Proteins lipophilic modifications

Lipophilic modifications. The covalent attachment of lipid moieties to proteins improves membrane binding capacity and/or certain protein-protein interactions. Among the most common lipophilic modifications are acylation (the attachment of fatty acids) and prenylation (Section 11.1). Although the fatty acid myristate (14 0) is relatively rare in eukaryotic cells, myristoylation is one of the most common forms of acylation. N-myristoylation (the covalent attachment of myristate by an amide bond to a polypeptide s amino terminal glycine residue) has been shown to increase the affinity of the a subunit of certain G proteins for membrane-bound j3 and y subunits. 

Posttranslational modification reactions prepare polypeptides to serve their specific functions and direct them to specific cellular or extracellular locations. Examples of these modifications include proteolytic processing (e.g., removal of signal proteins), glycosylation, methylation, phosphorylation, hydroxylation, lipophilic modifications (e.g., N-myristoylation and prenylation), and disulfide bond formation. 

Both of these groups are highly lipophilic and appear to play an important role in the binding of local anesthetics to the channel receptor proteins. Structural modification of this portion of the molecule has a profound effect on its physical and chemical properties, which in turn alters its local anesthetic properties. 

In 2003, Prior and others described methods for the extraction and analysis of hydrophilic and lipophilic antioxidants, using modifications of the ORAC procedure. These methods provide, for the first time, the ability to obtain a measure of total antioxidant capacity in the protein free plasma, using the same peroxyl radical generator for both lipophilic and hydrophilic antioxidants. This assay was also used to measure the total antioxidant capacity of guava fruit extracts (Thaipong and others 2006). 

Attractive Compounds. The female-produced sex pheromone of the yellow mealworm beetle, Tenebrio molitor, is (R)-4-methyl- 1-nonanol [316] 163 (Scheme 18). Careful investigations on the biosynthesis of this compound [317] revealed that it is produced through a modification of normal fatty acid biosynthesis (Fig. 1, Fig. 2) propanoate serves as the starter, while formal chain elongation with acetate, propanoate, and acetate (accompanied by removal of the oxygens) produces 4-methylnonanoate which yields the pheromone alcohol after reduction. The structures and role of proteins that are present in the hemolymph or secreted by the tubular accessory glands of T. molitor, and that may carry lipophilic chemical messengers (like pheromones) are under investigation [318,319]. 

The second approach involves chemical modification of the protein or peptide by attaching amphiphilic moieties composed of lipophilic alkyl groups and hydrophilic polyethylene glycol units to specific sites on the molecule.In addition to improving stability against enzymatic degradation, this modification is... 

Naturally occurring retinoids are characterized by three distinct structural elements (Fig. 7.1) (l)a lipophilic terminus composed of a j3-ionone ring, (2) an isoprene side chain that is subject to both enzymatic and non-en-zymatic isomerization (Fig. 7.2), and (3)a polar terminus that is the subject of oxidative modifications (Figs. 7.1 and 7.2). All of these processes occur in vivo with the superimposed complexity of a multitude of binding and transport proteins and receptors possessing differential affinities for these naturally occurring retinoids. 

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