, acyl group with a site on the enzyme would tend to increase the residence time and thereby favor chain termination rather than condensation and further elongation. 

The crystalline lattice is stabilized by hydrophobic interaction along the acyl residues. Correspondingly, the energy and therefore the temperature required to melt the crystal increase with an increased number of carbons in the chain. Odd-numbered as well as unsaturated fatty acids can not be uniformly packed into a crystalline lattice as can the saturated and even-numbered acids. The odd-numbered acids are slightly interfered by their terminal methyl groups. 

Figure 3.7 Model of intermolecular fatty acid synthetase mechanism in the a2 2 protomer of yeast. A, acetyl transferase E, enoyl reductase D, dehydratase P, palmitoyl transferase M, malonyl transferase C, 5-ketoacyl synthase R. )5-ketoacyl reductase ACP, acyl carrier protein. Dotted lines and arrows delineate the route taken by intermediates when sequentially processed on different FAS domains. Numbers indicate the reaction sequence. Catalytically active dohnains, at a specific moment, are marked by bold lines. Shaded areas on E and P domains potentially interact by hydrophobic attraction in the presence of palmitate (b). On the protomer depicted in (a) fatty acyl chain elongation occurs in one half of the a2 2 protomer. In (b) chain termination is induced by hydrophobic interaction between E> bound palmitate and P. Subsequently, palmitate Is transferred to Its O-ester binding site on P. Inactivation of the left half of simultaneously activates its right half (b). Redrawn from Schweizer (1984) with permission of the author and Elsevier Science Publishers, BV. From Fatty Acid Metabolism and its Regulation (1984) (ed. S. Numa), p. 73, Figure 7.

Intrinsic proteins may be anchored in the membrane by several different mechanisms. Of these, the hydrophobic interaction of an amino acid sequence with the interior of the lipid bilayer is the most common. Such interactions include hydrophobic sequences at one end of the protein only as well as polypeptide chains which traverse the membrane (several times). In addition, some proteins may be attached through interactions with lipid. Thus, fatty acid acylation of the NH2-terminus or the formation of fatty acid thioesters with cysteine residues have been observed. In addition, a number of membrane proteins are believed to be covalently attached to phosphatidylinositol. 

Integral proteins are dissolved into the lipid bilayer of the membrane through interactions of the hydrophobic amino acid side chains and fatty acyl groups of phospholipids. In order to remove integral membrane proteins, the membrane must be disrupted by addition of detergents or other chaotropic reagents to solubilize the protein and to prevent aggregation and precipitation of the hydrophobic proteins upon their removal from the membrane. 

Wong and coworkers introduced an aromatic ring at the end of the fatty acyl chain [61,62]. They expected that their analogs would possess additional k-k stacking and some other specific interactions with aromatic amino acid residues Tyr73 or Trp40 at the bottom of the hydrophobic pocket of human CDld, leading to increased complex stability. 

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